FARA Flash Talks
FARA is proud to announce the 4 winners for best presentations of the FA Research Flash Talks series that took place in May: 

  • Jaclyn Tamaroff, Children’s Hospital of Philadelphia
  • Joseph Rainaldi, University of California San Diego
  • Julia Dunn, Children’s Hospital of Philadelphia
  • Jamison Seabury, University of Rochester

These webinars featured Young Investigators from FARA funded laboratories around the world. Each session covered the different types of research that FARA funds; from basic research on understanding the disease, to examples of therapeutic approaches, biomarker and clinical research. The webinar sessions were attended by individuals with FA, caregivers, and researchers. We are grateful to all of the young scientists who participated, to the moderators for helping with the discussion and adding their own perspective on the studies presented, and to the audience for engaging with the presenters. To view the recordings of the four sessions, click here. 
Pharma News
Reata Announces that The FDA Has Asked The Company to Request a Pre-NDA Meeting for Omaveloxolone for the Treatment of Friedreich’s Ataxia 

Reata Pharmaceuticals announced that it received a communication from the Division of Neurology Products 1 (“Division”) of the U.S. Food and Drug Administration (“FDA”) stating that, after a preliminary review of briefing materials for an upcoming Type C meeting, a pre-NDA meeting is the most appropriate format for a discussion of the development program for omaveloxolone in Friedreich’s ataxia (“FA”). The Division asked the Company to focus the new briefing package on questions, issues, and needs applicable to a pre-NDA meeting. 
Larimar Therapeutics Reports Positive Topline Phase 1 Clinical Trial Data Showing Dose-Dependent Increases in Frataxin Levels in Patients with Friedreich’s Ataxia 

Larimar Therapeutics, Inc. announced topline data from its Phase 1 multiple ascending dose (MAD) clinical trial (n=27) evaluating CTI-1601 as a treatment for FA. 

FA patients participating in the trial received subcutaneous injections of CTI-1601 or placebo at increasing dose levels and frequencies over a 13-day period. Data show that repeated subcutaneous administration of CTI-1601 resulted in dose-dependent increases in frataxin (FXN) levels from baseline compared to placebo controls. These dose-dependent increases in frataxin levels were seen in all evaluated tissues (buccal cells, skin biopsies, and platelets) with daily dosing. Safety data from the trial indicate that repeated subcutaneous injections of CTI-1601 were generally well tolerated at doses up to 100 mg administered daily for 13 days. 
Larimar Therapeutics Receives European Medicines Agency Priority Medicines (PRIME) Designation for CTI-1601 in Friedreich’s Ataxia
 
Larimar Therapeutics, Inc. announced that the European Medicines Agency (EMA) has granted Priority Medicines (PRIME) designation to CTI-1601 for the treatment of FA. CTI-1601 is a recombinant fusion protein intended to deliver human frataxin into the mitochondria of patients with FA who are unable to produce enough of this essential protein. The PRIME designation was based on positive data from Larimar’s nonclinical studies and Phase 1 clinical program in patients with FA. The PRIME program is designed to enhance support for the development of medicines that target an unmet medical need. Through PRIME, the EMA offers early and proactive support to medicine developers to optimize the generation of robust data on a medicine’s benefits and risks and enable accelerated assessment of medicines applications so that these medicines can reach patients earlier. 
Larimar Therapeutics Reports FDA Clinical Hold on CTI-1601 and Termination of Recently Announced Private Placement Financing 

Larimar Therapeutics, Inc. announced that the United States Food and Drug Administration (FDA) has placed a clinical hold on the CTI-1601 clinical program and that the company will not be closing a previously announced private placement financing. The clinical hold follows the previous notification by Larimar to the FDA of mortalities which occurred at the highest dose levels in an ongoing 180-day non-human primate (NHP) toxicology study, which is designed to support extended dosing of patients with CTI-1601. In the clinical hold letter, the FDA stated it needs a full study report from the ongoing NHP study and Larimar may not initiate additional clinical trials until the company has submitted the report and received notification from the agency that additional clinical trials may commence.  
FARA Funded Research, May 2021
Drp1-dependent peptide reverse mitochondrial fragmentation, a homeostatic response in Friedreich ataxia. 
Johnson J, Mercado-Ayón E, Clark E, Lynch D, Lin H. 

This paper demonstrates that frataxin deficiency causes excessive mitochondrial fragmentation that is dependent upon Drp1 activity in Friedreich ataxia cellular models. Drp1 inhibition by the small peptide TAT-P110 reverses mitochondrial fragmentation but also decreases ATP levels in frataxin-knockdown fibroblasts and FRDA patient fibroblasts, suggesting that fragmentation may provide a homeostatic pathway for maintaining cellular ATP levels. The cardiolipin-stabilizing compound SS-31 similarly reverses fragmentation through a Drp1-dependent mechanism, but it does not affect ATP levels.   
Scoliosis in Friedreich's ataxia: longitudinal characterization in a large heterogeneous cohort. 
Rummey C, Flynn JM, Corben LA, Delatycki MB, Wilmot G, Subramony SH, Bushara K, Duquette A, Gomez CM, Hoyle JC, Roxburgh R, Seeberger L, Yoon G, Mathews KD, Zesiewicz T, Perlman S, Lynch DR. 

The objective of this study was to characterize the incidence and progression of scoliosis in the natural history of Friedreich's ataxia (FRDA) and document the factors leading to the requirement for corrective surgery. Data on the prevalence of scoliosis and scoliosis surgery from up to 17 years of follow-up collected during a large natural history study in FRDA (1116 patients at 4928 visits) were summarized descriptively and subjected to time to event analyses. Well over 90% of early or typical FRDA patients (as determined by age of onset) developed intermediate to severe scoliosis, while patients with a later onset (>14 years) had no or much lower prevalence of scoliosis. Major progression follows throughout the growth phase and puberty, leading to the need for surgical intervention in more than 50% of individuals in the most severe subgroup.
Reverse phase protein array reveals correlation of retinoic acid metabolism with cardiomyopathy in Friedreich's ataxia. 
Napierala JS, Rajapakshe K, Clark A, Chen YY, Huang S, Mesaros C, Xu P, Blair IA, Hauser LA, Farmer J, Lynch DR, Edwards DP, Coarfa C, Napierala M. 

This study utilized a sensitive and high-throughput proteomic technique, reverse phase protein array (RPPA), to attain protein expression profiles of primary fibroblasts obtained from Friedreich's ataxia (FRDA) patients and unaffected controls. Among sixty-two fibroblast samples (44 FRDA and 18 controls) analyzed, 30 proteins/phosphoproteins were significantly changed in FRDA fibroblasts compared to control cells (p<0.05), mostly representing signaling molecules and metabolic enzymes. Results identified altered expression of members of the integrin family of proteins specifically associated with hearing loss in FRDA. Also, RPPA data, combined with results of transcriptome profiling, uncovered defects in the retinoic acid (RA) metabolism pathway in FRDA samples.
Other FA Research Publications, April 2021
Results of a randomized double-blind study evaluating luvadaxistat in adults with Friedreich ataxia. 
Wang H, Norton J, Xu L, DeMartinis N, Sen R, Shah A, Farmer J, Lynch D. 

This phase 2, randomized, double-blind, placebo-controlled, parallel-arm study evaluated the efficacy and safety of oral luvadaxistat (also known as TAK-831; NBI-1065844) in adults with FRDA. Adult patients with FRDA were randomized 2:1:2 to placebo, luvadaxistat 75 mg twice daily (BID), or luvadaxistat 300 mg BID for 12 weeks. For the primary endpoint, there was no statistically significant difference in change from baseline on the 9-HPT-1 (seconds-1 ) at week 12 between placebo (0.00029) and luvadaxistat 75 mg BID (-0.00031) or luvadaxistat 300 mg BID (-0.00059). Luvadaxistat was safe and well tolerated; the majority of reported adverse events were mild in intensity.  
Newly Funded FARA Research Grants
General Research Grants
Postdoctoral fellowship
Rucha Sarwade - Monash University, Australia, 
Investigating epigenetic silencing in Friedreich's Ataxia

co-sponsor: fara Australia
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. Upcoming Dates:
 

June 8, 2021 
12:00 PM ET Tslil Ast, Mootha lab, Broad Institute 
12:45 PM ET Joshua Meisel, Mootha lab, Broad Institute 

July 13, 2021 
12:00:00 PM ET Javier Santos, Universidad de Buenos Aires 
12:45:00 PM ET Jaclyn Tamaroff, The Children's Hospital of Philadelphia 

August 10, 2021 
12:00:00 PM ET Sara Anjomani Virmouni, Brunel University
12:45:00 PM ET Vijay Chandran, University of Florida
Meetings of Interest to the FA Community
ISSCR June 21-26 - Virtual meeting

RNA Therapeutics Symposium, June 23-25, 2021 – Virtual meeting

Genome Engineering: CRISPR Frontiers August 18-20, 2021 - Virtual meeting

Save the date for the inaugural International Congress for Ataxia Research (ICAR), March 15-18, 2022 - Orlando, Florida, USA.
Grant Opportunities
FARA research grants – General grants – next LOI deadline is July 1, 2021. See the 2021 FARA grant program priorities here.

FARA RFP: Pharmacodynamic Biomarker Development – This RFP promotes the discovery of technologies to measure frataxin or surrogates of frataxin in inaccessible tissues. The LOI submission deadline is July 1, 2021. Access the full RFP here.

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

Wellcome Trust Innovator Award (UK) - Funding focus: development of diagnostics and repurposed medicines for neurological disorders including rare diseases. No deadline. 
Job Advertisements
Post-doctoral fellow position - Napierala Laboratory, University of Alabama at Birmingham

A post-doctoral fellow position is immediately available to study mechanisms of Friedreich’s ataxia in the Napierala Laboratory, within the Department of Biochemistry and Molecular Genetics at the University of Alabama at Birmingham. We are seeking a highly motivated scientist to join our multi-disciplinary group who is interested in investigating how chromatin changes are implicated in the pathogenesis of repeat expansion diseases.

The position requires experience utilizing mammalian cell culture models, and proficiency working with induced pluripotent stem cells is desirable. Preference will be given to candidates demonstrating expertise in chromatin biology, transcriptional regulation and post-translational histone modifications, including experience performing ChIP, ChIP-seq and RNAseq experiments.

The postdoctoral fellow duties will include but are not limited to: organizing and implementing complex research plans (independently and as part of a team), developing new methods, collecting and recording data, and analyzing and critically interpreting data. The successful candidate will be expected to possess excellent communication skills and present their research findings regularly to peers within the Department and at national and international meetings. The postdoctoral fellow will also participate in preparation of grant applications and publications.

We offer competitive pay at or above NIH recommended level and relocation assistance.

To be considered for this position, please email your CV and cover letter to mnapiera@uab.edu.
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