Tuesday, January 7, 2025

Solid Biosciences Announces FDA IND Clearance for First-In-Industry Dual Route of Administration Gene Therapy to Treat Both Neurologic and Cardiac Manifestations of Friedreich’s Ataxia

CHARLESTOWN, Mass., Jan. 07, 2025 (GLOBE NEWSWIRE) -- Solid Biosciences Inc. today announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for SGT-212 for the treatment of Friedreich’s ataxia (FA). SGT-212 is the Company’s novel, AAV-based FA gene therapy candidate designed to deliver full-length frataxin via systemic intravenous (IV) infusion as well as direct intradentate nuclei (IDN) infusion into the cerebellum. SGT-212 is designed to treat the neurologic and systemic clinical manifestations of FA to address the full spectrum of disease progression. 

In the second half of 2025, the Company expects to initiate a first-in-human, open-label, dose-finding Phase 1b clinical trial of SGT-212. The study will enroll non-ambulatory and ambulatory adult patients living with FA across up to three cohorts and will evaluate the safety and tolerability of contemporaneous systemic and bilateral IDN administration of SGT-212. Participants in the trial will be followed out to five years after receiving SGT-212.

Sunday, January 5, 2025

Triplex H-DNA structure: the long and winding road from the discovery to its role in human disease

Hisey JA, Masnovo C, Mirkin SM. Triplex H-DNA structure: the long and winding road from the discovery to its role in human disease. NAR Mol Med. 2024 Dec 5;1(4):ugae024. doi: 10.1093/narmme/ugae024. PMID: 39723156; PMCID: PMC11667243. 

H-DNA-forming repeats have been implicated in four REDs: Friedreich's ataxia, GAA-FGF14-related ataxia, X-linked Dystonia Parkinsonism, and cerebellar ataxia, neuropathy and vestibular areflexia syndrome. In this review, we summarize H-DNA's discovery and characterization, evidence for its existence and function in vivo, and the field's current knowledge on its role in physiology and pathology.

Harshly Oxidized Activated Charcoal Enhances Protein Persulfidation with Implications for Neurodegeneration as Exemplified by Friedreich's Ataxia

Vo ATT, Khan U, Liopo AV, Mouli K, Olson KR, McHugh EA, Tour JM, Pooparayil Manoj M, Derry PJ, Kent TA. Harshly Oxidized Activated Charcoal Enhances Protein Persulfidation with Implications for Neurodegeneration as Exemplified by Friedreich's Ataxia. Nanomaterials (Basel). 2024 Dec 13;14(24):2007. doi: 10.3390/nano14242007. PMID: 39728543. 

We demonstrate that pleozymes increased overall protein persulfidation in cells from apparently healthy individuals and from individuals with the mitochondrial protein mutation responsible for Friedreich's ataxia. We further find that pleozymes specifically enhanced Keap1 persulfidation, with subsequent increased accumulation of Nrf2 and Nrf2's antioxidant targets.