An Overview of the Ferroptosis Hallmarks in Friedreich’s Ataxia

Turchi, R.; Faraonio, R.; Lettieri-Barbato, D.; Aquilano, K. Biomolecules 2020, 10, 1489. doi:10.3390/biom10111489 

 Even though ferroptosis has been associated with various neurodegenerative diseases including FRDA, the mechanisms leading to disease onset/progression have not been demonstrated yet. We describe the molecular alterations occurring in FRDA that overlap with those characterizing ferroptosis. Major conclusions: The study of ferroptotic pathways is necessary for the understanding of FRDA pathogenesis, and anti-ferroptotic drugs could be envisaged as therapeutic strategies to cure FRDA.

Gene Therapy Company AavantiBio Launches With $107 Million Series A Financing From Perceptive Advisors, Bain Capital Life Sciences, RA Capital Management and Sarepta Therapeutics

CAMBRIDGE, Mass., Oct. 22, 2020 (GLOBE NEWSWIRE). 

 A premier syndicate of life sciences investors including Perceptive Advisors, Bain Capital Life Sciences (“Bain Capital”), and RA Capital Management (“RA Capital”) (collectively the “Investor Group”) together with Sarepta Therapeutics, Inc. (“Sarepta”) (NASDAQ: SRPT), a leader in precision genetic medicine for rare diseases, today announced a $107 million Series A financing to create AavantiBio, a gene therapy company focused on transforming the lives of patients with rare genetic diseases. The private financing round includes a $15 million equity investment from Sarepta.

Headquartered in the greater Boston area, UF startup and UF Innovate | The Hub resident client AavantiBio, is co-founded by renowned gene therapy researchers Barry Byrne, M.D., Ph.D., and Manuela Corti, P.T., Ph.D., who together bring thirty years of experience to the company. AavantiBio’s lead program is in Friedreich’s Ataxia (FA), a rare inherited genetic disease that causes cardiac and central nervous system dysfunction. AavantiBio’s research efforts expand on foundational research conducted by Drs. Byrne and Corti in Friedreich’s Ataxia, among other rare genetic disorders. AavantiBio will benefit from strategic partnerships with the University of Florida’s renowned Powell Gene Therapy Center and the MDA Care Center at UF Health where Drs. Byrne and Corti maintain their research and clinical practices. Initial funding in AavantiBio was provided by GoFAR, an Italian patient advocacy group, and the Muscular Dystrophy Association Venture Philanthropy Fund.

The French Association of Ataxia in Friedreich renews its 25,000 euro grant to validate the therapeutic potential of calcitriol for treating this rare malaltia

IRBLleida, Friday, October 23, 2020. The French Association of Ataxia of Friedreich has renewed the aid of 25,000 euros to the Oxidative stress biochemistry Research Group of the Biomedical Research Institute of Lleida (IRBLleida) and the University of Lleida (UdL) to validate the therapeutic potential of calcitriol, the active form of vitamin D, to treat this disease. "The entity has decided to continue collaborating due to the advances in research carried out in Lleida, despite the difficulties of working in the laboratory during the confinement and the new normality" explained the principal investigator of this project, Fabien Delaspre.

Sarepta, continuing its gene therapy push, helps launch a startup

BIOPHARMA DIVE, Oct. 22, 2020. AavantiBio joins a couple large, powerful companies in the hunt for a gene therapy to treat Friedreich's ataxia. Pfizer and Novartis are each working on their own programs. Outside of gene therapy, Reata Pharmaceuticals disclosed last year positive data from a study that tested an oral drug, known as omaveloxolone, in patients with Friedreich's ataxia. Reata said it intends to file the drug for approval based on those results.

Design Therapeutics Appoints Industry Veteran, Dr. João Siffert, as Chief Executive Officer

Design Therapeutics. San Diego, Calif., Oct. 20, 2020

Design Therapeutics, a biotechnology company developing a platform of gene targeted chimera (GeneTAC™) small molecules for the treatment of serious degenerative disorders caused by nucleotide repeat expansions, today announced that João Siffert, M.D., has been appointed as chief executive officer and will also join the Board of Directors. Dr. Siffert joins the founding Design Therapeutics team, including Pratik Shah, Ph.D., co-founder and executive chairman; Aseem Ansari, Ph.D., co-founder and director; and Sean Jeffries, Ph.D., chief business officer. Dr. Siffert brings extensive industry knowledge to Design, with 30 years combined experience in the biopharmaceutical industry, clinical practice and academia. 

 Design Therapeutics is a biotechnology company developing a new class of therapies based on a platform of gene targeted chimera (GeneTAC™) small molecules. The company’s lead program is focused on the treatment of Friedreich ataxia and discovery efforts are ongoing in other for serious degenerative disorders caused by nucleotide repeat expansions.

Assessment of Ataxia Rating Scales and Cerebellar Functional Tests: Critique and Recommendations

Perez-Lloret S, van de Warrenburg B, Rossi M, Rodríguez-Blázquez C, Zesiewicz T, Saute JAM, Durr A, Nishizawa M, Martinez-Martin P, Stebbins GT, Schrag A, Skorvanek M; and members of the MDS Rating Scales Review Committee; Mov Disord. 2020 Oct 6. doi: 10.1002/mds.28313

We identified some "recommended" scales and functional tests for the assessment of patients with major hereditary ataxias and other cerebellar disorders. The main limitations of these instruments include the limited assessment of patients in the more severe end of the spectrum and children. Further research in these populations is warranted.

Safety and Efficacy of Omaveloxolone in Friedreich's Ataxia (MOXIe Study)

Lynch, D.R., Chin, M.P., Delatycki, M.B., Subramony, S., Corti, M., Hoyle, J.C., Boesch, S., Nachbauer, W., Mariotti, C., Mathews, K.D., Giunti, P., Wilmot, G., Zesiewicz, T., Perlman, S., Goldsberry, A., O'Grady, M. and Meyer, C.J. (2020). Ann Neurol. Accepted Author Manuscript. doi:10.1002/ana.25934

In the MOXIe trial, omaveloxolone significantly improved neurological function compared to placebo and was generally safe and well tolerated. It represents a potential therapeutic agent in FRDA.

Reata Pharma Accused in Securities Suit of Hyping Drug Prospects

PHILADELPHIA, Oct. 16, 2020 (GLOBE NEWSWIRE) -- Kehoe Law Firm, P.C. is investigating potential securities claims on behalf of investors of Reata Pharmaceuticals, Inc. (“Reata” or the “Company”) (NASDAQ: RETA) to determine whether the Company engaged in securities fraud or other unlawful business practices. Omaveloxolone, according to the complaint, is “[a]mong Reata’s drug candidates under development . . . which is in Phase 2 clinical development to treat Friedreich’s ataxia (‘FA’). Following the announcement of positive data from the MOXIe Part 2 study of omaveloxolone for FA in October 2019, the Company represented that it would seek submission for marketing approval of omaveloxolone for the treatment of FA in the [United States] with the U.S. Food and Drug Administration (‘FDA’).” The Reata Defendants, according to the complaint, made false and/or misleading statements and/or failed to disclose that: (i) the MOXIe Part 2 study results were insufficient to support a single study marketing approval of omaveloxolone for the treatment of FA in the United States without additional evidence.

Longitudinal Study of Cognitive Functioning in Friedreich’s Ataxia

Atteneri Hernández-Torres, Fernando Montón, Stephany Hess Medler, Érika de Nóbrega and Antonieta Nieto; Longitudinal Study of Cognitive Functioning in Friedreich’s Ataxia. DOI:10.1017/S1355617720000958 Published online by Cambridge University Press: 14 October 2020

At follow-up, cerebellar symptoms had worsened, and patients presented greater disability. Differences between baseline and follow-up were observed in motor and cognitive reaction times, several trials of the Stroop test, semantic fluency, and block designs. No other cognitive changes were observed. Deterioration in simple cognitive reactions times and block designs performance correlated with the progression of cerebellar symptoms. Our study has demonstrated for the first time that patients with FRDA experience a significant decline over time in several cognitive domains. Specifically, after an eight-year period, FRDA patients worsened in processing speed, fluency, and visuoconstructive skills. This progression is unlikely to be due to greater motor or speech impairment.

Larimar Therapeutics Announces Formation of Scientific Advisory Board

BALA CYNWYD, Pa., Oct. 13, 2020 (GLOBE NEWSWIRE) -- Larimar Therapeutics, Inc. (Nasdaq:LRMR), a clinical-stage biotechnology company focused on developing treatments for complex rare diseases, today announced the formation of its Scientific Advisory Board (SAB). Larimar’s SAB is comprised of distinguished research scientists, professors and industry experts recognized as key opinion leaders in the fields of rare disease, pediatrics and mitochondrial disease. “Larimar is privileged to have this group of prestigious, multidisciplinary advisors who are committed to advancing the research and development of CTI-1601 for Friedreich’s ataxia,”