2013-08-08T11:16:56-05:00 2013-03-31 521511275 Raffa PC 1899 L Street NW Suite 900 Washington DC 20036 990 2012-04-01 237337229 BrightFocus Foundation BRIG 3019483244 22512 Gateway Center Drive Clarksburg MD 20871 Stacy Pagos Haller 3019483244 2013-08-08 1 Frank H Smith P00639053 2028225000 2013-08-07 2012 2016-02-24 21:20:13Z Stacy Pagos Haller 22512 Gateway Center Drive Clarksburg MD 20871 27920319 0 X www.brightfocus.org X 1973 DC BrightFocus Foundation seeks to save sight and mind. 11 11 47 58 0 0 22601859 23534029 0 0 696172 614981 1111974 734020 24410005 24883030 5702962 7527500 0 0 3544993 3758245 379676 512040 5030353 11799045 11776521 21426676 23574306 2983329 1308724 39273122 42238889 13573560 14204661 25699562 28034228 X BrightFocus Foundation (BrightFocus)seeks to save mind and sight by funding innovative research worldwide and by promoting better health through education. BrightFocus is a nonprofit organization whose programs include Alzheimer's Disease Research, Macular Degeneration Research, and National Glaucoma Research. BrightFocus also promotes public education about these diseases including risk factors, preventative lifestyles, current treatments, and coping strategies.In FY 2013, BrightFocus awarded 55 new grants totaling $7.5 million to scientists conducting research on Alzheimer's, glaucoma and macular degeneration. 0 0 10253189 4538012 Alzheimer's Disease Research (ADR)-- ADR annually awards peer-reviewed grants to scientists from institutions worldwide who are conducting biomedical and clinical research on Alzheimer's disease. ADR grants fall into three categories. Standard and pilot awards are intended for established researchers; postdoctoral research fellowships support scientists who are training to assume the responsibilities of directing their first research laboratory. During the fiscal year ended March 31, 2013, ADR funded 25 new projects, totaling $4,538,012, and awarded $250,000 to one special project, a clinical trial to examine a potential new therapy for Alzheimer's disease. In addition, this year BrightFocus co-founded the 21st Century Brain Trust. This partnership of three non-profits made its first grant of $50,000, managed by BrightFocus, to fund a clinical trial testing opportunities for patient engagement in health through mobile health technologies. The projects range from advanced genetic studies that aim to identify inheritable risks for Alzheimer's disease through those designed to create new therapeutic interventions against the disease. Additional information about specific projects is included in Schedule I. BrightFocus continues to develop its partnership with the academic journal "Molecular Neurodegeneration" as the official journal of the BrightFocus Foundation. The journal publishes technical papers primarily on topics related to the ADR program. As an "open access" journal, there is no fee for readers, and all content is freely available through its website. This ensures maximal exposure of journal contents to scientists and care providers world-wide. ADR awards made national headlines in this fiscal year, including a high visibility reports suggesting roles for previously approved drugs cancer and diabetes drugs in combating Alzheimer's disease. Both areas of research are the subject of ongoing BrightFocus funded clinical trials. More details are available in the news updates section of the BrightFocus.org website.In addition to our research grant awards program, ADR provides information about risk factors, preventive measures, diagnosis, treatment, and lifestyle changes for Alzheimer's patients, their families, caregivers, at-risk groups, the media, and the public at large. The program also ensures that target audiences are aware of BrightFocus-funded research on Alzheimer's disease and the latest scientific developments. ADR provides this information through eAlerts, newsletters, social media, informational publications, videos, podcasts, and TV and radio public service announcements (PSAs). Medical and research news updates are routinely posted on the BrightFocus website and disseminated through print and electronic media.BrightFocus provides a number of printed patient education and public information materials. Most frequently requested among these publications is "Living with Alzheimer's Disease," a 35-page booklet with information including risk factors and mitigation, causes and treatment of the disease, coping and caregiving strategies, financial and legal planning, and resources for patients and families. Other materials, updated this year, include:1. "Understanding Alzheimer's: It's Not Just Forgetfulness" 2. "Care for the Caregiver: Managing Stress"3. "Safety and the Older Driver"4. "Staying Safe: Wandering and the Alzheimer's Patient" 5. 15 fact sheets6. 20 streaming video and audio programsADR publications (with the exception of newsletters) have also been translated into Spanish. All of the above-referenced materials are available in PDF on the BrightFocus website at www.brightfocus.org/ADRresources.In addition to the resources available on the website, 3 issues of the ADR newsletter were sent to thousands of people this year. An ADR PSA, "Now is the Moment to Stop Alzheimer's Disease," was produced in English and Spanish, and began running nationwide on TV and radio. ADR benefitted from $3,454,007 in donated media services and garnered 22,618,817 impressions. This informational PSA continues to generate calls, emails, and web visits from people affected by, or interested in, the disease. Members of BrightFocus's Scientific Affairs division served as sources for media. Stories were published by several media outlets during the year including National Public Radio, Politico, Voice of America, Medical Daily, Seattle Post-Intelligencer, and Rochester Post-Bulletin. BrightFocus also participated in TEDMED and National Press Club panels addressing Alzheimer's disease. BrightFocus increased its advocacy activity on Alzheimer's disease, gaining over 22,000 signatures on a Stop Alzheimer's Petition. BrightFocus released the results of our researcher survey in February, which revealed that a large majority of Foundation-funded scientists conducting brain or vision research believed that inadequate federal research funding was threatening a "brain drain" of talented researchers. ADR provided 194 answers to Ask an Expert questions during the year. This question-and-answer forum provides professionally researched answers to questions submitted to BrightFocus's ADR program. ADR distributed 35 medical and research eAlerts on Alzheimer's disease to ADR's listserv subscribers. Several messages on Alzheimer's disease were distributed weekly throughout the year on the BrightFocus social media channels, engaging thousands of followers. ADR mailed awareness-raising materials on Alzheimer's disease to hundreds of thousands of households, with messages focusing on: 1. Symptom recognition and steps the public should take, such as making an appointment with the doctor if any of these symptoms exist.2. Lifestyle choices that promote good health, encouraging readers to take action to reduce the likelihood of the onset of the disease (i.e. exercise your mind by playing board games, cards, and puzzles).3. Research results and treatments available to address Alzheimer's disease. 3649098 1440000 Macular Degeneration Research (MDR) -- Through an outreach effort in key trade publications and information distribution at major conferences for eye researchers, MDR encourages junior- and senior-level scientists around the world to apply for its prestigious research grant program. MDR annually offers grants to scientists through a sophisticated peer-review process managed by the MDR Scientific Review Committee. This group of the field's leading scientists bases these decisions on scientific merit using a rigorous evaluation system. During the fiscal year ending March 31, 2013, MDR awarded $1,440,000 in grants to 12 new projects that range from studies to understand the influence of racial identity on increased risk for macular degeneration to those aimed at designing new cell-based therapies to target and eliminate the molecular changes that lead to macular degeneration. Additional details about specific projects are included in Schedule I. MDR-funded projects were featured in media articles, including progress in the development of a molecular switch to replace dying photoreceptors, as well as progress in treating the currently untreatable dry for of macular degeneration. More details on this and other successful outcomes achieved through MDR funding are available in the news updates section of the BrightFocus.org website.MDR's Children's Corner for Macular Degeneration, a website aimed at teaching children and their families about the degenerative disease through stories, interactive games, and sharing activities, continues to help family members learn about the disease. The BrightFocus PSA titled "What Would You Like to See" aired as part of our "See a Better Tomorrow" campaign. Produced in English and Spanish, it was aired on TV, radio, and online, raising awareness about glaucoma and macular degeneration and generating calls, emails, and website visits. MDR benefitted from $6,272,112 in donated media services and garnered 348,171,590 impressions. MDR proactively disseminates information to the public directly and via traditional and social media. Other channels include email, newsletters, publications, videos, and podcasts. This includes information on risk factors, preventive measures, the progression of the disease, available medical treatments, suggestions for adapting to low vision, and new research developments. Medical and research news updates on macular degeneration are routinely posted on the BrightFocus website and distributed to interested audiences.MDR continued to distribute high quality informative materials, including updated editions of "Macular Degeneration: The Essential Facts," the comprehensive booklet "Living with Macular Degeneration," "Safety and the Older Driver," and the "Low Vision Resource List." MDR created a set of eight fact sheets in English and Spanish as well as new streaming media content. The organization now provides 13 macular degeneration videos, including an animated video series, donated by Eyemaginations. Three editions of the MDR newsletter were sent to interested constituents by mail and email. All MDR publications are in large print and available in PDF in English and Spanish on the BrightFocus website at www.brightfocus.org/MDRresources. The BrightFocus Insider Report, which included information about macular degeneration, was distributed twice this year. Answers to 253 Ask an Expert questions on macular degeneration were provided via email and on the BrightFocus website during the year. MDR distributed 14 medical and research eAlerts to the macular degeneration listserv subscribers. Each week BrightFocus distributed a range of messages on macular degeneration using its social media channels, engaging thousands of followers. BrightFocus Scientific Affairs division staff members were interviewed for media stories including several vision-oriented radio programs. The Miami Herald printed a letter to the editor from BrightFocus on the importance of comprehensive eye examinations in detecting macular degeneration. MDR mailed awareness-raising materials on macular degeneration to tens of thousands of households, with highlighted messages including: 1. Identifying symptoms and recommending steps the public can take, such as getting comprehensive eye exams regularly.2. Lifestyle choices that promote good health and reduce the likelihood of disease, like eating an "eye healthy" diet.3. Current research and the preventive measures that can be taken to help reduce the risk of macular degeneration. 1955748 1549488 National Glaucoma Research (NGR) -- NGR grants are available to glaucoma researchers worldwide. NGR places special emphasis on encouraging applications from young scientists and those with cutting-edge ideas. Annual grant applications are peer-reviewed, and recipient selections are based on scientific merit. During the fiscal year ending March 31, 2013, NGR awarded $1,549,488 for 16 new projects that range from examinations of the roots of glaucoma in the brain to studies designed to alleviate the buildup of pressure within the eye, a documented risk factor for glaucoma. Additional details about specific projects are included in Schedules F & I.NGR-funded research was recognized by the media this year, including new NGR-supported data that provide new genetic links that might control how glaucoma is passed from one generation to another. Other news reports detailed new BrightFocus supported strategies for protecting the nervous system of the eye from damage due to glaucoma. More details are available in the news updates section of the BrightFocus.org website.The NGR communications outreach program encourages people to take preventive measures (e.g., scheduling regular eye exams), to adhere to medication regimens, and to understand risk factors and symptoms. It also provides information on treatments as well as resources for adjusting to low vision. Regular updates on current glaucoma research and the latest study results are disseminated to the public directly and through the web, email, and social and traditional media. As a curator of critical news in the field, NGR distributed 12 medical and research eAlerts to its glaucoma listserv subscribers.NGR responded to 235 Ask an Expert questions, sending emails directly to the inquirers and posting answers on the website for all to see. Updated versions of two NGR publications--"Essential Facts on Glaucoma" and "Living with Glaucoma"--continue to be in great demand. Other popular publications include "Safety and the Older Driver," the new "Low Vision Resource List," and five glaucoma fact sheets in English and Spanish. All NGR materials are in large print and available in PDF in English and Spanish at www.brightfocus.org/NGRresources. The site also features 15 podcasts and 15 video series including a series of seven videos describing glaucoma risk factors, symptoms, diagnosis, treatments, lifestyle changes, and research. This video series, produced with the MonkeySee network, is available through more than 1500 online outlets as well as the BrightFocus site and YouTube. BrightFocus now delivers an animated video series about glaucoma through Eyemaginations. Three editions of the NGR newsletter were mailed to readers during the year and posted to the BrightFocus website, and information about glaucoma was included in two editions of the BrightFocus Insider Report. With one of the most active social media followings in the glaucoma field, NGR communicated news and information several times each week via these networking channels. The BrightFocus PSA titled "What Would You Like to See" aired as part of our "See a Better Tomorrow" campaign. Produced in English and Spanish, it ran on TV, radio, and the Internet, raising awareness about glaucoma and macular degeneration and generating calls, emails, and web visits. NGR benefitted from $6,272,112 in donated media services and garnered 348,171,590 impressions. BrightFocus's Scientific Affairs division staff members were interviewed for media stories including several vision-oriented radio programs. NGR mailed awareness-raising materials on glaucoma to tens of thousands of households, focusing on: 1. Symptom recognition, urging people to schedule an eye examination for early detection, as symptoms are not always noticed in early stages of the disease.2. Lifestyle choices that promote good health and steps the public can take to reduce the likelihood of the onset of the disease (i.e. eat an "eye healthy" diet).3. Treatments and medicines to control the disease and any actions that can be taken to assist people living with glaucoma and their families. 15858035 1 1 0 0 0 0 0 0 0 1 1 1 0 0 1 1 1 0 0 0 1 1 0 1 1 0 0 1 0 1 0 0 0 0 0 0 0 0 1 0 0 0 1 0 0 0 0 1 238 0 1 47 1 0 0 0 0 0 1 1 0 0 0 0 X 11 11 0 0 1 0 0 0 0 1 1 0 0 1 1 1 1 1 1 1 0 0 AK AL AR AZ CA CT FL GA HI IL KS KY ME MD MA MI MN MS NH NJ NM NY NC ND OH OK OR PA RI SC TN UT VA WA WV WI X X David F Marks CPA CMA 3019483244 22512 Gateway Center Drive Clarksburg MD 20871 Grace Frisone 16.00 X X 0 0 0 Michael H Barnett Esq 4.00 X X 0 0 0 Nicholas W Raymond 12.00 X X 0 0 0 Scott Rodgville CPA 5.00 X X 0 0 0 June Kinoshita 5.00 X 0 0 0 Judith Lee 5.00 X 0 0 0 Diane Marcello 3.00 X 0 0 0 Henry Pownall PhD 2.00 X 0 0 0 Brian K Regan PhD 4.00 X 0 0 0 Jonathan Rice Esq 3.00 X 0 0 0 Eltjo R Ed Schoonveld 3.00 X 0 0 0 Stacy Pagos Haller 55.00 X 342048 0 61835 Donna Callison 45.00 X 166130 0 34261 David F Marks CPA CMA 45.00 X 149545 0 40253 Melissa May 45.00 X 135129 0 24586 Guy Eakin Ph D 45.00 X 125441 0 47318 918293 0 208253 5 0 1 0 WildeLW Robbins Associates Inc 201 Summer Street Holliston MA 01746 Public awareness consul. & materials 4947108 Blackbaud Inc 2000 Daniel Island Drive Charleston SC 29492 Database management 291867 Global Technology Solutions Inc 2977 Stewart Loop Unit B Fort Meade MD 20755 Building & office services 162169 3 241804 26839 23265386 46049 23534029 528040 528040 231749 231749 564117 51857 512260 512260 512260 3049918 2962977 86941 86941 86941 12466 26839 22455 -9989 -9989 24883030 0 0 1349001 6678012 6678012 849488 849488 611734 243423 141891 226420 2316960 1185073 735158 396729 254688 130267 80811 43610 382601 195692 121397 65512 192262 98338 61003 32921 78628 11127 67501 79856 29331 18145 32380 512040 512040 131849 131849 468886 363142 44063 61681 594605 307855 191236 95514 568548 309411 165471 93666 347425 182868 113241 51316 166120 100086 34864 31170 108137 102517 2967 2653 273741 141818 86239 45684 74443 39607 21520 13316 Pub. awareness postage 3951007 2073016 295595 1582396 Pub. awareness printing 2606816 1372644 186416 1047756 Pub. awareness comp. 1097784 601012 77436 419336 List rental 678932 357162 45517 276253 549744 486146 63598 23574306 15858035 2685918 5030353 X 8723998 4267095 668563 3788340 3573854 3920291 436317 1418430 5583310 5336038 239858 176008 18768 19646 180776 104897 10986498 2383676 8707935 8602822 17214019 19464859 2230062 2364446 1088223 831452 39273122 42238889 711208 584225 10348020 11924959 841601 0 1672731 1695477 13573560 14204661 X 12246014 15916258 13363548 12027970 90000 90000 25699562 28034228 39273122 42238889 X 1308724 1019596 6346 X 0 1 X 1 0 X 19950796 21879337 18261062 22601859 23511574 106204628 19950796 21879337 18261062 22601859 23511574 106204628 106204628 1512451 1572008 1443239 1345423 1323906 7197027 2303 1132 14 16 3465 113405120 37705 0.93650 0.93150 X RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED 90000 2316 2316 90000 90000 1312 1312 90000 90000 3792 3792 90000 90000 3715 3715 90000 90000 4009 4009 90000 0.00000 1.00000 0.00000 1 0 2800000 1147363 3947363 1629400 4604427 1856600 4377227 628501 361511 266990 176807 165565 11242 8602822 Alternative investments - partnership 2364446 F 2364446 Charitable gift annuities 1537755 Rental deposits 80000 Capital lease obligations 77722 1695477 X 41831950 1019596 15998231 21163 17038990 24792960 131849 -41779 90070 24883030 39497284 15998231 14817 16013048 23484236 131849 -41779 90070 23574306 Description of Intended Use of Endowment Funds: Part V, Line 4: The earnings on this endowment are available for the Alzheimer's Disease Research program and are recorded as temporarily restricted investment income and are released as spent. Description of Uncertain Tax Positions Under FIN 48: Part X, Line 2: BrightFocus has adopted the guidance under FASB ASC Topic 740, Income Taxes, related to accounting for uncertainty in income taxes. BrightFocus management believes that BrightFocus has no material uncertain tax positions and, accordingly, it will not recognize any liability for unrecognized taxes. Part XI, Line 4b - Other Adjustments: Depreciation on rental property -41,779. Part XII, Line 2d - Other Adjustments: Special event service expenses 13,492. Change in present value of grants 1,325. Part XII, Line 4b - Other Adjustments: Depreciation on rental property -41,779. 1 East Asia and the Pacific 0 0 Grantmaking 319488 Europe (Including Iceland & Greenland) 0 0 Grantmaking 220000 Middle East and North Africa 0 0 Grantmaking 310000 0 0 0 0 0 0 849488 0 849488 Middle East and North Africa Alzheimer's Disease Reasearch by Avraham Zangen, PhD Entitled: (A2013395S) 190000 Wire transfer Europe (Including Iceland & Greenland) National Glaucoma Research by Darryl Overby,PhD Entitled: (G2013048) 100000 Wire transfer East Asia and the Pacific National Glaucoma Research by John Wood, DPhil Entitled: (G2013135) 100000 Wire transfer East Asia and the Pacific National Glaucoma Research by Alex Hewitt, PhD Entitled: (G2013136) 99488 Wire transfer Middle East and North Africa Macular Degeneration Research by Ruth Ashery-Padan, PhD Entitled: (M2013065) 120000 Wire transfer East Asia and the Pacific Macular Degeneration Research by Chi Luu, PhD Entitled: (M2013111) 120000 Wire transfer Europe (Including Iceland & Greenland) Macular Degeneration Research by Sarah Doyle, PhD Entitled: (M2013129) 120000 Wire transfer 7 0 0 0 0 0 0 0 Procedure for Monitoring Grants Outside the U.S.: Schedule F, Part I, Line 2: BrightFocus interacts with all grantees at least quarterly by e-mail or at scientific meetings. In addition to these interactions, each grant recipient is required to submit separate detailed annual Scientific Progress and Financial Reports to BrightFocus. These are received by the BrightFocus Scientific Affairs department, and reviewed by scientific staff with broad expertise in molecular biology, cell biology, biochemistry, imaging and genetics. Senior staff reviews each Progress Report and evaluates the project for sufficient progress towards the specific aims proposed in the original application or any budgetary concerns. This effort is supported by additional scientific counsel from members of the BrightFocus Scientific Review Committees when required. In addition to statements of experimental progress, all grantees are asked to report any technical publications, media reports, or patent applications in which BrightFocus sponsored research is described. If significant concerns related to progress on the awards are discovered, the BrightFocus staff recommends appropriate actions to the Chair of the Board of Directors Grants Committee. The Scientific Affairs senior staff is empowered to authorize the withholding of funding, or discontinuation of awards, for any grantees that fail to achieve sufficient progress or fail to submit required reports. At the conclusion of the grant award period each grantee must complete and submit a Final Report that is also reviewed by the BrightFocus senior scientific staff. Evaluation of the work of each grantee is qualitatively and quantitatively assessed through various metrics related to impact of the grant on its targeted disease field. Such impact metrics have revealed that 95% of BrightFocus supported research results in research publications that advance the fields served by BrightFocus. This impact is further supported by annual citation analysis that compares BrightFocus supported works to a statistical sample of works supported by either the US Federal Government or that of other funding agencies. BrightFocus supported publications are consistently cited at nearly twice the frequency of any other comparison group. A final example of impact assessment revealed that the successes of BrightFocus grantees continue long after the grant expires. On average, each grantee receives 2.2 additional grants for projects spawned by the BrightFocus grant. These come at values nearly 10 times the level of the initial BrightFocus investment. BrightFocus solicits feedback from its grantees, and provides an anonymous forum for collecting such information. The Final Report package includes a page to be detached and anonymously mailed to the Scientific Affairs department. This document requests an assessment of the grantee experience as a BrightFocus awardee. Any suggestions, concerns, complaints, or positive experiences can be outlined and brought to the attention of BrightFocus on this form so that BrightFocus can address any areas needing improvement, reaffirm praise-worthy policies, or otherwise assess needs for programmatic change. The senior Scientific Staff present and summarize the status and progress on all grants to the BrightFocus Board of Directors at each of their quarterly Board Meetings. X X X X X X 1 WildeLW Robbins Associates Inc 201 Summer Street Holliston MA 07146 Fundraising and communications consultant 0 15025664 960889 14064775 Strategic Fundraising Inc 7800 3rd Street North Suite 900 St Paul MN 55128 Telemarketing 0 64262 80291 -16659 PDR II Inc 79 Chapel Street Newton MA 02458 Telemarketing 0 11011 19974 -8963 15100937 1061154 14039153 AL AK AZ AR CA CO CT DC FL GA HI IL KS KY LA ME MD MA MI MN MS MO NH NJ NM NY NC ND OH OK OR PA RI SC TN UT VA WA WV WI Golf Tournament 39305 26839 12466 482 1401 8610 3932 8030 39305 26839 12466 482 1401 8610 3932 8030 22455 -9989 Explanation of Fundraising Payments Schedule G, Part I, Line 2b, Column (v) In the contract with Wilde/LW Robbins Associates, Inc., the management fees are fixed amounts per month for in-scope services. Work performed out of the scope of fundraising counsel services are approved by BrightFocus before they are performed and paid. 1 Massachusetts General Hospital 55 Fruit Street Boston MA 02114 041564655 501(c)(3) 100000 Alzheimer's Disease Reasearch by Jasmeer Chhatwal, MD, PhD Entitled: (A2013003F) University of California San Diego 9500 Gilman Drive La Jolla CA 92093 956006144 501(c)(3) 100000 Alzheimer's Disease Reasearch by Jessica Young, PhD Entitled: (A2013022F) Massachussetts Institute of Technology 77 Massachusetts Avenue Cambridge MA 02139 042103594 501(c)(3) 100000 Alzheimer's Disease Reasearch by Adam Bero, PhD Entitled: (A2013026F) New York University 4 Washington Place New York NY 10003 135562308 501(c)(3) 100000 Alzheimer's Disease Reasearch by Tao Ma, MD, PhD Entitled: (A2013030F) Washington University 660 S Euclid Avenue St Louis MO 63110 430653611 501(c)(3) 100000 Alzheimer's Disease Reasearch by Fan Liao, PhD Entitled: (A2013037F) Albert Einstein College of Medicine 1300 Morris Park Avenue Bronx NY 10461 132937352 501(c)(3) 100000 Alzheimer's Disease Reasearch by Dolores Del Prete, PhD Entitled: (A2013046F) Brigham and Women's Hospital 75 Francis Street Boston MA 02215 042312909 501(c)(3) 250000 Alzheimer's Disease Reasearch by Dominic Walsh, PhD Entitled: (A2013059S) Massachusetts General Hospital 55 Fruit Street Boston MA 02114 041564655 501(c)(3) 100000 Alzheimer's Disease Reasearch by Se Hoon Choi, PhD Entitled: (A2013140F) Mayo Clinic Jacksonville 4500 San Pablo Road South Jacksonville FL 32224 593337028 501(c)(3) 250000 Alzheimer's Disease Reasearch by Nilufer Ertekin-Taner, MD, PhD Entitled: (A2013157S) The Curators of the University of Missouri 319 Jesse Hal Columbia MO 65211 436003859 501(c)(3) 250000 Alzheimer's Disease Reasearch by Laurie Erb, PhD Entitled: (A2013171S) Yale University 333 Cedar Street New Haven CT 06520 060646973 501(c)(3) 250000 Alzheimer's Disease Reasearch by Stephen Strittmatter, MD, PhD Entitled: (A2013184S) Boston University 85 East Newton Street M-921 Boston MA 02215 042103547 501(c)(3) 250000 Alzheimer's Disease Reasearch by David Harris, MD, PhD Entitled: (A2013245S) The Cleveland Clinic Foundation 9500 Euclid Avenue Cleveland OH 44195 340714553 501(c)(3) 100000 Alzheimer's Disease Reasearch by Crystal Miller, B.S., PhD Entitled: (A2013252F) Cedars-Sinai Medical Center 8700 Beverly Boulevard AHSP Los Angeles CA 90048 951644600 501(c)(3) 250000 Alzheimer's Disease Reasearch by Maya Koronyo, PhD Entitled: (A2013328S) Boston University 85 East Newton Street M-921 Boston MA 02215 042103547 501(c)(3) 100000 Alzheimer's Disease Reasearch by Hirohide Asai, MD, PhD Entitled: (A2013329F) Washington University 660 S Euclid Avenue St Louis MO 63110 430653611 501(c)(3) 248172 Alzheimer's Disease Reasearch by Carlos Cruchaga, PhD Entitled: (A2013359S) Michigan State University 775 Ball Avenue NE Grand Rapids MI 49503 386005984 501(c)(3) 250000 Alzheimer's Disease Reasearch by Lester Binder, PhD Entitled: (A2013364S) Baylor College of Medicine One Baylor Plaza Houston TX 77030 741613878 501(c)(3) 100000 Alzheimer's Disease Reasearch by Hongmei Li, PhD Entitled: (A2013370F) University of California Davis One Shields Avenue Davis CA 95616 946036494 501(c)(3) 250000 Alzheimer's Disease Reasearch by Lee-Way Jin, MD, PhD Entitled: (A2013414S) Massachusetts General Hospital 55 Fruit Street Boston MA 02114 041564655 501(c)(3) 100000 Alzheimer's Disease Reasearch by Vivek Gautam, PhD Entitled: (A2013478F) University of Florida 219 Grinter Hall Gainesville FL 32611 596002052 501(c)(3) 249840 Alzheimer's Disease Reasearch by Paramita Chakrabarty, PhD Entitled: (A2013504S) The University of Texas Southwestern Medical Center at Dallas 5323 Harry Hines Boulevard Dallas TX 75390 746000203 501(c)(3) 150000 Alzheimer's Disease Reasearch by Joachim Herz, MD Entitled: (A2013524S) Mayo Clinic Jacksonville 4500 San Pablo Road South Jacksonville FL 32224 593337028 501(c)(3) 250000 Alzheimer's Disease Reasearch by Leonard Petrucelli, PhD Entitled: (A2013546S) Columbia University Medical Center 630 West 168th Street New York NY 10032 133901821 501(c)(3) 50000 Alzheimer's Disease Reasearch by Ismael Santa-Maria Perez, PhD Entitled: (A2013555F) Massachusetts General Hospital 55 Fruit Street Boston MA 02114 041564655 501(c)(3) 50000 Alzheimer's Disease Reasearch by Bradley Hyman, MD, PhD Entitled: (A2013 21st CBT) Alzheimer's Drug Discovery Foundation 57 West 57th Street Suite 904 New York NY 10019 201082179 501(c)(3) 250000 Alzheimer's Disease Reasearch Entitled: (C2013999) Northwestern University 750 N Lake Shore Drive Chicago IL 60611 362167817 501(c)(3) 50000 National Glaucoma Research by Matthew Glucksberg, PhD Entitled: (G2013044) Temple University 3500 North Broad Street Philadelphia PA 19140 231365971 501(c)(3) 100000 National Glaucoma Research by Yang Hu, MD, PhD Entitled: (G2013046) Board of Regents of the University of Wisconsin System 21 N Park Street Madison WI 53715 396006492 501(c)(3) 100000 National Glaucoma Research by Curtis Brandt, PhD Entitled: (G2013050) Johns Hopkins University 720 Rutland Avenue Baltimore MD 21205 520595110 501(c)(3) 100000 National Glaucoma Research by Zhenhua Xu, PhD Entitled: (G2013058) University of Pittsburgh 4200 Fifth Avenue Pittsburgh PA 15213 250965591 501(c)(3) 100000 National Glaucoma Research by Kevin Chan, PhD Entitled: (G2013077) Regents of the University of Michigan 3003 South State Street Ann Arbor MI 48109 386006309 501(c)(3) 100000 National Glaucoma Research by Philip Gage, PhD Entitled: (G2013084) University of Oklahoma Health Sciences Center 608 Stanton L Young Boulevard Oklahoma City OK 73104 736097060 501(c)(3) 100000 National Glaucoma Research by Michael Elliott, PhD Entitled: (G2013092) University of Iowa 6-430 Bowen Science Building Iowa City IA 52242 421143702 501(c)(3) 100000 National Glaucoma Research by John Fingert, MD, PhD Entitled: (G2013103) University of Miami Miller School of Medicine 1601 Northwest 12th Avenue Miami FL 33136 590624458 501(c)(3) 100000 National Glaucoma Research by Kenneth Muller, PhD Entitled: (G2013107) University of Illinois Medical Center 1855 W Taylor Street Chicago IL 60612 376000511 501(c)(3) 100000 National Glaucoma Research by Beatrice Yue, PhD Entitled: (G2013110) University of Miami-Bascom Palmer Eye Institute 900 NW 17th Street Miami FL 33136 590624458 501(c)(3) 100000 National Glaucoma Research by Richard Lee, MD, PhD Entitled: (G2013121) Weill Medical College of Cornell University 525 E 68th Street New York NY 10021 150532082 501(c)(3) 100000 National Glaucoma Research by Anna Demetriades, MD, PhD Entitled: (G2013141) Hunter College CUNY 695 Park Avenue New York NY 10065 133893536 501(c)(3) 100000 National Glaucoma Research by Hyungsik Lim, PhD Entitled: (G2013143) Tulane University 6400 Freret Street New Orleans LA 70118 720423889 501(c)(3) 120000 Macular Degeneration Research by Shusheng Wang, PhD Entitled: (M2013007) Children's Hospital Boston Harvard Medical School 300 Longwood Avenue Boston MA 02115 042103580 501(c)(3) 120000 Macular Degeneration Research by Jing Chen, PhD Entitled: (M2013041) University of California Riverside 900 University Avenue Riverside CA 92521 956006142 501(c)(3) 120000 Macular Degeneration Research by Dimitrios Morikis, PhD Entitled: (M2013106) University of Pennsylvania School of Medicine 3451 Walnut Street Philadelphia PA 19104 231352685 501(c)(3) 120000 Macular Degeneration Research by Venkata Chavali, PhD Entitled: (M2013122) Harvard Medical School 25 Shattuck Street Boston MA 02215 042103580 501(c)(3) 120000 Macular Degeneration Research by Chenghua Gu, DVM, PhD Entitled: (M2013127) University of Oklahoma Health Sciences Center 608 Stanton L Young Boulevard Oklahoma City OK 73104 736097060 501(c)(3) 120000 Macular Degeneration Research by Martin-Paul Agbaga, PhD Entitled: (M2013130) Weill Medical College of Cornell University 525 E 68th Street New York NY 10021 150532082 501(c)(3) 120000 Macular Degeneration Research by Marcelo Nociari, PhD Entitled: (M2013146) University of California San Diego 9500 Gilman Drive La Jolla CA 92093 956006144 501(c)(3) 120000 Macular Degeneration Research by Jonathan Lin, MD, PhD Entitled: (M2013158) The Schepens Eye Research Institute 20 Staniford Street Boston MA 02114 256638196 501(c)(3) 120000 Macular Degeneration Research by Magali Saint-Geniez, PhD Entitled: (M2013161) 48 0 Procedure for Monitoring Grants in the U.S.: Part I, Line 2: Schedule I, Part I, Line 2: BrightFocus interacts with all grantees at least quarterly by e-mail or at scientific meetings. In addition to these interactions, each grant recipient is required to submit separate detailed annual Scientific Progress and Financial Reports to BrightFocus. These are received by the BrightFocus Scientific Affairs department, and reviewed by scientific staff with broad expertise in molecular biology, cell biology, biochemistry, imaging and genetics. Senior staff reviews each Progress Report and evaluates the project for sufficient progress towards the specific aims proposed in the original application or any budgetary concerns. This effort is supported by additional scientific counsel from members of the BrightFocus Scientific Review Committees when required. In addition to statements of experimental progress, all grantees are asked to report any technical publications, media reports, or patent applications in which BrightFocus sponsored research is described. If significant concerns related to progress on the awards are discovered, the BrightFocus staff recommends appropriate actions to the Chair of the Board of Directors Grants Committee. The Scientific Affairs senior staff is empowered to authorize the withholding of funding, or discontinuation of awards, for any grantees that fail to achieve sufficient progress or fail to submit required reports. At the conclusion of the grant award period each grantee must complete and submit a Final Report that is also reviewed by the BrightFocus senior scientific staff. Evaluation of the work of each grantee is qualitatively and quantitatively assessed through various metrics related to impact of the grant on its targeted disease field. Such impact metrics have revealed that 95% of BrightFocus supported research results in research publications that advance the fields served by BrightFocus. This impact is further supported by annual citation analysis that compares BrightFocus supported works to a statistical sample of works supported by either the US Federal Government or that of other funding agencies. BrightFocus supported publications are consistently cited at nearly twice the frequency of any other comparison group. A final example of impact assessment revealed that the successes of BrightFocus grantees continue long after the grant expires. On average, each grantee receives 2.2 additional grants for projects spawned by the BrightFocus grant. These come at values nearly 10 times the level of the initial BrightFocus investment. BrightFocus solicits feedback from its grantees, and provides an anonymous forum for collecting such information. The Final Report package includes a page to be detached and anonymously mailed to the Scientific Affairs department. This document requests an assessment of the grantee experience as a BrightFocus awardee. Any suggestions, concerns, complaints, or positive experiences can be outlined and brought to the attention of BrightFocus on this form so that BrightFocus can address any areas needing improvement, reaffirm praise-worthy policies, or otherwise assess needs for programmatic change. The senior Scientific Staff present and summarize the status and progress on all grants to the BrightFocus Board of Directors at each of their quarterly Board Meetings. X X X X X 0 0 0 0 0 0 0 1 0 Stacy Pagos Haller 300100 0 40000 0 1948 0 25000 0 36835 0 403883 0 0 0 Donna Callison 164546 0 0 0 1584 0 14770 0 19491 0 200391 0 0 0 David F Marks CPA CMA 148993 0 0 0 552 0 22709 0 17544 0 189798 0 0 0 Melissa May 134577 0 0 0 552 0 7425 0 17161 0 159715 0 0 0 Guy Eakin Ph D 125225 0 0 0 216 0 19508 0 27810 0 172759 0 0 0 Part I, Line 3 Before approving the compensation of the President/CEO, the Board determines the total compensation to be provided by BrightFocus to the President/CEO is reasonable in light of the position, responsibility and qualification of the position held including the result of an evaluation of prior performance for BrightFocus, if applicable. The President/CEO is evaluated annually by the Board of Directors through the use of an in-depth goal attainment structure, (developed with advice from Board Source) that includes a self assessment and a Board of Directors assessment and evaluation against set goals, outcomes and deliverables. The Board of Directors obtains and considers appropriate data, including a salary survey, which includes information compiled from the federal Form 990 of other organizations, concerning compensation paid to President/CEOs in like circumstances. In making the determination, the Board of Directors shall consider total compensation to include the salary and value of all benefits provided by BrightFocus to the individual in payment for services. At the time of the BrightFocus Board discussion and decision concerning the President/CEO's compensation, the President/CEO is not present in the meeting. Part I, Line 7 As the President/CEO's bonus was not a fixed payment specified in her employment contract, this item has been answered 'yes' in accordance with the Internal Revenue Service instructions. However, it should be noted that BrightFocus believes her bonus was a non-fixed payment based on our internal procedures. The Board of Directors considers the award of a discretionary bonus each year. The determination of the bonus compensation is capped as specified in her employment contract, and if not warranted will not be awarded at all. The determination is made by the full Board upon recommendation of its Compensation Committee. The Compensation Committee considers a set of goals for the President/CEO's performance developed at the beginning of the year in consultation with the President/CEO. Each goal is evaluated at the end of the fiscal year to determine whether the goal has been met or exceeded. The bonus is awarded based on a detailed review by the Board of Directors of whether each goal has been met or exceeded. X 10 37086 FMV X Special events 1 8963 FMV 0 1 0 Form 990, Part VI, Section A, line 4 The Board of Directors voted to change the legal name of the organization to BrightFocus Foundation and amend all organizational documents to reflect this change. BrightFocus filed with the District of Columbia a certificate of amendment to its articles of incorporation changing its name from American Health Assistance Foundation to BrightFocus Foundation. In addition, BrightFocus requested and obtained from the Internal Revenue Service an updated exempt organization determination letter that reflects the name BrightFocus Foundation. Form 990, Part VI, Section B, line 11 A draft of the federal Form 990 shall be distributed to the Audit Committee for review prior to being submitted to the Internal Revenue Service. The draft federal Form 990 shall be distributed early enough to provide each Committee member with a reasonable amount of time for review and submission of questions or comments prior to the filing deadline. The final federal Form 990 shall be distributed to each Board member prior to being filed with the Internal Revenue Service. The draft and final Form 990 may be distributed in person, by regular mail, e-mail, or fax. Form 990, Part VI, Section B, line 12c BrightFocus has all employees, officers, and directors agree to the code of conduct that includes adherence to the Conflict of Interest and Implementation Policy. Each board director, officer, and employee is required annually to complete a conflict of interest disclosure statement, which is thereafter reviewed by BrightFocus's chief compliance officer. If a conflict is reported it is then referred to BrightFocus's legal counsel and, if appropriate and necessary, then to the Board of Directors or its appointed Committee for further action. Although a person with a potential or actual conflict may provide factual information to the Board and respond to the Board's questions, he or she may not participate in the discussion or decision of a proposed transaction or matter. The conflicted person shall recuse him/herself from the deliberation process, and leave the meeting. Form 990, Part VI, Section B, line 15a The BrightFocus Foundation (BrightFocus) Board of Directors has overall authority and responsibility for approving the annual budget which includes compensation for all employees at every level including non-director officers. All pay adjustments are made on a yearly basis effective April 1st, the beginning of the BrightFocus fiscal year. Before approving the compensation of the CEO, the Board determines the total compensation to be provided by BrightFocus to the CEO is reasonable in light of the position, responsibility and qualification of the position held including the result of an evaluation of prior performance for the Foundation, if applicable. The CEO is evaluated annually by the Board through the use of an in-depth goal attainment structure, (developed with advice from Board Source) that includes a self assessment and Board assessment and evaluation against set goals, outcomes and deliverables. The Board obtained and considered appropriate data, including a salary survey, which included information compiled from the Form 990 of other organizations, concerning compensation paid to CEOs in like circumstances. In making the determination, the Board shall consider total compensation to include the salary and value of all benefits provided by BrightFocus to the individual in payment for services. At the time of the BrightFocus Board discussion and decision concerning the CEOs compensation, the CEO is not present in the meeting. The Board shall set forth the basis for its decisions with respect to compensation in the minutes of the meeting at which the decisions are made, including the conclusions of the evaluation and the basis for determining that the individual's compensation was reasonable in light of the evaluation and comparability data. Form 990, Part VI, Section C, line 19 BrightFocus makes its governing documents including its articles of incorporation and bylaws, conflict of interest policy, audited financial statements and federal Form 990 available to the public upon request. In addition, the public also has access to the annual report, the federal Form 1023, audited financial statements, the 501(c)(3) letter of determination from the Internal Revenue Service, and federal Form 990 on the BrightFocus website. Changes in Net Assets or Fund Balances: Form 990, Part XI, line 9: Recoveries of prior year grants 21,163. Change in present value of grants -1,325. Special events service expenses -13,492. Schedule F, Part II, Line 1, Column D: Region: (D) Purpose of Grant: Alzheimer's Disease Reasearch by Avraham Zangen, PhD Entitled: (A2013395S) Clinical Study of Deep-rTMS Treatment in Alzheimer's. Investigators Summary: Existing medications to Alzheimer Disease provide no cure and only very modest effects on cognition and on daily functioning. Recent technological achievements provide a way to induce electrical activity in deep brain regions without actually delivering electrical currents through the skull and body. This may help us to stimulate certain brain areas that are affected by Alzheimer and maybe to restore some of the lost cognitive ability or to delay deterioration. We will also record brain activity during treatments and learn about the ways that stimulation changes brain functioning and enhance cognition. Grant Awarded: $190,000, Ben-Gurion University of the Negev, Beer Sheva, Israel Region: (D) Purpose of Grant: National Glaucoma Research by Darryl Overby,PhD Entitled: (G2013048) Role of PLVAP in Regulation of Aqueous Outflow Facility. Investigators Summary: Glaucoma is a blinding eye disease associated with elevated pressure in the eye, and all treatments for glaucoma attempt to reduce eye pressure to prevent further vision loss. Our project investigates how eye pressure is regulated, focusing on a single of layer of cells that create a porous barrier to fluid drainage from the eye. In glaucoma, there are too few pores in this cell barrier, such that fluid drainage is partly blocked and pressure builds. By studying the factors controlling pore formation, we hope to one day exploit this process to induce pore formation as a way to enhance drainage and more successfully lower IOP in glaucoma. Grant Awarded: $100,000, Imperial College, London, England Region: (D) Purpose of Grant: National Glaucoma Research by John Wood, DPhil. Entitled: (G2013135) Does the Microtubule-Severing Enzyme Katanin Play a Role in the Pathogenesis of Glaucoma? Investigators Summary: The protein, tau, is known to be altered in Alzheimer's Disease causing the formation of neurofibrillary tangles which impair nerve function and contribute to brain damage in this condition. We believe that this process also occurs in the eye in glaucoma patients. By investigating whether tau is altered in models of glaucoma and whether altering this protein directly can cause a glaucoma-like condition, we will understand the role that this protein plays in this blinding disease. Also, by blocking action of the enzyme katanin, to see if this approach prevents glaucoma-like nerve damage, we will both further understand whether tau plays an important role in this disease and be able to treat glaucoma patients with a view to preventing these patients losing their vision. Grant Awarded: $100,000,South Australian Institute of Ophthalmology, Adelaide, Australia Region: (D) Purpose of Grant: National Glaucoma Research by Alex Hewitt, PhD Entitled: (G2013136) Refinement of an Induced Pluripotent Stem Cell model for Retinal Ganglion Cell Apoptosis. Investigators Summary: In the past two years we have made important genetic discoveries, which have dramatically improved our understanding of how glaucoma develops. From our discovery people who are at least three times more likely to develop glaucoma can be rapidly identified. We are now working to further understand how these genes cause disease in individual patients. This technique has become recently possible due to breakthroughs in stem cell technology enabling us to produce stem cells from adult tissue. This means we can examine the development of a disease in tissue, such as the retina, which cannot be easily obtained from a living person. We are using this technique to uncover the pathways for glaucoma, by comparing retinal ganglion cells generated from patients with differing genetic risk profiles. The application of this methodology is innovative and will hopefully lead to new therapies. Grant Awarded: $99,488, Centre for Eye Research Australia, The University of Melbourne, Melbourne, Australia Region: (D) Purpose of Grant: Macular Degeneration Research by Ruth Ashery-Padan, PhD Entitled: (M2013065)Roles for RPE-specific MicroRNAs in Age-related Retinal Diseases. Investigators Summary: Age-related macular degeneration (AMD) is a multifactorial disease, associated with a combination of genetic and environmental factors. The early stages of AMD involve dysfunction of the Retinal pigmented epithelium (RPE) in processes related to adhesion, protection against oxidative damage, triggering of the immune response and regulation of angiogenesis of the choriocapillaris. MicroRNAs (miRNAs) are a large group of small RNA molecules that have been recently identified to inhibit the expression of many genes simultaneously. Thus miRNAs are implicated in controlling a wide range of physiological and pathological events. In the course of this study, we will identify the involvement of miRNAs in processes that are altered in AMD. We will employ a combination of genetic, cellular, biochemical and molecular techniques that will enable us to reveal the involvement of miRNAs in AMD and other degenerative diseases of the retina. Grant Awarded: $120,000,Tel Aviv University, Tel Aviv, Israel. Region: (D) Purpose of Grant: Macular Degeneration Research by Chi Luu, PhD Entitled: (M2013111) Improved Characterization of Early AMD Phenotype by Combining Novel Imaging, Physiological Markers and Genotypes. Investigators Summary: This study aimed to develop realistic and effective diagnostic tests to identify individuals at risk of developing visual loss due to AMD. The results from this study will be crucial in the development of effective diagnostics and therapeutics in an emerging world of personalized medicine where different treatment strategies will be required for distinctly different risk groups of AMD. Grant Awarded: $120,000, Centre for Eye Research Australia, The University of Melbourne, Melbourne,Australia. Region: (D) Purpose of Grant: Macular Degeneration Research by Sarah Doyle, PhD Entitled: (M2013129) Investigating a Role for Toll Like Receptor 2 Signaling in the Pathogenesis of Age-Related Macular Degeneration. Investigators Summary: The first clinical sign that an individual has Age-related-macular-degeneration (AMD) is the presence of yellowish deposits, which accumulate in the area at the back of the eye known as the macula. The macula is responsible for your central vision; holding two coins in front of your eyes results in a single large black circle blocking your central vision, this is a realistic simulation of what it is like to live with the advanced disease. Typically, inflammatory responses of the immune system are caused as a result of microbial infection, however, in chronic conditions, a form of "sterile" inflammation can exist in areas of the body in response to damaged "self-elements", in the absence of infection, due to uncontrolled activation of the sensors of the immune response. We have found that this "sterile" inflammation is central to the course of AMD and we wish to investigate the pathways involved further with a view to discovering new treatments for AMD. Grant Awarded: $120,000, Trinity College, Dublin, Ireland Schedule I, Part II, Line 1, Column (H): Name of organization or government: Massachusetts General Hospital (H) Purpose of Grant or Assistance: Alzheimer's Disease Reasearch by Jasmeer Chhatwal, MD, PhD Entitled: (A2013003F) Cortical Network Disruption in Aging, Autosomal Dominant and Late-onset Alzheimer's Disease. Investigator's Summary: The purpose of this study is to use an advanced brain imaging technique to understand how aging and Alzheimer's disease degrade the brain networks that allow us to form and recall memories. These studies will help tell us how aging and Alzheimer's disease differ, and allow us to better design clinical trials in Alzheimer's disease. Also, these studies will help us understand why even older people without Alzheimer's disease may have memory problems as they age, a phenomenon some call "age-related cognitive decline". Name of organization or government: University of California, San Diego (H) Purpose of Grant or Assistance: Alzheimer's Disease Reasearch by Jessica Young, PhD Entitled: (A2013022F) Dissecting the Role of Individual Genetic Background in Sporadic Alzheimer's Disease. Investigator's Summary: Alzheimer's disease affects a significant portion of the elderly population and in most cases the reason why people develop the disease is unknown. The goal of my proposal is to ask whether common sequence differences in a patient's genome can predispose someone to a higher risk of developing Alzheimer's disease. I will do this by using human induced pluripotent stem cells, which are cells from adult tissue that are reprogrammed to have the capacity to generate every cell type of the body including nerve cells. Using these stem cells from AD patients with certain identified risk sequences, I will test whether the presence of these sequences lead to differences we can measure in the laboratory. Name of organization or government: Massachussetts Institute of Technology (H) Purpose of Grant or Assistance: Alzheimer's Disease Reasearch by Adam Bero, PhD Entitled: (A2013026F) Epigenetic Mechanisms of Memory Dysfunction in Alzheimer's Disease. Investigator's Summary: Memory impairment is a hallmark feature of Alzheimer's disease (AD), but the mechanisms that cause memory impairment in AD remain unclear. In this proposal, I will determine whether AD pathology prevents gene activation during memory formation. In addition, I will determine whether restoring the activity of neural circuits damaged by AD restores gene activation and improves memory performance. These experiments will fundamentally advance our understanding of what causes memory impairment in AD and will reveal novel treatment strategies for treating AD. Name of organization or government: New York University (H) Purpose of Grant or Assistance: Alzheimer's Disease Reasearch by Tao Ma, MD, PhD Entitled: (A2013030F) Reversing Alzheimer's Disease-associated Impairments of Synaptic Plasticity and Memory by Targeting AMP-activated Protein Kinase. Investigator's Summary: Currently, over 5 million Americans have Alzheimer's disease (AD) and the number is estimated to rise dramatically in the next few decades. Unfortunately, until now there is no therapy/drug available to cure or slow down the process of AD. This project will help understand the role of an important signaling pathway (AMPK) that is abnormal in AD, thus translate into novel therapeutic targets for AD and related cognitive syndromes. Name of organization or government: Washington University (H) Purpose of Grant or Assistance: Alzheimer's Disease Reasearch by Fan Liao, PhD Entitled: (A2013037F) Apolipoprotein E passive Immunotherapy for Alzheimer's Disease. Investigator's Summary: One of the main pathological hallmarks of Alzheimer disease is the deposition of amyloid beta in plaques in the extracellular space of the brain. We have developed a new passive immunization approach targeting apolipoprotein E, a protein that interacts with amyloid to influence its clearance and aggregation, to reduce the amyloid plaques in the brain. In this project, we will further explore the timing of intervention, the potential side effects, and the underlying mechanism of this approach. Name of organization or government: Albert Einstein College of Medicine (H) Purpose of Grant or Assistance: Alzheimer's Disease Reasearch by Dolores Del Prete, PhD Entitled: (A2013046F) Searching the Main Actors Involved in Human Dementia. Investigator's Summary: Mutations in genes that regulate the processing of APP cause Familial Dementias in humans. BRI2 is one of these genes. We have generated a mouse model that faithfully represents the human dementias caused by the mutation in BRI2. In this model APP processing is increased and causes memory loss. Given the fact that these mice reproduce accurately the genetic defects of patients, they are ideal to dissect the pathogenic mechanisms that cause dementia in humans. Therefore, this model is suitable for testing therapies for human dementias, including Alzheimer's disease. The studies proposed in this grant application will also serve as a conceptual foundation to development BRI2-like drugs that reduce APP processing without inhibiting the enzymes that mediate processing of APP. Name of organization or government: Brigham and Women's Hospital (H) Purpose of Grant or Assistance: Alzheimer's Disease Reasearch by Dominic Walsh, PhD Entitled: (A2013059S) Coming to Grips with Brain-Derived Water-Soluble A-Beta. Investigator's Summary: Alzheimer's disease (AD) is a devastating disorder for which there is no cure or effective treatment. A large weight of evidence suggests that a small protein, known as A?, plays a central role in causing AD, however, certain fundamental gaps in our knowledge about A? have been ignored or not rigorously addressed. Given the unsustainable burden that AD is now placing on healthcare systems worldwide and the limited resources that can be directed to research, it is essential that outstanding doubts about the role of A? in AD be directly and swiftly dealt with. In this proposal, we aim to tackle one central issue - the identification from human brain of toxic forms of A? that cause AD. Name of organization or government: Massachusetts General Hospital (H) Purpose of Grant or Assistance: Alzheimer's Disease Reasearch by Se Hoon Choi, PhD Entitled: (A2013140F) ADAM10 Regulates Adult Hippocampal Neurogenesis. Investigator's Summary: Alzheimer's disease (AD) destroys brain cells, causing memory loss and problems with thinking and behavior severe enough to affect work, lifelong hobbies, and social life. New neurons are born in the adult brain (called "adult neurogenesis") and this process is impaired in AD, suggesting that impaired cognitive function in AD might, at least in part, be due to impaired neurogenesis in the adult brain. ADAM10 is a protein that plays an important role in AD, as it prevents the generation of a toxic protein that causes AD. We hypothesize that ADAM10 also plays critical roles in adult neurogenesis, and we propose various animal and cell culture experiments to validate our hypothesis. Name of organization or government: Mayo Clinic Jacksonville (H) Purpose of Grant or Assistance: Alzheimer's Disease Reasearch by Nilufer Ertekin-Taner, MD, PhD Entitled: (A2013157S) Target Pathway Discovery in AD Using Transcriptomics. Investigator's Summary: Genetic studies that survey the complete human genome for variants that associate with Alzheimer's disease (AD) risk, could be key for identifying potential drug targets, though such studies cannot discover the precise mechanism of action of the genetic factors, which is a significant obstacle in the translation of their findings to therapies. Our approach is novel in that we combine information from genetic studies of AD and our large human brain gene expression study to discover genetic factors that increase risk of AD by modifying levels of genes in the brain. In this proposal, we plan to advance our knowledge in this area generated by our strong preliminary data, by uncovering the precise gene expression changes and their biological consequence that lead to AD risk. The results from this proposal will enable downstream innovative drug discovery approaches aimed at rectifying the misregulated brain gene expression that is likely to be an important disease mechanism in AD. Name of organization or government: The Curators of the University of Missouri (H) Purpose of Grant or Assistance: Alzheimer's Disease Reasearch by Laurie Erb, PhD Entitled: (A2013171S) Novel Cerebrovascular Regulation in Alzheimer's Disease. Investigator's Summary: Alzheimer's Disease (AD) and other neurodegenerative diseases are often preceded by malfunctions in the cerebrovascular system, including decreased blood flow in the brain, which leads to hypoxia (low oxygen levels), breakdown of the blood-brain barrier and, ultimately, to brain atrophy and death. It is known that endothelial cells that line blood vessels are important regulators of blood flow and recent work indicates that a nucleotide receptor in endothelial cells (P2Y2R) is activated under hypoxic conditions and causes relaxation of blood vessels and increases blood flow. Our recent work with a mouse model of AD shows that global deletion of the P2Y2R (i.e. removal from all cell types) greatly accelerates neuronal death and the appearance of other classic AD symptoms. Studies in this proposal will investigate whether cerebrovascular changes precede the development of AD symptoms in our AD mouse model and whether the P2Y2R in endothelial cells, in particular, is important for mediating these events. Name of organization or government: Yale University (H) Purpose of Grant or Assistance: Alzheimer's Disease Reasearch by Stephen Strittmatter, MD, PhD Entitled: (A2013184S) Prion Protein Antagonists for Alzheimer's Therapy. Investigator's Summary: In Alzheimer's disease, chemical connections (synapses) between neurons are damaged and cognition is impaired. We have found that amyloid beta binds to Prion protein at synapses to trigger this process. Here, we seek to discover and validate drugs that protect Prion protein from amyloid beta and thereby prevent the initiation of Alzheimer's malfunction. Name of organization or government: Boston University (H) Purpose of Grant or Assistance: Alzheimer's Disease Reasearch by David Harris, MD, PhD Entitled: (A2013245S) Treating Alzheimer's Disease with Prion Protein Ligands. Investigator's Summary: Alzheimer's disease is a devastating disorder of memory that currently afflicts 5 million people in the U.S., and for which there is no effective cure. We have identified a set of novel drugs that bind tightly to a key brain component called the prion protein, thereby possibly blocking its ability to produce toxic effects during Alzheimer's disease. In this project, we will pinpoint how these drugs interact with the prion protein, improve their chemical properties, and test whether they cure Alzheimer's disease in animal models. This work will help establish whether these promising drugs will prove to be effective treatments for Alzheimer's disease in human patients. Name of organization or government: The Cleveland Clinic Foundation (H) Purpose of Grant or Assistance: Alzheimer's Disease Reasearch by Crystal Miller, B.S., PhD Entitled: (A2013252F) The Role of Microglial-Specific MyD88-Dependent Signaling in Tauopathies. Investigator's Summary: In Alzheimer's Disease and other tauopathies, in which tau protein accumulates abnormally in neurons, inflammation is thought to negatively contribue to pathology. Since we know that microglia regulate inflammation, we have developed a model in which we can test the specific contribution of microglia to pathology at different stages of disease. This project seeks to determine whether a particular signaling pathway in microglia is harmful or helpful. The identification of the contribution of this pathway and others will suggest novel therapeutic targets for tauopathies. Name of organization or government: Cedars-Sinai Medical Center (H) Purpose of Grant or Assistance: Alzheimer's Disease Reasearch by Maya Koronyo, PhD Entitled: (A2013328S) Therapeutic Roles of ACE-Overexpressing Monocytes in Alzheimer's Disease. Investigator's Summary: Alzheimer's disease (AD) is the most common cause of senile dementia in the United States, and is the sixth leading cause of death. The aim of this project is to investigate the unique role of a peptidase, angiotensin-converting enzyme (ACE), over-expressed by immune cells, in coping with the neuropathology associated with AD in a murine model. The proposed studies will contribute to the understanding of the roles of peptidases and monocytes in AD pathophysiology and have the potential to open areas for AD treatment or prevention involving immune-based approaches. Results from these studies may positively impact the availability of therapies for AD as well as alleviate some of the socio-economic burden borne by patients and their caregivers. Name of organization or government: Boston University (H) Purpose of Grant or Assistance: Alzheimer's Disease Reasearch by Hirohide Asai, MD, PhD Entitled: (A2013329F) The Cellular Mechanism of Tau Dissemination. Investigator's Summary: This proposal is designed to characterize the molecular mechanism of tau dissemination, which occurs as neurofibrillary tangle formation in the affected brain regions of Alzheimer's disease and frontotemporal dementia. We will determine if this is mediated by neuron-to-neuron or neuron-to-glia transfer of aggregated tau protein, with specific focus on the role of microglia, the brain resident phagocytes, in tau transcytosis in the diseased brain. This study is critically relevant to understand the progression of devastating diseases and will elucidate a potential therapeutic target. Name of organization or government: Washington University (H) Purpose of Grant or Assistance: Alzheimer's Disease Reasearch by Carlos Cruchaga, PhD Entitled: (A2013359S) Identification of Novel CSF Endophenotypes and Genetic Variants for AD by Mendelian Randomization. Investigator's Summary: The identification of the proteins and genes that cause a neurodegenerative disease, such as Alzheimer's disease is the first step to identify potential therapeutic targets and effective treatments. Previous studies have identified clusterin and VILIP1 as risk factor or biomaker for Alzheimer's disease. In this project, we plan to use a very innovative approach, Mendelian randomization, to analyze whether clusterin and VILIP1 are proteins involve in the causative pathway of Alzheimer's Disease. The we will perform genetic studies using the protein levels of these proteins and APOE and FABP, which we know are in the causative pathway of Alzheimer's Disease, as quantitative traits. By doing this, we expect to identify additional variants and genes associated with Alzheimer's disease. This new approach is expected to contribute to the identification of novel therapeutic targets. Name of organization or government: Michigan State University (H) Purpose of Grant or Assistance: Alzheimer's Disease Reasearch by Lester Binder, PhD Entitled: (A2013364S) Tau Oligomers and Their Potential Role in Toxicity Leading to Alzheimer's Disease. Investigator's Summary: Tau is one of the main proteins that is responsible for causing Alzheimer's Disease (AD). Tau can have many different structures and we would like to identify the structure that leads to AD. If we are successful in doing so, we believe we can then target these particular structures for therapy. Name of organization or government: Baylor College of Medicine (H) Purpose of Grant or Assistance: Alzheimer's Disease Reasearch by Hongmei Li, PhD Entitled: (A2013370F) Understanding the Role of Cerebral Vasculature AD Pathology Using a Knock-in Mouse Model with CAA. Investigator's Summary: We will study how the reduction of brain blood flow during aging contributes to the increasing risk of getting Alzheimer's disease. We aim to evaluate a series of molecules that might be responsible for event, and explore a promising new nano-drug to be used to prevent and treat the disease. Name of organization or government: University of California, Davis (H) Purpose of Grant or Assistance: Alzheimer's Disease Reasearch by Lee-Way Jin, MD, PhD Entitled: (A2013414S) KCa3.1 Blockers for Alzheimer's Disease Therapy. Investigator's Summary: We propose to identify compounds that inhibit a potassium channel in the brain called KCa3.1. This channel plays an important role in brain inflammation that promotes the progression of Alzheimer's disease. Ths approach has been shown to be safe, but all the existing KCa3.1 blockers are not suitable for treating brain diseases and cannot be taken orally. We will improve the drug properties of these KCa3.1 blockers to make them suitable for treating Alzheimer's disease. Name of organization or government: Massachusetts General Hospital (H) Purpose of Grant or Assistance: Alzheimer's Disease Reasearch by Vivek Gautam, PhD Entitled: (A2013478F) Role of Neurexins in Alzheimer's Disease. Investigator's Summary: This research proposal will provide novel insights into the pathology of Alzheimer's disease. Name of organization or government: University of Florida (H) Purpose of Grant or Assistance: Alzheimer's Disease Reasearch by Paramita Chakrabarty, PhD Entitled: (A2013504S) Innate Immune System and Tauopathy. Investigator's Summary: One of the most important factors that underlie degeneration of neurons in an Alzheimer's disease patient brain is massive inflammation. Inflammation is a natural reaction of the body to toxins, bacteria and foreign particles. Cytokines are the messengers during inflammation and carry information between different cells. In the first part of the grant, using novel molecular biology techniques, we will try to understand whether cytokines and other related proteins levels change with the progressive appearance and development of brain pathology in Alzheimer disease mouse models. Further, using different classes of cytokines in the brains of these mice, we will explore whether one class of cytokine ('inflammatory') drive the disease and kill neurons in the process whereas the opposing kind ('anti-inflammatory' cytokines) ameliorate the disease and are protective. Name of organization or government: The University of Texas Southwestern Medical Center at Dallas (H) Purpose of Grant or Assistance: Alzheimer's Disease Reasearch by Joachim Herz, MD Entitled: (A2013524S) Reversing the APOE4 Risk for Alzheimer's Disease. Investigator's Summary: ApoE4 is the most important risk factor for Alzheimer's disease. In previous work funded by BrightFocus we uncovered a molecular mechanism by which ApoE4 likely manifests the disease risk, by causing a traffic jam inside the nerve cells. We have now recently discovered a conceptually innovative way to prevent this traffic jam using small molecules. In this application we propose to develop this new discovery toward a preventive treatment for Alzheimers disease. Name of organization or government: Mayo Clinic Jacksonville (H) Purpose of Grant or Assistance: Alzheimer's Disease Reasearch by Leonard Petrucelli, PhD Entitled: (A2013546S) HDAC6 and Tau Pathobiology. Investigator's Summary: Alzheimer's disease is caused by the abnormal buildup of tau, a protein within brain cells that, when toxic, disrupts the ability of cells to communicate with each other, which leads to memory loss and other symptoms associated with the disease. We recently found that decreasing the function of an enzyme known as HDAC6 effectively decreases the amount of tau protein in cells. In this project, we will test our theory that mice treated with drugs to reduce HDAC6 activity will show lower levels of tau protein in the brain. If successful, this work could lead to the development of a new treatment for Alzheimer's disease that takes aim at tau buildup. Name of organization or government: Columbia University Medical Center (H) Purpose of Grant or Assistance: Alzheimer's Disease Reasearch by Ismael Santa-Maria Perez, PhD Entitled: (A2013555F) Role of Micro-RNAs in Tangle Predominant Alzheimer's Disease. Investigator's Summary: Neurofibrillary tangles (NFT), caused by clumping of toxic tau protein in the brain, are hallmarks of Alzheimer's disease (AD). The lack of a defined mechanism of NFT formation is impeding the development of new therapies. Dr. Santa-Maria Perez and colleagues will determine what is causing tau accumulation by looking for disease-causing variations in genes associated with AD, and by deciphering whether small gene "silencers," called microRNAs, are the culprits for making one AD gene, called microtubule-associated protein tau (MAPT), go toxic. This research may reveal new targets of this type of Alzheimer's disease suitable for therapy. Name of organization or government: Massachusetts General Hospital (H) Purpose of Grant or Assistance: Alzheimer's Disease Reasearch by Bradley Hyman, MD, PhD Entitled: (A2013 21st CBT) Evaluate Mobile Computing Devices in a Well Characterized Longitudinal Clinical Research Population. Name of organization or government: Alzheimer's Drug Discovery Foundation (H) Purpose of Grant or Assistance: Alzheimer's Disease Reasearch Entitled: (C2013999) A Randomized Controlled Study to Evaluate the Effect of Bexarotene, an RXR Agonist, on BetaAmyloid. Name of organization or government: Northwestern University (H) Purpose of Grant or Assistance: National Glaucoma Research by Matthew Glucksberg, PhD Entitled: (G2013044) Effect of Rapid Depressurization on Cultured Cells. Investigator's Summary: The importance of controlling pressure in the eye is known to be a factor in the damage to vision caused by glaucoma. The reason why this is so is still not known, but there are several hypotheses involving the stresses and strains caused by elevated pressure in the tissue of the optic nerve. However, in recent years an alternate hypothesis has been presented that it is not the stresses and strains (or not the stresses and strains alone) caused by the high pressure, but the high pressure itself that does the damage, and this has been supported by some studies. Here we put forward an additional idea that may explain the results of the direct-pressure hypothesis, and that is that rapid relief of the applied hydrostatic pressure causes a rapid decompression related to ultra-transient microbubble formation that affects cell function. Name of organization or government: Temple University (H) Purpose of Grant or Assistance: National Glaucoma Research by Yang Hu, MD, PhD Entitled: (G2013046) Neuroprotection by Inhibition of ER Stress in Glaucoma. Investigator's Summary: Loss of retinal ganglion cells and their axons due to optic nerve injury account for visual function deficits in glaucoma. We hypothesize that the underlying mechanisms involves optic nerve injury-induced ER stress. We propose to manipulate ER stress molecules to promote neuroprotection and therefore to preserve vision function of glaucoma patients. Name of organization or government: Board of Regents of the University of Wisconsin System (H) Purpose of Grant or Assistance: National Glaucoma Research by Curtis Brandt, PhD Entitled: (G2013050) Enhancement of Gene Expression for Glaucoma Therapy. Investigator's Summary: Gene therapy to lower intraocular pressure is an approach for long-term glaucoma therapy that has the advantage of reducing the number of therapeutic treatments and thereby assuring patient compliance. We wish to use viral vectors (a virus capable of carrying/transporting genes) to deliver these genes to the front part of the eye where intraocular pressure is regulated. However, there are factors that limit the ability to produce the desired effect and reproducibility of the delivery, and ultimately the expression of the desired gene. We will use several approaches to overcome these limitations in order to advance the development of glaucoma gene therapy. Name of organization or government: Johns Hopkins University (H) Purpose of Grant or Assistance: National Glaucoma Research by Zhenhua Xu, PhD Entitled: (G2013058) Role of Nrf2 in Protecting RGC in Glaucoma. Investigator's Summary: Oxidative stress and inflammatory processes are thought to play important roles in the pathogenesis of glaucoma. The research proposed in this application will determine the role Nrf2 (NF-E2-related factor 2), a critical cellular stress-responsive molecule, in preventing ganglion cell death. We will also evaluate the potential of Nrf2 activation drugs in preventing cell death and vision loss in the rodent model of glaucoma. Name of organization or government: University of Pittsburgh (H) Purpose of Grant or Assistance: National Glaucoma Research by Kevin Chan, PhD Entitled: (G2013077) Effects of Ocular Hypertension on Visual Brain Damage. Investigator's Summary: Glaucoma is the second leading cause of blindness in the world. Although elevated eye pressure is a major risk factor, recent evidence suggested the involvement of the visual brain, apart from the eye, in the early degenerative mechanisms of glaucoma. Our goal of this project is to develop novel structural, metabolic and functional magnetic resonance imaging techniques for global, non-invasive and longitudinal measurements of the glaucomatous damage, disease progression and neuroprotection along the visual pathway under 3 different levels of chronic ocular hypertension with or without timolol treatment. The development of novel methods for characterizing chronic glaucoma and neuroprotection in the visual system can potentially lead to more timely intervention and targeted treatments in reducing the burden of this disease. Name of organization or government: Regents of the University of Michigan (H) Purpose of Grant or Assistance: National Glaucoma Research by Philip Gage, PhD Entitled: (G2013084) A New, Inducible, and Rapid Model of Glaucoma in Mice. Investigator's Summary: Mouse models provide an important way to study how mutations in a gene cause disease, and to develop new potential therapies to treat the disease. We have made mice that contain a genetic "switch" that lets us turn off a glaucoma gene (Pitx2) in mature mice. These mice appear to provide a model for studying glaucoma that is both inducible and develops rapidly, meaning that we and others should be able to make exciting discoveries more rapidly and at a much cheaper cost. What we plan to do in these experiments is to look much more carefully at these mice than we have previously in order to more completely understand how they work. Name of organization or government: University of Oklahoma Health Sciences Center (H) Purpose of Grant or Assistance: National Glaucoma Research by Michael Elliott, PhD Entitled: (G2013092) Caveolins as Novel Mechanosensors in Aqueous Outflow. Investigator's Summary: Elevated eye pressure is a major risk factor for glaucoma and this pressure is regulated by controlling the drainage of fluid from the eye. There are currently no glaucoma medications that target the major pathway of fluid drainage in the eye yet this pathway is the source of the primary pathology in glaucoma. This project is designed to test a novel mechanism by which the eye regulates fluid drainage and how this mechanism might be dysfunction in glaucoma. Name of organization or government: University of Iowa (H) Purpose of Grant or Assistance: National Glaucoma Research by John Fingert, MD, PhD Entitled: (G2013103) Stem Cell Approaches to Glaucoma. Investigator's Summary: Retinal ganglion cells are the part of the eye that are primarily affected by glaucoma, however, these cells are very difficult to study in the laboratory. Consequently, we have used a stem cell-based approach to generate retinal ganglion cells in culture. We will use these cells to study the mechanism by which a known glaucoma gene, TANK binding kinase 1 (TBK1), leads to retinal ganglion cell loss and eye disease. These studies will provide new insights in the biology of glaucoma and will facilitate the development of new glaucoma therapies. Name of organization or government: University of Miami, Miller School of Medicine (H) Purpose of Grant or Assistance: National Glaucoma Research by Kenneth Muller, PhD Entitled: (G2013107) Cell Therapy for Retinal Ganglion Cell Loss in Glaucoma. Investigator's Summary: Glaucoma causes blindness by destroying retinal ganglion cells, the output nerve cells of the retina, which are not replaced. Our proposed project will transplant retinal ganglion cells into retinas in a mouse model of glaucoma so that the replacement cells become wired into the retina and recover an electrical response to light. In some cases the replacements will be cultured to form retinal ganglion cells before transplantation, since retinal ganglion cell replacements may otherwise be difficult to obtain. There is reason to believe that in the future the transplanted cells will be able to grow to restore vision. Name of organization or government: University of Illinois Medical Center (H) Purpose of Grant or Assistance: National Glaucoma Research by Beatrice Yue, PhD Entitled: (G2013110) Fibril/Oligomer Formation by Optineurin In Vitro. Investigator's Summary: Protein aggregation into multimers or the so-called amyloid fibers is a hallmark in neurodegenerative disorders such as Alzheimer's. As glaucoma is considered to be an "ocular Alzheimer's disease", we are interested in learning whether optineurin, a product of glaucoma disease gene, is similarly capable of forming the aggregates and causing problems, especially with optineurin mutations. If so, we will find a way to minimize or prevent the aggregation to eventually develop therapies clinically. Name of organization or government: University of Miami-Bascom Palmer Eye Institute (H) Purpose of Grant or Assistance: National Glaucoma Research by Richard Lee, MD, PhD Entitled: (G2013121) Optogenetic Stimulation for Axonal Regeneration. Investigator's Summary: Glaucoma is an eye disease that is associated with damage to retinal ganglion and the connections of these cells to the brain that allow for vision. Using a method to specifically stimulate damaged retinal ganglion cells, we have forced these cells to regrow new connections toward the brain after damage. Our goal is use this new method of stimulation to prevent retinal ganglion cells from losing these brain connections by allowing them to maintain these brain connections to preserve vision. Name of organization or government: Weill Medical College of Cornell University (H) Purpose of Grant or Assistance: National Glaucoma Research by Anna Demetriades, MD, PhD Entitled: (G2013141) Neurotrophic Biofactories for the Treatment of Glaucoma. Investigator's Summary: Glaucoma is the result of retinal ganglion cell (RGC) death in the eye which ultimately leads to vision loss in patients. The aim of this study is to develop a novel treatment for our patients by identifying a new way to slow down and prevent RGC death. We will use gene therapy to deliver neuroprotective proteins to specific cells within the retina and determine whether it is best to deliver these proteins directly to RGCs or to adjacent cells in order to optimally improve their survival. Name of organization or government: Hunter College, CUNY (H) Purpose of Grant or Assistance: National Glaucoma Research by Hyungsik Lim, PhD Entitled: (G2013143) Investigating Early Pathogenic Events of Glaucoma by Second-Harmonic Generation. Investigator's Summary: The ability to detect glaucoma as early as possible is important for treating the disease in a timely manner. We have recently found a new way of imaging the retinal nerves, whose aspects are particularly useful for identifying the subtle changes associated with glaucoma. This project will used our newly developed technique to understand how glaucoma occurs. Name of organization or government: Tulane University (H) Purpose of Grant or Assistance: Macular Degeneration Research by Shusheng Wang, PhD Entitled: (M2013007) MicroRNAs in Age-related Macular Degeneration. Investigator's Summary: The goal of the project is to develop a novel therapy that can overcome the problems associated with the current anti-VEGF therapy for wet Age-related macular degeneration (AMD), a leading cause of blindness in the elderly. We propose that tiny pieces of genetic material called microRNAs could have a big role in AMD disease development and therapeutics. The advantage of microRNAs (miR-24 in this proposal) is that they can regulate multiple components of signaling pathways that are critical in AMD pathogenesis in cells. Therefore these tiny microRNAs can potentially be used to treat complex diseases as AMD without performing tedious small molecule drug screening. Name of organization or government: Children's Hospital Boston, Harvard Medical School (H) Purpose of Grant or Assistance: Macular Degeneration Research by Jing Chen, PhD Entitled: (M2013041) Control of Neovascular Age-Related Macular Degeneration by Nuclear Receptor RORalpha. Investigator's Summary: A major cause of blindness in AMD is abnormal blood vessel growth in the back of the eye (choroidal neovascularization), the "wet" form of AMD. The proposed work will help define a novel pathway linking dysregulation of lipid homeostasis with altered inflammatory responses in AMD. Both processes are fundamentally important to the pathophysiology of wet AMD. If successful, this application will identify a new therapeutic approach to treat AMD with specific modulation of a lipid sensing nuclear receptor that modifies inflammation. Name of organization or government: University of California, Riverside (H) Purpose of Grant or Assistance: Macular Degeneration Research by Dimitrios Morikis, PhD Entitled: (M2013106) Drug Discovery for Macular Disease. Investigator's Summary: This research focuses on the discovery of potential therapeutics for age-related macular degeneration (AMD), by targeting the complement system, a part of the immune system implicated in AMD pathogenesis. The project involves synergy between computational screening of chemical compounds and experimental testing using a human retinal cell-based model. Name of organization or government: University of Pennsylvania School of Medicine (H) Purpose of Grant or Assistance: Macular Degeneration Research by Venkata Chavali, PhD Entitled: (M2013122) Association And Functional Characterization Of Long Non-Coding RNAs (lncRNAs) In Age-related Macular Degeneration. Investigator's Summary: The function of long non-coding RNA (lncRNA) in the genome and their role in biological processes and disease is not well studied even though some lncRNA are known to be associated with neurological diseases. We propose to sequence the total retina and retinal pigment epithelium (RPE) tissue transcriptome from normal and age-related macular degeneration (AMD) donor eyes and reveal the differentially expressed (DE) lncRNAs and messenger RNAs (mRNAs) in the retinal and RPE/choroid tissues relevant to AMD. We intend to elucidate and characterize the role of DE lncRNAs in AMD and understand how lncRNAs potentially influence the development of AMD. The outcome of our project will provide novel molecular tools and pathways to understand AMD pathobiology, which are not explored to date. Elucidation of the expression changes in AMD may lead to development of new biomarkers and therapy targeted at altering expression. Name of organization or government: Harvard Medical School (H) Purpose of Grant or Assistance: Macular Degeneration Research by Chenghua Gu, DVM, PhD Entitled: (M2013127) The Role of Semaphorin 3E Signaling in Neovascular Age-Related Macular Degeneration. Investigator's Summary: Patients with neovascular age-related macular degeneration (NVAMD) have benefited from therapies that inhibit the formation of new blood vessels in the retina. These medications on the market, including pegaptanib (Macugen), ranibizumab (Lucentis) and bevacizumab (Avastin), directly bind VEGF, a molecule that stimulates blood vessel formation in the eye. We propose to improve the therapies for neovascular AMD by finding novel therapies that could be used alone or in combination with the existing therapeutics. Our laboratory has recently identified a new signaling pathway through Semaphorin 3E and Plexin-D1 that inhibits the function of VEGF. More importantly, this pathway only functions in the newlyformed abnormal blood vessels, but not in the normal vasculature. Thus, through searching for new peptides and drugs that target this pathway, we will discover novel therapeutic agents that expand our repertoire in fighting AMD and improve the quality of life for patients suffering from AMD. Name of organization or government: University of Oklahoma Health Sciences Center (H) Purpose of Grant or Assistance: Macular Degeneration Research by Martin-Paul Agbaga, PhD Entitled: (M2013130) What Triggers Mutant ELOVL4 Induced Blindness in STGD3? Investigator's Summary: Both Age Related Macular Degeneration (AMD) and juvenile autosomal dominant Stargardt macular dystrophy (STGD3) share similar clinical features that result in irreversible blindness. The only difference is that, while AMD blindness starts in people over 60 years of age, STGD3 blindness starts in their teenage years. We reasoned that since AMD and STGD3 share similar clinical features, there must be a common mechanism that contributes to the death of photoreceptor cells leading to blindness in both type of patients and that identification of the this mechanism will help us to develop better drugs for treating this patients. The long-term goal of my studies is to use animal models of STGD3 to hunt and identify what set off the death of the photoreceptor cells in these patients with the goal that once we find the culprit, we can design effective drugs to silence it and preserve vision in STGD3 and some AMD patients. Name of organization or government: Weill Medical College of Cornell University (H) Purpose of Grant or Assistance: Macular Degeneration Research by Marcelo Nociari, PhD Entitled: (M2013146) Removal of Lipofuscin Bisretinoids from RPE by Beta-cyclodextrins. Investigator's Summary: With age, our eyes accumulate waste in retinal pigment epithelium (RPE), which support the life and function of photoreceptors (light sensitive cells in the eye); in advanced stages, RPE and photoreceptors die. In some genetic forms of blindness, this waste accumulates much faster in RPE resulting in blindness by age 30. We have discovered drugs that remove this waste from RPE. The proposed experiments will develop strategies to make waste removal more efficient. We expect that this will result in useful drugs to treat human blinding diseases, including Age Related Macular Degeneration. Name of organization or government: University of California, San Diego (H) Purpose of Grant or Assistance: Macular Degeneration Research by Jonathan Lin, MD, PhD Entitled: (M2013158) Retinal Pigment Epithelium Stem Cells for Age-Related Macular Degeneration Treatment. Investigator's Summary: Loss of retinal pigment epithelial (RPE) cells is a key pathologic feature of age-related macular degeneration (AMD). Human stem cells can be differentiated into functional RPE and show great promise as a new regenerative medicine therapy to prevent vision loss in people with AMD. Our proposed research will develop a new source of stem cells endogenously present within the human eye to develop new sources of RPE for clinical use in patients with AMD. Name of organization or government: The Schepens Eye Research Institute (H) Purpose of Grant or Assistance: Macular Degeneration Research by Magali Saint-Geniez, PhD Entitled: (M2013161) Role of PGC-1 Isoforms in RPE Function and Oxidative Stress: Implications for Age-Related Macular Degeneration. Investigator's Summary: The goal of this study is to test the hypothesis that new critical regulators of cells metabolism and survival, called PGC-1, may play an essential role in the function of RPE cells and that they protect RPE cells from oxidative damage and degeneration. RPE, a pigmented cell layer at the back of the eye, supports photoreceptor function and has been implicated in age-dependent macular degeneration (AMD),a leading cause of blindess. Insights into the ability of PGC-1 to regulate function and survival in RPE may thus provide a new target for therapeutics to prevent retinal degenerative disorders such as AMD. National Development LLC 22512 Gateway Center Drive Clarksburg MD 20871 237337229 Property rental and management MD 554039 4746277 N/A American Health Assistance LLC 22512 Gateway Center Drive Clarksburg MD 20871 237337229 Owner of BrightFocus headquarters MD 0 4263202 N/A 1