FRIEDREICH'S ATAXIA RESEARCH ALLIANCE

RESEARCH AND GRANT PROGRAM FARA DEPLOYS FINANCIAL RESOURCES TO ACCELERATE RESEARCH FOR FRIEDREICH'S ATAXIA (FA). IN 2023, FARA AWARDED $9 MILLION IN RESEARCH FUNDING. THIS INCLUDED 37 GRANT PROJECTS THROUGH FARA'S INVESTIGATOR-INITIATED GRANT PROGRAM, INSTITUTIONAL BASED RESEARCH, AND FARA DIRECTED PROJECTS. IT ALSO INCLUDED FUNDING A PATIENT REGISTRY AND LONGITUDINAL NATURAL HISTORY THROUGH THE FA GLOBAL CLINICAL CONSORTIUM WHICH IS DESCRIBED IN THE SECOND PROGRAM SECTION BELOW. FARA GRANT PROGRAM FARA'S INVESTIGATOR-INITIATED GRANT PROGRAM AWARDED TWENTY-TWO NEW GRANTS AND APPROVED CONTINUED FUNDING FOR FIFTEEN GRANTS. RESEARCHERS IN TEN COUNTRIES ARE RECEIVING RESEARCH FUNDING FROM FARA. THE PROGRAM IS A COMPETITIVE FUNDING MECHANISM THAT SUPPORTS RESEARCH TO FURTHER THE UNDERSTANDING OF FA AND PROMOTE THERAPEUTIC DISCOVERY AND DEVELOPMENT. FARA PRIORITIZES FUNDING PROJECTS THAT FILL GAPS IN KNOWLEDGE OF DISEASE MECHANISMS, SUPPORT EARLY DEVELOPMENT OF THERAPEUTIC INTERVENTIONS, ESTABLISH AND ADVANCE THE DEVELOPMENT OF TOOLS FOR DRUG DEVELOPERS AND ACADEMIC RESEARCHERS, AND FOCUS ON CLINICAL RESEARCH AND TRIALS. SEVERAL OF THESE GRANTS WERE CO-FUNDED WITH FARA'S FA ADVOCACY GROUP PARTNERS; THIS COLLABORATIVE APPROACH BOTH INCREASES THE NUMBER OF AVAILABLE RESEARCH DOLLARS AND HELPS TO MINIMIZE DUPLICATION OF EFFORT. WITH FARA'S GOAL IN MIND OF INSPIRING AND SUPPORTING JUNIOR INVESTIGATORS AND BUILD THE NEXT GENERATIONS OF FA SCIENTISTS, IN 2023, FARA ESTABLISHED TWO NEW PROGRAMS: THE FARA GRADUATE RESEARCH FELLOWSHIP TO SUPPORT YOUNG RESEARCHER ENGAGED IN GRADUATE STUDY LEADING TO A PH.D. DEGREE AND THE FARA FELLOW PROGRAM THAT PROVIDES MENTORSHIP, TRAINING AND NETWORKING OPPORTUNITIES TO TALENTED YOUNG SCIENTISTS. THE FARA FELLOWS PROGRAM WAS INITIATED WITH SUPPORT FOR FOUR FELLOWS FROM STANFORD UNIVERSITY, COLUMBIA UNIVERSITY, CALTECH, AND UT SOUTHWESTERN. FARA HAS ALSO IDENTIFIED OPPORTUNITIES TO FUND RESEARCH AT INSTITUTIONS WHERE THERE ARE MULTIPLE INVESTIGATORS WITH AN EXPERTISE AND COMMITMENT TO FA RESEARCH AND/OR OPPORTUNITY TO LEVERAGE TECHNOLOGIES, INNOVATION OR NEW GROWTH TO THE FA COMMUNITY. BY ESTABLISHING THESE INSTITUTIONAL FUNDING PROGRAMS, FARA IS ABLE TO PROMOTE COLLABORATION AND SYNERGY ACROSS BASIC, TRANSLATIONAL AND CLINICAL RESEARCH, PROVIDE A LONGER-TERM COMMITMENT FOR RESEARCH, ATTRACT NEW INVESTIGATORS, AND LEVERAGE THE INSTITUTIONS RESOURCES AND ENGAGEMENT. FARA PROVIDES INSTITUTIONAL BASED RESEARCH SUPPORT FOR THE FA CENTER OF EXCELLENCE AT PENN MEDICINE/CHILDREN'S HOSPITAL OF PHILADELPHIA AND THE FA ACCELERATOR PROGRAM AT THE BROAD INSTITUTE. FRIEDREICH'S ATAXIA CENTER OF EXCELLENCE, PHILADELPHIA, PA THE FA CENTER OF EXCELLENCE (COE) IS A TRANSLATIONAL RESEARCH AND CLINICAL CARE CENTER DEVOTED TO FRIEDREICH ATAXIA: EXPEDITING BASIC SCIENCE AND DRUG DISCOVERY FINDINGS TO NEW TREATMENTS AND DEDICATING RESOURCES TO CLINICAL RESEARCH AND CARE TO FURTHER UNDERSTAND THE DISEASE, INFORM DRUG DEVELOPMENT AND IMPROVE OUTCOMES FOR INDIVIDUALS LIVING WITH FA. THE CENTER WAS ESTABLISHED IN MARCH 2014, WITH A COMMITMENT TO PENN MEDICINE/ CHILDREN'S HOSPITAL OF PHILADELPHIA, PRESENTED BY FARA IN PARTNERSHIP WITH THE HAMILTON AND FINNERAN FAMILIES/ CUREFA FOUNDATION. PROJECTS AND INVESTIGATORS WITH CONTINUED FUNDING INCLUDED DR. ROB WILSON- DRUG DISCOVERY, DR. DAVID LYNCH- TRANSLATIONAL AND CLINICAL NEUROSCIENCE RESEARCH, DR. IAN BLAIR- BIOMARKER DISCOVERY, DR. KIM LIN- CARDIAC RESEARCH, DR. SHANA MCCORMACK- METABOLISM AND ENDOCRINOLOGY, AND DR. CLEMINTINA MASAROS- LIPID AND METABOLIC PROFILING. THE COE ESTABLISHED RESEARCH INFRASTRUCTURE CONSISTING OF FOUR CORE AREAS- NEUROLOGY, CARDIAC, BIOMARKER AND DRUG DISCOVERY. THE CENTER NOT ONLY SUPPORTS WORK WITHIN THESE DISCIPLINES, BUT ALSO FOSTERS EFFICIENT COLLABORATION AND SYNERGY ACROSS THEM. OVER THE PAST YEAR, THIS SYNERGY HAS RESULTED IN MEANINGFUL STRIDES FORWARD IN FA RESEARCH. FOR EXAMPLE, THE BASIC RESEARCH PROGRAMS HAVE PROVIDED INSIGHTS INTO CHANGES IN THE CEREBELLUM THAT SUGGEST A NOVEL THERAPEUTIC TARGET, A SPECIFIC TYPE OF GLUTAMATE RECEPTOR. WORK IN MODEL SYSTEMS HAS ALSO SUGGESTED THAT THE IMMUNE SYSTEM MAY PLAY A ROLE IN FA, PROVIDING AN ADDITIONAL AVENUE FOR THERAPEUTIC INTERVENTION. THE LABS AT CHOP HAVE DEVELOPED SENSITIVE AND SPECIFIC ASSAYS FOR FORMS OF FRATAXIN, AS WELL AS ASSAYS FOR METABOLITES THAT ARE ALTERED IN FA. THESE BIOMARKER ASSAYS ARE CRITICAL TO THERAPEUTIC DEVELOPMENT. FINALLY, THE CLINICIANS AT CHOP HAVE MADE MAJOR CONTRIBUTIONS TO THE CLINICAL CARE GUIDELINES FOR THE TREATMENT AND MANAGEMENT OF FA AND HAVE PARTICIPATED IN THE TESTING OF THERAPEUTICS IN CLINICAL TRIALS. AT THE END OF 2023, FOUR COE INVESTIGATORS WERE AWARDED APPROXIMATELY $7M IN EXTERNALLY-FUNDED GRANTS FROM THE DEPARTMENT OF DEFENSE'S CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS (CDMRP). THIS IS A GREAT EXAMPLE OF HOW THE FOUNDATIONAL WORK SUPPORTED BY FARA ATTRACTS SIGNIFICANT ADDITIONAL FUNDING TO CONTINUE TO ADVANCE THESE IMPORTANT FA PROGRAMS. FRIEDREICH'S ATAXIA ACCELERATOR AT THE BROAD INSTITUTE OF MIT AND HARVARD THE FRIEDREICH'S ATAXIA ACCELERATOR (FAA) AT THE BROAD INSTITUTE OF MIT AND HARVARD WAS ESTABLISHED IN AUGUST 2020. FUNDED BY FARA, IN COLLABORATION WITH THE CUREFA FOUNDATION AND ENDFA, THE FAA IS A COLLABORATIVE, MULTI-DISCIPLINARY EFFORT AIMED AT GALVANIZING RESEARCH INTO FA AND SEEDING A GROWING COMMUNITY ACROSS BROAD, MIT, HARVARD AND AFFILIATED INSTITUTIONS COMMITTED TO TACKLING FA. IT IS LED BY VAMSI MOOTHA, MD, THE FAA INVESTIGATORS INCLUDE GARY RUVKIN, PHD, DAVID LIU, PHD, CHRISTINE SEIDMAN, MD, JONATHAN SEIDMAN, PHD, ANOOPUM GUPTA, MD AND ANTHONY PHILIPPAKIS, MD. THE WORK AT THE FAA HAS YIELDED INSIGHTS IN KEY RESEARCH AREAS FOR FA IN 2023. THE MOOTHA LAB HAS ADVANCED AN UNDERSTANDING OF THE INTERACTION OF FRATAXIN FUNCTION AND ENVIRONMENTAL STRESSORS, WHILE THE RUVKUN LAB HAS GENERATED PRELIMINARY DATA ON POTENTIAL MECHANISMS TO BYPASS FRATAXIN LOSS. THE LIU LAB, EXPERTS IN GENE EDITING APPROACHES, ARE OPTIMIZING THIS TECHNIQUE FOR REACTIVATING FRATAXIN EXPRESSION. FINALLY, THE SEIDMANS HAVE BROUGHT DEEP EXPERIENCE AND KNOWLEDGE OF CARDIOMYOPATHY AND HOW FA IS SIMILAR TO OTHER DISEASES AFFECTING THE HEART POTENTIALLY PROVIDING THE BASIS FOR THE USE OF EXISTING HEART MEDICATIONS FOR FA. FARA DIRECTED RESEARCH IN 2023, FARA FUNDED DIRECTED RESEARCH PROGRAMS INCLUDING: 1. MAINTAINING A REPOSITORY OF FA CELL LINES FOR RESEARCH HTTPS://LABS.UTSOUTHWESTERN.EDU/NAPIERALA-LAB 2. TRACK-FA, A GLOBAL NEUROIMAGING CONSORTIUM ESTABLISHED IN 2020, A NATURAL HISTORY STUDY DESIGNED TO TRACK THE CHANGES IN THE BRAIN AND THE SPINAL CORD IN FA. PARTICIPATING CLINICAL SITES IN USA, BRAZIL, CANADA, GERMANY, AND AUSTRALIA COMPLETED ENROLLMENT IN 2023. THE STUDY ENROLLED 182 INDIVIDUALS WITH FA AND 97 MATCHED CONTROLS AND CONDUCTED NEUROIMAGING OF THE BRAIN AND SPINAL, ALONG WITH CLINICAL OUTCOMES AND BLOOD BIOMARKERS. DATA COLLECTION COMPLETION FOR THE STUDY IS ANTICIPATED BEFORE THE END OF 2025. 3. FOSTERING A COLLABORATIVE EFFORT BETWEEN RESEARCHERS AT UNIVERSITY OF OKLAHOMA, UNIVERSITY OF TEXAS SOUTHWESTERN, AND UNIVERSITY OF PENNSYLVANIA TO STUDY THE PRECISE MECHANISM OF THIS GENE SILENCING IN DIFFERENT TISSUES AND MODELS OVER TIME. 4. DEVELOPMENT AND VALIDATION OF A POTENCY ASSAY FOR USE IN THE DEVELOPMENT OF GENE AND PROTEIN REPLACEMENT THERAPIES. 5. THE AUSTRALIAN GENE AND CELL THERAPY CONSORTIUM 6. LEADING WORK TO CREATE A NEW DISEASE MODEL FOR PRE-CLINICAL RESEARCH, AN FA RAT MODEL. 7. IDENTIFYING AND FUNDING RESEARCH TO UNDERSTAND THE THERAPEUTIC WINDOW (MINIMAL AMOUNT OF FRATAXIN NEEDED FOR A THERAPEUTIC BENEFIT AND THRESHOLD FOR MAXIMUM AMOUNTS OR TOXIC AMOUNTS OF FRATAXIN IN THE CELL. 8. ONGOING MAINTENANCE OF CLINICAL MANAGEMENT GUIDELINES IN FA FOR REFERENCE USE BY PHYSICIANS AND PATIENTS (PUBLISHED IN 2022): FRDAGUIDELINES.ORG 9. RETROSPECTIVE CARDIAC NATURAL HISTORY STUDY-THIS PROJECT WILL RE-ANALYZE EXISTING ECHOCARDIOGRAMS TO QUICKLY ASSESS THE VALUE OF THESE DATA IN UNDERSTANDING AND PREDICTING THE PROGRESSION OF HEART DISEASE IN FA. OF NOTE, FA SHARES SIMILAR SYMPTOMS AND DISEASE MECHANISMS WITH OTHER DISEASES, BOTH RARE AND COMMON. RESEARCH INTO FA CAN PROVIDE INSIGHTS AND ADVANCES IN OTHER DISEASES SUCH AS MITOCHONDRIAL DISEASES, MUSCULAR DYSTROPHIES, DIABETES, AND CARDIOMYOPATHY. A COMPLETE LIST OF 2023 FARA FUNDED GRANTS AND PUBLICATIONS CAN BE FOUND AT: CUREFA.ORG

CLINICAL RESEARCH INFRASTRUCTUREIN ADDITION TO RESEARCH GRANTS, FARA FUNDS THE ONGOING DEVELOPMENT OF DOMAIN RESOURCES IN THE FORM OF VITAL CLINICAL RESEARCH INFRASTRUCTURE. CLINICAL RESEARCH INFRASTRUCTURE REFERS TO THE RESOURCES NEEDED TO FACILITATE ANY TYPE OF RESEARCH, INCLUDING CLINICAL TRIALS THAT INVOLVE PATIENTS. THESE RESOURCES INCLUDE PROGRAMS LIKE: FRIEDREICH'S ATAXIA GLOBAL PATIENT REGISTRY: THE FRIEDREICH'S ATAXIA GLOBAL PATIENT REGISTRY (FAGPR) IS THE ONLY WORLDWIDE REGISTRY OF FRIEDREICH'S ATAXIA PATIENTS. THE GOALS OF THE FAGPR ARE TO COLLECT INFORMATION ON ALL FA PATIENTS IN ONE REGISTRY, TO DEVELOP THE REGISTRY INTO A POWERFUL RESOURCE FOR RESEARCH, AND TO ENGAGE THE FA COMMUNITY IN STUDIES AIMED AT ADVANCING OUR KNOWLEDGE OF FA AND THE TREATMENTS BEING DEVELOPED. FARA PARTNERS WITH INTERNATIONAL PATIENT ADVOCACY ORGANIZATIONS THROUGH A GOVERNANCE BOARD TO ENSURE MULTI-STAKEHOLDER ENGAGEMENT AND OVERSIGHT OF THE FAGPR. MORE THAN 1000 INDIVIDUALS WITH FA ARE ENROLLED AND FAGPR WAS USED TO RECRUIT FOR SEVERAL CLINICAL TRIALS AND MANY CLINICAL RESEARCH STUDIES. TO LEARN MORE, VISIT CUREFA.NET/REGISTRY. FA GLOBAL CLINICAL CONSORTIUM: FARA AND THE FA COMMUNITY'S DEDICATION TO COLLECTING NATURAL HISTORY STUDY DATA OVER THE PAST TWO DECADES PROVED INSTRUMENTAL IN THE APPROVAL OF THE FIRST-EVER TREATMENT FOR FA. THROUGH THE FA GLOBAL CLINICAL CONSORTIUM (FA GCC), FARA HAS REDOUBLED ITS INVESTMENT IN NATURAL HISTORY DATA BY ENABLING THE TRANSITION TO AN INDUSTRY-LEADING DATA COLLECTION PLATFORM AND A UNIFIED GLOBAL NATURAL HISTORY PROTOCOL (UNIFAI) RESULTING FROM THE HARMONIZATION OF TWO WELL-ESTABLISHED NATURAL HISTORY STUDIES, THE FA CLINICAL OUTCOME MEASURES STUDY (FA-COMS) AND THE EUROPEAN FRIEDREICH'S ATAXIA CONSORTIUM FOR TRANSLATIONAL STUDIES (EFACTS). THE FA GCC AND THE UNIFAI STUDY HAVE BEEN EXPANDED TO MAKE PATIENT CONTRIBUTIONS TO NATURAL HISTORY EVEN MORE POWERFUL IN UNDERSTANDING FA, EVALUATING THE IMPACT OF TREATMENT OPTIONS FOR FA, ACCELERATING THE DEVELOPMENT OF NEW THERAPIES AND IMPROVING OUTCOMES FOR THOSE LIVING WITH FA. AT EACH UNIFAI STUDY VISIT THERE ARE MORE THAN 1400 DATA ELEMENTS RECORDED. IN 2023, THE FA GCC HAD ACTIVE PARTICIPATION FROM 54 INVESTIGATORS FROM 33 SITES REPRESENTING 18 COUNTRIES ALONG WITH REPRESENTATIVES FROM PATIENT ADVOCACY AND RESEARCH ORGANIZATIONS. FA GCC RESEARCH ACTIVITIES: THE FA GCC LEADERSHIP IDENTIFIED INITIAL SCIENTIFIC PRIORITIES AND CREATED WORKGROUPS TO ADDRESS THESE PRIORITIES. THE FOLLOWING WORK GROUPS, EACH MADE UP OF 5-10 CONSORTIUM MEMBERS, MET REGULARLY TO ADDRESS GAPS IN CURRENT FA RESEARCH: CARDIAC NATURAL HISTORY, LATE-STAGE SYMPTOMS, PEDIATRIC / PRESYMPTOMATIC, BIO-SAMPLES, MOOD AND COGNITION, AND PATIENT ADVOCACY/ADVISORY TEAM. IMPACT AND FUTURE DIRECTION: THE CONSORTIUM HAS A LONG-TERM OBJECTIVE OF FOSTERING MULTILATERAL RESEARCH AND COLLABORATION ACROSS CONTINENTS, UNIFYING GLOBAL OPINIONS TO REGULATORS AND INDUSTRY PARTNERS, ACCELERATING THE DEVELOPMENT OF NEW THERAPIES, AND IMPROVING OUTCOMES FOR THOSE LIVING WITH FA. ADDITIONAL INFORMATION ABOUT FARA'S PROGRAMS IN 2023 CAN BE ACCESSED VIA THE ANNUAL REPORT AT: CUREFA.ORG