Progressive Spinal Cord Degeneration in Friedreich's Ataxia: Results from ENIGMA-Ataxia

Thiago J.R. Rezende PhD, Isaac M. Adanyeguh PhD, Filippo Arrigoni MD, Benjamin Bender MD, Fernando Cendes MD, PhD, Louise A. Corben PhD, Andreas Deistung PhD, Martin Delatycki PhD, Imis Dogan PhD, Gary F. Egan PhD, Sophia L. Göricke MD, Nellie Georgiou-Karistianis PhD, Pierre-Gilles Henry PhD, Diane Hutter RN, Neda Jahanshad PhD, James M. Joers PhD, Christophe Lenglet PhD, Tobias Lindig MD, Alberto R.M. Martinez MD, PhD, Andrea Martinuzzi MD, PhD, Gabriella Paparella MD, Denis Peruzzo PhD, Kathrin Reetz MD, Sandro Romanzetti PhD, Ludger Schöls, Jörg B. Schulz MD, Matthis Synofzik MD, Sophia I. Thomopoulos BA, Paul M. Thompson PhD, Dagmar Timmann MD, Ian H. Harding PhD, Marcondes C. França Jr MD, PhD; (2022), Mov Disord. doi:10.1002/mds.29261 

The objective of this study was to perform a characterization of cervical spinal cord structural damage in a large multisite FRDA cohort. Previous research has shown that increased eccentricity reflects dorsal column (DC) damage, while decreased CSA reflects either DC or corticospinal tract (CST) damage, or both. Hence our data support the hypothesis that damage to the DC and damage to CST follow distinct courses in FRDA: developmental abnormalities likely define the DC, while CST alterations may be both developmental and degenerative. These results provide new insights about FRDA pathogenesis and indicate that CSA of the cervical spinal cord should be investigated further as a potential biomarker of disease progression.

Spinal cord magnetic resonance imaging and spectroscopy detect early-stage alterations and disease progression in Friedreich ataxia

James M Joers, Isaac M Adanyeguh, Dinesh K Deelchand, Diane H Hutter, Lynn E Eberly, Isabelle Iltis, Khalaf O Bushara, Christophe Lenglet, Pierre-Gilles Henry; Brain Communications, Volume 6, Issue 5, October 2022, fcac246, doi:10.1093/braincomms/fcac246

Graphical abstract

Larimar Therapeutics Announces Issuance of U.S. Patent Providing Composition of Matter Protection for CTI-1601

BALA CYNWYD, Pa., Oct. 20, 2022 (GLOBE NEWSWIRE) -- Larimar Therapeutics, Inc. (“Larimar”) (Nasdaq: LRMR), a clinical-stage biotechnology company focused on developing treatments for complex rare diseases, today announced the issuance of U.S. Patent No. 11,459,363. The patent, titled, “Materials and Methods for Treating Friedreich's Ataxia,” provides composition of matter protection for CTI-1601 into at least July 2040. Larimar has an exclusive license to the patent per a prior agreement with Indiana University.

Children with a rare congenital genetic disorder: a systematic review of parent experiences

von der Lippe, C., Neteland, I. & Feragen, K.B.; Orphanet J Rare Dis 17, 375 (2022). doi:10.1186/s13023-022-02525-0 

 Coordinated care, and a more holistic approach in the follow up of children with rare genetic disorders is needed. International collaboration on research, diagnostics, producing scientific correct and understandable information available for health care professionals and lay people should be prioritized.

Selection of Synthetic Proteins to Modulate the Human Frataxin Function

Pignataro MF, Herrera MG, Fernández N, Aran M, Gentili H, Bataglini F, Santos J.; Biotechnol Bioeng. 2022 Oct 12. doi: 10.1002/bit.28263. Epub ahead of print. PMID: 36225115. 

 Our results suggest quaternary addition may be a new tool to modulate frataxin function in vivo. Nevertheless, more functional experiments under physiological conditions should be carried out to evaluate Affi_224 effectiveness in FRDA cell models.

Reata Pharmaceuticals Announces that the FDA Does Not Plan to Hold an Advisory Committee Meeting to Discuss the NDA for Omaveloxolone for Friedreich’s Ataxia

October 13, 2022. PLANO, Texas--(BUSINESS WIRE)-- Reata Pharmaceuticals, Inc. (Nasdaq: RETA) (“Reata,” the “Company,” “our,” “us,” or “we”), a clinical-stage biopharmaceutical company, announced that the U.S. Food and Drug Administration (“FDA”) has informed the Company that it does not plan to hold an advisory committee meeting in connection with its review of the Company’s New Drug Application (“NDA”) for omaveloxolone for the treatment of patients with Friedreich’s ataxia.

Study to Evaluate Multiple Ascending Dose and Multi-Dose of DT-216 in Adult Patients With Friedreich Ataxia

ClinicalTrials.gov Identifier: NCT05573698. A Phase 1b, Randomized, Double-blind, Placebo-controlled, Multiple Ascending Dose and Multi-Dose Study of DT-216 in Adult Patients With Friedreich Ataxia. Recruitment Status : Recruiting

First Posted : October 10, 2022 

Sponsor: Design Therapeutics

SARS-CoV-2 in patients with Friedreich ataxia

Megan M. Shen, Layne N. Rodden, Kellie McIntyre, Adriana Arias, Victoria Profeta, Kimberly Schadt & David R. Lynch; J Neurol (2022). doi:10.1007/s00415-022-11419-x

On a broader scale, the pandemic’s effects on this cohort are likely more prominent not from infection itself but rather disruptions to physical activity and therapy services. Anecdotally, a substantial proportion of patients have perceived significant declines in global health resulting from these disruptions, consistent with previous reports [1]. Future investigation with an expanded cohort and updated vaccination data as novel SARS-CoV-2 variants emerge will continue to inform adaptations in care.

A promising mouse model for Friedreich Ataxia progressing like human patients

Catherine Gérard, Annabelle Fortin Archambault, Camille Bouchard, Jacques P. Tremblay; Behavioural Brain Research, Volume 436, 2023, 114107, doi:10.1016/j.bbr.2022.114107. 

Jackson Laboratories Inc. developed a new mouse model that has 800 GAA repeats. We demonstrate here that these mice accurately reflect the human disease with a progressive neuromuscular degeneration highlighted by the two beam tests and the beginning of heart hypertrophy at 26 weeks. YG8-800 mice are thus currently a promising mouse model for FRDA.

Diabetes mellitus y ataxia de Friedreich en un niño: una difícil coexistencia [Diabetes mellitus and Friedreich´s ataxia in a child: a complicated coexistence]

Marqués Cabrero A, Expósito Raspeño M, Sánchez Escudero V, Gutiérrez Cruz N, González Vergaz A.; Arch Argent Pediatr. 2022 Oct;120(5):e223-e225. Spanish. doi: 10.5546/aap.2022.e223. Epub 2022 Aug 30. PMID: 36190225. 

The appearance of motor clumsiness, with running and jumping difficulties in a 6-year-old boy prompted the genetic study of Friedreich's ataxia, confirming his diagnosis. After diagnosis, it was evaluated by Pediatric Cardiology, detecting the presence of non-obstructive hypertrophic cardiomyopathy, and by Pediatric Endocrinology, due to overweight. At 9 years of age, he was diagnosed with diabetes mellitus, a regimen of insulin treatment was initiated. During follow-up, he presented significant neurological deterioration, reaching the use of a wheelchair, which hinders adequate metabolic control. This is a report of a pediatric patient with Friedrich ataxia and diabetes mellitus.

Plasma multi-omics analysis reveals very long chain ceramides as validated biomarkers of Friedreich’s ataxia

Dezhen Wang, M. Grazia Cotticelli, Blanca E. Himes, David R. Lynch, Clementina Mesaros; medRxiv 2022.09.27.22280432; doi:10.1101/2022.09.27.22280432

 New plasma lipids biomarkers of Friedreich’s Ataxia (FRDA) were validated using a discovery-validation design with two independent cohorts.

Solid Biosciences Announces Acquisition of AavantiBio and Concurrent $75 Million Private Placement

September 30, 2022 07:00 ET | Source: Solid Biosciences Inc CHARLESTOWN, Mass. and CAMBRIDGE, Mass., Sept. 30, 2022 (GLOBE NEWSWIRE) -- Solid Biosciences Inc. (Nasdaq: SLDB), a life sciences company focused on advancing meaningful therapies for Duchenne muscular dystrophy (Duchenne), and AavantiBio, Inc., a privately-held gene therapy company focused on transforming the lives of patients with Friedreich’s ataxia and rare cardiomyopathies, today announced that the companies have entered into a definitive merger agreement whereby Solid will acquire AavantiBio, including its pipeline assets and net cash. The combined company will focus on advancing a portfolio of neuromuscular and cardiac programs, led by SGT-003, a differentiated gene transfer candidate, for the treatment of Duchenne. Additional pipeline programs include AVB-202, a gene transfer candidate for the treatment of Friedreich’s ataxia, AVB-401 for BAG3 mediated dilated cardiomyopathy, and additional assets for the treatment of undisclosed cardiac diseases. Following approval by Solid stockholders, the combined company will operate as Solid Biosciences, will trade on Nasdaq under the ticker symbol “SLDB” and Bo Cumbo, the current Chief Executive Officer of AavantiBio, will assume the role of President and CEO of Solid Biosciences. 

FA is a rare inherited neuromuscular disease that causes progressive nervous system damage and movement problems. AVB-202, AavantiBio’s lead AAV gene transfer therapy candidate in preclinical development, utilizes a dual route of administration to more rigorously target disease pathology. Preclinical data from three animal models, including mouse and nonhuman primate, supported preclinical proof of concept. Solid is anticipating an IND submission for AVB-202 in the second half of 2024.

Friedreich Ataxia: An expanded access program for Elamipretide treatment

Children's Mercy Kansas City / Children’s Mercy Research Institute. 

Full Study Name: SPIES-006

This study is for participants who are 1 to 80 years old and involves the treatment use of Elamipretide through the expanded access program for treatment of Friedreich Ataxia. This is a compassionate use study. Compassionate use studies are those where the drug is not available to the market and the sponsor is providing the drug to the patient without cost to them in hopes that it will help decrease the progression of their disease state.