Congressional Directed Medical Research Program (CDMRP)
Add Your Support to FARA and NAF's CDMRP Initiative!

We are excited to share one of our recent advocacy efforts with you today. For the last year, FARA and NAF have been working towards getting “hereditary ataxia” added to the Congressionally Directed Medical Research Program (CDMRP). If added, it would provide another funding resource for researchers.
 
We became aware of this opportunity late in the Fiscal Year 22 appropriation process. Representative Chrissy Houlahan (D-PA), on our request, submitted an appropriation request to the House Defense subcommittee but unfortunately, we did not have time to build enough support to get it into the final bill. Our plan was to build a coalition of support this year and try again for the FY23 budget.
 
However, we have recently learned that there may be another option. Once the FY22 budget is approved, any Member of Congress can make a request to the Director of the CDMRP to redirect funds from their general account to a specific research project. We are now working with several Senate and House offices to secure a lead for this effort.
 
We are asking for your support in this effort by signing onto letters of support. We are attaching two templates for your review. The first is a sample letter that could be given to any Member of Congress regarding our current effort to redirect funds. The second is a sample letter to the Chairs and Ranking Members of the House and Senate Defense Appropriation subcommittee addressing the FY23 budget appropriation process. 
 
 
 
Click here to add your support to both letters!

We are encouraged about the potential opportunity this program could bring to your research program and the ataxia community overall. Stay tuned for updates.
ICAR 2022 Keynote Address from
Robert Brown, D.Phil, MD 
While our organizations are working to bring you an exciting program for ICAR 2022 this Fall, join us virtually on March 15th at 11am EST to hear the keynote address from Dr. Robert Brown, Leo P. and Theresa M. LaChance Chair in Medical Research and Director of the Program in Neurotherapeutics at UMass Medical School. 

If you wish to attend the keynote address, register here
Pharma News
Reata Pharmaceuticals Fourth Quarter Financial Results and Update on Development Programs 
Reata Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company, announced financial results for the quarter and full year ended on December 31, 2021 and provided an update on the Company’s business operations and clinical development programs. “We are making important progress in our efforts to advance omaveloxolone for the treatment of patients with Friedreich’s ataxia (“FA”) including receiving Fast Track Designation from the U.S. Food and Drug Administration (“FDA”) and initiating rolling submission of our New Drug Application (“NDA”). As we continue to complete the submission of our NDA for omaveloxolone, we are also actively preparing for the commercial launch of the drug early next year,” said Warren Huff, Reata’s Chief Executive Officer. You can read the full press release here.
Design Therapeutics Announces FDA Clearance of Investigational New Drug Application for First GeneTAC™ Molecule for Friedreich Ataxia   
Design Therapeutics, Inc., a biotechnology company developing treatments for degenerative genetic disorders, announced that its Investigational New Drug Application (IND) for its lead candidate, DT-216, for the treatment of Friedreich ataxia (FA), was cleared by the U.S. Food and Drug Administration (FDA). The company is preparing to initiate a Phase 1 clinical trial of DT-216 to assess the safety, tolerability, pharmacokinetics, and frataxin (FXN) levels in patients with FA. Study enrollment is expected to begin in the coming weeks. DT-216 is a GeneTAC™ gene targeted chimera small molecule designed to specifically target the GAA repeat expansion mutation and restore FXN gene expression. You can read the press release here.
LEXEO Announces FDA Clearance of IND Application for LX2006 for Friedreich’s Ataxia Cardiomyopathy 
LEXEO Therapeutics, a clinical-stage gene therapy company advancing a diverse pipeline of adeno-associated virus (AAV)-based gene therapy candidates for genetically defined cardiovascular and central nervous system diseases, announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for LX2006. LX2006 is an AAV-based gene therapy candidate designed to intravenously deliver a functional frataxin gene, for the treatment of Friedreich’s ataxia cardiomyopathy. LEXEO plans to initiate this open-label, dose-escalation Phase 1/2 clinical trial of LX2006 in patients with FA cardiomyopathy in the middle of 2022. You can read the press release here.
Larimar Therapeutics Provides Update on CTI-1601 Clinical Program 
Larimar Therapeutics, Inc., a clinical-stage biotechnology company focused on developing treatments for complex rare diseases, today announced that it has received feedback from the U.S. Food and Drug Administration (FDA) regarding the clinical hold on Larimar’s CTI-1601 program. FDA stated it is maintaining its clinical hold at this time and that additional data is needed to resolve the clinical hold. Larimar is further analyzing previously completed studies, and is evaluating if additional studies are warranted. The Company also intends to engage FDA to determine how best to provide these data. You can read the press release here.
Retrotope announces Phase 2/3 trial of RT001 in FA did not successfully meet its endpoints 
FARA has been notified by Retrotope that the recently completed Phase 2/3 trial of RT001 in FA did not successfully meet its endpoints. The primary outcome measure was peak workload change from baseline to 11 months using cardiopulmonary exercise testing (CPET). There were also secondary outcome measures to further assess neurological outcomes and fatigue. Retrotope reports that there was no improvement in exercise measures or neurological outcomes assessed in the study. To read more, click here.
Meet the Community

In this section, we'll introduce you to people living with FA to help share the patient and family perspectives. This month we're honored to feature The Ataxian- a documentary about Team FARA’s participation in Race Across America and the resilience of the FA community. It is now available for free on Youtube.
Recent FA Publications
Whole genome sequencing for the diagnosis of neurological repeat expansion disorders in the UK: a retrospective diagnostic accuracy and prospective clinical validation study. 
Ibañez K, Polke J, Hagelstrom RT, Dolzhenko E, Pasko D, Thomas ERA, Daugherty LC, Kasperaviciute D, Smith KR; WGS for Neurological Diseases Group, Deans ZC, Hill S, Fowler T, Scott RH, Hardy J, Chinnery PF, Houlden H, Rendon A, Caulfield MJ, Eberle MA, Taft RJ, Tucci A; Genomics England Research Consortium. 

This study aimed to assess the performance of whole genome sequencing in the diagnosis of patients with neurological repeat expansion disorders. The authors retrospectively assessed the diagnostic accuracy of whole genome sequencing to detect the most common repeat expansion loci associated with neurological outcomes and prospectively examined the clinical accuracy of whole genome sequencing to detect repeat expansions in previously genetically tested and undiagnosed patients. Whole genome sequencing for the detection of repeat expansions showed high sensitivity and specificity, and it led to identification of neurological repeat expansion disorders in previously undiagnosed patients.  
A Standardized Pipeline for Examining Human Cerebellar Grey Matter Morphometry using Structural Magnetic Resonance Imaging. 
Kerestes R, Han S, Balachander S, Hernandez-Castillo C, Prince JL, Diedrichsen J, Harding IH. 

This paper presents a standardized pipeline for examining cerebellum grey matter morphometry that combines high-resolution, state-of-the-art approaches for optimized and automated cerebellum parcellation (Automatic Cerebellum Anatomical Parcellation using U-Net Locally Constrained Optimization; ACAPULCO) and voxel-based registration of the cerebellum (Spatially Unbiased Infra-tentorial Template; SUIT) for volumetric quantification. This freely available pipeline has broad applicability to a range of neurological diseases and is fully automated, with manual intervention only required for quality control of the outputs.
Mitochondrial Dynamics and Mitochondria-Lysosome Contacts in Neurogenetic Diseases.  
Pijuan J, Cantarero L, Natera-de Benito D, Altimir A, Altisent-Huguet A, Díaz-Osorio Y, Carrera-García L, Expósito-Escudero J, Ortez C, Nascimento A, Hoenicka J, Palau F. 

This study aims at understanding the consequences on the cellular phenotype and pathophysiology of neurogenetic diseases associated with defective mitochondrial dynamics. The authors compared the fibroblasts phenotypes of (i) patients carrying pathogenic variants in genes involved in mitochondrial dynamics such as DRP1, GDAP1, OPA1, and MFN2, and (ii) patients carrying mutated genes that affect mitochondria, but that are not directly involved in mitochondrial dynamic network, such as FXN, MED13, and CHKB.
SARS-CoV-2 attacks the weakest point - COVID-19 course in a pediatric patient with Friedreich's ataxia.  
Faltin K, Lewandowska Z, Małecki P, Czyż K, Szafran E, Kowalska-Tupko A, Mania A, Mazur-Melewska K, Jończyk-Potoczna K, Bobkowski W, Figlerowicz M. 

This article presents the course of COVID-19 in a 17-year-old boy with Friedreich's ataxia-induced hypertrophic cardiomyopathy. He required antiarrhythmic treatment and pharmacological and electrical cardioversion. Moreover, because of pneumonia requiring supplemental oxygen, remdesivir and convalescent plasma therapy were utilized in this patient.
Drug Repositioning in Friedreich Ataxia. 
Rufini A, Malisan F, Condò I, Testi R. 

In this review the authors describe recent efforts aimed at the identification of a therapy for Friedreich ataxia through drug repositioning, and discuss the limitation of such strategies.
Protein Mutations and Stability, a Link with Disease: The Case Study of Frataxin.  
Puglisi R. 

This review summarizes what is known about the most common point mutations identified in frataxin in heterozygous FRDA patients, their effects on frataxin structure and function and the consequences of its binding with partners.
MRI CNS Atrophy Pattern and the Etiologies of Progressive Ataxias.  
Mascalchi M. 

MRI-based CNS atrophy pattern was reviewed in 128 progressive ataxias. Spinal atrophy was identified in Friedreich's ataxia, cortical cerebellar atrophy in 5 acquired and 72 inherited ataxias, olivopontocerebellar atrophy in Multi-System Atrophy and 12 inherited ataxias. 
The FARA Forum Webinars
The FARA Forum is a monthly webinar featuring investigators who have been awarded FARA grants. The webinar is open to FARA grant awardees and it is held on the second Tuesday of every month. Here are the next dates: 

April 12, 2022 
12:00 PM ET Masimo Pandolfo, McGill University

May 10, 2022
6:00 PM ET Christina Cortez-Jugo, University of Melbourne
FARA Newly Awarded Research Grants  
General Research Grants 

Chad Heatwole, MD - University of Rochester Medical Center, NY 
LEOPARD-FA: Longitudinal Endpoint Optimization to Provide an Assessment of Relevant Drugs in Friedreich’s Ataxia 
Meetings of Interest to the FA Community
The Ataxia Global Initiative (AGI) is holding a webinar series called Young Investigator Initiative (YII). The next webinar “Standard clinical assessment in ataxia” will be held on Tuesday, March 29, 2022 at 9am CEST. You can register and find more information on upcoming webinars here.


Mitochondrial biochemistry in health and disease, March 27-30, 2022 Beaver Run Resort, Colorado
 
American Society of Gene & Cell Therapy, May 16-19, 2022 - Washington, D.C. 

Neurodegeneration: The Biological Pathways Driving the Future of Therapeutic Development, Joint Meeting with Neuro-Immune Interactions in the Central Nervous System, Keystone CO June 05 - 09, 2022 
Grant Opportunities
  • General Research Grants – next LOI deadline is August 15, 2022. See FARA grant program priorities here.

The Chan Zuckerberg Initiative invites applications from collaborative teams bringing together patient-led rare disease organizations and research teams for 4-year research projects aimed at advancing our understanding of the fundamental science of rare diseases. 
  • RFA for Patient-Partnered Collaborations for Single-Cell Analysis of Rare Inflammatory Pediatric Disease – application deadline is May 24, 2022. 
  • RFA for Patient-Partnered Collaborations for Rare Neurodegenerative Disease – application deadline is May 24, 2022.  

CIRM - Various grant opportunities for stem cell-related projects in California.

Wellcome Trust funding opportunities. Application deadlines: Wellcome Discovery - Mar 24, 2022, Wellcome Career Development Awards - Mar 29, 2022. 
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