The present review aims at recapitulating all the open questions that Yfh1 has helped to address, including understanding the differences and commonalities of the cold, heat and pressure unfolded states. This protein thus offers a unique tool for studying aspects of protein stability so far been considered difficult to assess and provides important guidelines that could allow the identification of other similar systems.
Tuesday, January 14, 2025
Life and death of Yfh1: how cool is cold denaturation
Temussi PA, Martin SR, Pastore A. Life and death of Yfh1: how cool is cold denaturation. Q Rev Biophys. 2025 Jan 13;58:e2. doi: 10.1017/S0033583524000180. PMID: 39801016.
Monday, January 13, 2025
Longitudinal analysis of anthropometric measures over 5 years in patients with Friedreich ataxia in the EFACTS natural history study
Lischewski SA, Konrad K, Dogan I, Didszun C, Costa AS, Schawohl SA, Giunti P, Parkinson MH, Mariotti C, Nanetti L, Durr A, Ewenczyk C, Boesch S, Nachbauer W, Klopstock T, Stendel C, de Rivera Garrido FJR, Schöls L, Fleszar Z, Klockgether T, Grobe-Einsler M, Giordano I, Rai M, Pandolfo M, Schulz JB, Reetz K; EFACTS study group. Longitudinal analysis of anthropometric measures over 5 years in patients with Friedreich ataxia in the EFACTS natural history study. Eur J Neurol. 2025 Jan;32(1):e70011. doi: 10.1111/ene.70011. PMID: 39797559; PMCID: PMC11724196.
Significant anthropometric abnormalities were identified, with underweight and short stature prevalent in children and overweight in adults. These findings highlight the need for regular nutritional monitoring and interventions to manage underweight in children and promote healthy weight in adults.
Friday, January 10, 2025
Effects of physiotherapy on degenerative cerebellar ataxia: a systematic review and meta-analysis
Matsugi A, Bando K, Kondo Y, Kikuchi Y, Miyata K, Hiramatsu Y, Yamanaka Y, Tanaka H, Okuda Y, Haruyama K and Yamasaki Y (2025) Effects of physiotherapy on degenerative cerebellar ataxia: a systematic review and meta-analysis. Front. Neurol. 15:1491142. doi: 10.3389/fneur.2024.1491142
Physical therapy, especially multi-aspect physical therapy such as muscle strengthening, coordination training, gait training, and ADL training, may reduce DCA symptoms. Further, balance and aerobic training can be added to the program. However, the estimated effect size may change in future studies because of the serious RoB, very low certainty of evidence, and high heterogeneity with SARA as the primary outcome. High-quality RCTs are required to establish evidence for the effectiveness of physical therapy in patients with DCA.
Poincaré plot analysis of ECG uncovers beneficial effects of omaveloxolone in a mouse model of Friedreich’s ataxia
Poincaré plot analysis of ECG uncovers beneficial effects of omaveloxolone in a mouse model of Friedreich’s ataxia, Figueroa, Francisco et al., Heart Rhythm, Volume 0, Issue 0. DOI: 10.1016/j.hrthm.2024.12.041
Our study revealed significant electrical propagation disturbances and sexual dimorphism in FXN-cKO mice with severe cardiomyopathy. Poincaré plots identified irregularities in heart rhythm and ANS dysfunction. OMAV improved heart function by stabilizing early repolarization and reducing disparate arrhythmias. This work stresses sex-specific ECG interpretations and alternative mathematical approaches for drug testing in FA models.
Wednesday, January 8, 2025
Capsida Announces AbbVie Opt-in for First Genetic Medicine Program from Neurodegenerative Disease Collaboration
THOUSAND OAKS, Calif., Jan. 7, 2025 /PRNewswire/ -- Capsida Biotherapeutics ("Capsida") today announced that AbbVie has exercised an option for the first neurodegenerative disease program under their ongoing collaboration. Capsida will receive a $40 million license payment and is eligible for additional milestones and royalties.
Capsida's wholly owned pipeline includes a potential first-in-class treatment for STXBP1 developmental and epileptic encephalopathy, best-in-class treatment for Parkinson's disease associated with GBA mutations, and best-in-class therapy for Friedreich's ataxia. In addition to its wholly owned programs, the Company has validating partnerships with AbbVie, Lilly, and CRISPR Therapeutics.
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.
Tuesday, December 31, 2024
Safety and efficacy of omaveloxolone v/s placebo for the treatment of Friedreich's ataxia in patients aged more than 16 years: a systematic review
Umrao, A., Pahuja, M. & Chatterjee, N.S. Safety and efficacy of omaveloxolone v/s placebo for the treatment of Friedreich's ataxia in patients aged more than 16 years: a systematic review. Orphanet J Rare Dis 19, 495 (2024). doi:10.1186/s13023-024-03474-6
The results of the Omav treatment indicated a persistent benefit to FA patients who received Omav for an extended period. The greater effect on longer GAA lengths than shorter repeats and the lower degree of improvement in pes cavus patients suggest that Omav aims for the most severe or progressive abnormalities in FA patients in a time-dependent manner.
Therefore, based on the available literature and the quality of the studies, further randomized controlled trials may include patients with progressive disease with the consideration of pes cavus, foot deformity. Considering the progressive nature of the disease, long-term follow-up beyond three years to constantly evaluate the effect of Omav on FA patients shall be considered.
Health-Related Quality of Life in Patients with Friedreich Ataxia Using Mobility Assistive Technologies: Limited Fit of the EQ-5D-3L Mobility Dimension
Health-Related Quality of Life in Patients with Friedreich Ataxia Using Mobility Assistive Technologies: Limited Fit of the EQ-5D-3L Mobility Dimension. Maresa Buchholz, Michelle Pfaff, Audrey Iskandar, Kathrin Reetz, Jörg B. Schulz, Marcus Grobe-Einsler, Thomas Klockgether, Bernhard Michalowsky, EFACTS Study Group, Neurology and Therapy, Print ISSN: 2193-8253, Elektronische ISSN: 2193-6536, DOI: 10.1007/s40120-024-00694-7
There are concerns about using HRQoL measures, such as the EQ-5D, in mobility-impaired individuals who had difficulties finding appropriate response options for mobility-related items. Our findings demonstrated limitations of the EQ-5D-3L mobility item in patients with FA using MAT, detecting a noticeable amount of non-responses in the mobility item in wheelchair users and a tendency to the mid-response level “some problems” in individuals using walking aids.
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