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.

Guía de Evaluación Diagnóstica y Discapacidad en Pacientes con Ataxias y Paraparesias Espásticas Hereditarias

Francisco Javier Arpa Gutiérrez, María José Abenza Abildúa, Idoia Rouco Axpe. Sociedad Española de Neurología (2022). ISBN: 978-84-124320-4-6 . https://www.edicionessen.es

El objetivo de este trabajo, dirigido a neurólogos en general y a otros facultativos de especialidades médicas como medicina física y rehabilitadora, atención primaria, medicina interna, medicina del trabajo, etc., es facilitar la correcta valoración diagnóstica y de la discapacidad en los pacientes con AH y PEH. Una gradación completa y homogénea de su situación clínica aumentaría la posibilidad de acceder a recursos sociales y legales adecuados a su situación.

The Use of Enhanced Recovery After Surgery Protocols and Sugammadex in a Friedreich Ataxia Patient Who Underwent Robotic Surgery: A Case Report of a Patient Who Required No Postoperative Opioids and Was Discharged Home Earlier Than Anticipated

Lori P. Russo, Daniel Haddad, Daniel Bauman, Mina M. Fam (September 26, 2022). Cureus 14(9): e29590. doi:10.7759/cureus.29590

Anesthesia in general must be carefully planned in FRDA patients to allow for the best possible recovery and minimize complications. Due to the underlying neuromuscular compromise seen in these patients, their ability to recover from the pharmacologic and physiologic changes associated with anesthesia can be more difficult. They are prone to sensitivity to opioids, sedatives, and neuromuscular blocking agents (NMBAs) and are less likely to tolerate hemodynamic changes. Our review revealed no literature to suggest the routine use of Enhanced Recovery After Surgery (ERAS) protocols in FRDA patients or in patients with neuromuscular disease in general. The use of sugammadex has also been shown to be safe, and literature suggests superiority in both the general population and those with neuromuscular conditions. Our understanding is that there is very limited literature in regard to the safe use of sugammadex in FRDA patients.

The inherited cerebellar ataxias: an update

Coarelli G, Wirth T, Tranchant C, Koenig M, Durr A, Anheim M.; J Neurol. 2022 Sep 24. doi: 10.1007/s00415-022-11383-6. 

We describe new therapeutic leads: antisense oligonucleotides approach in polyglutamine SCAs and viral gene therapy in Friedreich ataxia. This review provides support for diagnosis, genetic counseling and therapeutic management of ICAs in clinical practice.

Diagnostic Delay and Clinical Features in Friedreich’s Ataxia

Mehmet Fatih Yetkin, Murat Gültekin, Merve Akcakoyunlu, Recep Baydemir, Ayse Çağlar Sarılar, Mehmet Canpolat, Hüseyin Per; Turk Noroloji Dergisi, cilt.28, sa.2, ss.97-101, 2022 (Hakemli Dergi). DOI:10.4274/tnd.2022.26780

Conclusion: This study is the first study to evaluate the diagnosis delay in patients with FRDA in our country. Although FRDA was the most common hereditary ataxia, in our study, it was shown that there was a significant delay in diagnosis in patients with FRDA. There is a need for studies that will raise awareness of public and health professionals about FRDA.

FRIEDREICH'S ATAXIA AND ITS CARDIOVASCULAR MANIFESTATIONS

Bryam Esteban Coello Garcia, Karina Noemi Contreras Garcia, Priscila Jazmin Sarango Lapo, Tatiana Carolina Espinoza Coyago, Johanna Belen Illescas Aguilera, Bonny Maria Montalvan Nivicela, Karen Sofia Suscal Pelaez; EPRA International Journal of Multidisciplinary Research (IJMR) -Volume: 8, Issue: 9, September 2022, DOI:10.36713/epra11261 

 The aim of this bibliographic review is to inform the scientific community of the presence of systemic manifestations, especially cardiovascular, in Friedreich's Ataxia; since this disease is not only characterized by the presence of neurological alterations, but also of affections to different apparatuses and systems of the human body, such as the heart, due to the cellular alteration that Friedreich's Ataxia causes.