Design Therapeutics Highlights Progress Across Lead GeneTAC® Programs

CARLSBAD, Calif., March 10, 2025 (GLOBE NEWSWIRE) -- Design Therapeutics, Inc. today announced progress across its portfolio of GeneTAC® candidates and reported fourth quarter and full year 2024 financial results.

Friedreich Ataxia (FA) Design has initiated dosing in a Phase 1 clinical trial in healthy volunteers in Australia to evaluate the safety and pharmacokinetics (PK) of single ascending doses of DT-216P2 via multiple routes of administration (intravenous infusion, subcutaneous infusion and subcutaneous injection). A Phase 1/2 multiple ascending dose (MAD) clinical trial to assess safety, PK and pharmacodynamics (PD) in FA patients is anticipated to begin in mid-2025. Data based on twelve weeks of DT-216P2 dosing in patients is anticipated in 2026.

FDA Action Update, February 2025: Approvals, Designations, and Acceptances

NeurologyLive. March 9, 2025. The FDA was busy in March 2025, making a number of decisions on potential new therapeutic agents including granting approvals, acceptances, and designations.

- Solid Biosciences' SGT-212 gene therapy for Friedreich ataxia received FDA clearance, targeting neurologic and systemic manifestations via dual administration routes. 

-On the same day, February 19, the FDA accepted PTC Therapeutics’ new drug application (NDA) for its investigational agent vatiquinone as a treatment for patients with Friedreich ataxia (FA)

Robust behavioral assessment of the inducible Friedreich's ataxia mouse does not show improvement with NRF2 induction

Claire B. Montgomery, Lili Salinas, Garrett P. Cox, Lauren E. Adcock, Tiffany Chang, Francisco Figueroa, Gino Cortopassi, Elena N. Dedkova; Robust behavioral assessment of the inducible Friedreich's ataxia mouse does not show improvement with NRF2 induction. Dis Model Mech 2025; dmm.052128. doi: https://doi.org/10.1242/dmm.052128

 We developed a novel Salinas-Montgomery Ataxia Scale (SMAS) which allows for more comprehensive assessment versus a 4-part cerebellar ataxia scale. Despite validating multiple sensitive techniques, we did not see any benefits of NRF2-inducing therapies in any tests. This was exacerbated by the discovery of a sexual dimorphism in FXNKD mice, in which males show a more significant decline and better responsiveness to NRF2-inducing therapeutics.

Solid Biosciences Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Updates

CHARLESTOWN, Mass., March 06, 2025 (GLOBE NEWSWIRE) -- Solid Biosciences Inc. SGT-212 for Friedreich’s ataxia (FA) As announced on January 7, 2025, the FDA has cleared the IND for SGT-212 for the treatment of FA. SGT-212 is the first gene therapy candidate to utilize a dual route of administration to treat FA. The Company expects to initiate a first-in-human, open-label, Phase 1b clinical trial of SGT-212 in the second half of 2025. The trial is expected to enroll non-ambulatory and ambulatory adult participants living with FA across up to three cohorts and is designed to evaluate the safety and tolerability of concurrent systemic and bilateral IDN administration of SGT-212.

Gait Characteristics in People with Friedreich Ataxia: Daily Life versus Clinic Measures

Hannah L. Casey • Vrutangkumar V. Shah • Daniel Muzyka • James McNames • Mahmoud El-Gohary • Kristen Sowalsky • Delaram Safarpour • Patricia (Patty) Carlson-Kuhta • Christian Rummey • Fay B. Horak • Christopher M. Gomez, Front. Neurol. Sec. Movement Disorders, Volume 16 - 2025 | doi: 10.3389/fneur.2025.1544453 

Digital gait characteristics from inertial sensors are sensitive and specific for FRDA in both environments. However, different gait measures were more sensitive and specific during free-living versus prescribed gait, suggesting that in-clinic gait does not reflect daily life gait.

A global perspective on research advances and future challenges in Friedreich ataxia

Indelicato, E., Delatycki, M.B., Farmer, J. et al. A global perspective on research advances and future challenges in Friedreich ataxia. Nat Rev Neurol (2025). doi:10.1038/s41582-025-01065-y

Nrf2 activators for the treatment of rare iron overload diseases: From bench to bedside

Dong Y, Zheng M, Ding W, Guan H, Xiao J, Li F. Nrf2 activators for the treatment of rare iron overload diseases: From bench to bedside. Redox Biol. 2025 Feb 14;81:103551. doi: 10.1016/j.redox.2025.103551. Epub ahead of print. PMID: 39965404.

 Despite these uses, the therapeutic potentials of Nrf2 activators for iron overload disorders may be overlooked in clinical practice. Therefore, this study talks about the potential use, possible mechanisms, and precautions of Nrf2 activators in treating rare iron overload diseases.

Effect of a Supratherapeutic Dose of Omaveloxolone on the Corrected QT Interval in Healthy Participants: A Randomized, Double-Blind, Placebo- and Active-Controlled, Three-Way Crossover Study

Zahir H, Murai M, Wu L, Valentine M, Hynes SM. Effect of a Supratherapeutic Dose of Omaveloxolone on the Corrected QT Interval in Healthy Participants: A Randomized, Double-Blind, Placebo- and Active-Controlled, Three-Way Crossover Study. Clin Transl Sci. 2025 Feb;18(2):e70139. doi: 10.1111/cts.70139. PMID: 39976332; PMCID: PMC11840845. 

No safety concerns were identified. Supratherapeutic omaveloxolone exposure that covers the worst-case clinical exposure did not cause a clinically significant QTc prolongation and was generally well tolerated.

Multiple Sclerosis in a Patient with Friedreich's Ataxia

Yu Y, Kushlaf H. Multiple Sclerosis in a Patient with Friedreich's Ataxia (P4-6.016). Neurology. 2024 Apr 9;102(7_supplement_1):3347. doi: 10.1212/WNL.0000000000205077. Epub 2024 Apr 9. PMID: 39977947. 

The definitive diagnosis of multiple sclerosis in a FRDA patient is novel and requires careful reconciliation of the symptoms, clinical exam findings, and ancillary testing. The development of symptoms incompatible with FRDA should prompt clinicians to consider additional neurologic diagnoses.

Healthcare delay in neurogenetic disorders of adult onset and the role of predictive genetic testing

Rocha, D.L., Pinheiro, J.d., Furtado, G.V. et al. Healthcare delay in neurogenetic disorders of adult onset and the role of predictive genetic testing. J Community Genet (2025). doi:10.1007/s12687-025-00777-4 

Healthcare delay (HCDe) is an important but not well-known issue in genetic disorders, especially in tandem nucleotide repeat expansion diseases (TNRED). We aimed to investigate it and determine whether predictive genetic testing (PGT) and other factors may impact HCDe.

Frataxin deficiency and the pathology of Friedreich's Ataxia across tissues

Ercanbrack WS, Ramirez M, Dungan A, Gaul E, Ercanbrack SJ, Wingert RA. Frataxin deficiency and the pathology of Friedreich's Ataxia across tissues. Tissue Barriers. 2025 Feb 21:2462357. doi: 10.1080/21688370.2025.2462357. Epub ahead of print. PMID: 39981684. 

Most FRDA patients suffer from loss of motor control, cardiomyopathy, scoliosis, foot deformities, and diabetes. In this review, we discuss the known features of FRDA pathology and the current understanding about the basis of these alterations.

FDA Accepts New Drug Application for Vatiquinone to Treat Friedreich Ataxia

February 19, 2025​. The FDA accepted a new drug application (NDA) for vatiquinone for the treatment of children and adults with Friedreich ataxia (FA) and granted it priority review. The drug has a Prescription Drug User Fee Act target action date of August 19, 2025. 

"The results of the extension studies provide further evidence of the potential benefit of vatiquinone in slowing disease progression," Klein said in a news release.4 "In addition, the strong safety profile of vatiquinone positions it to be a potentially meaningful therapy for all Friedreich ataxia patients, particularly children and adolescents for whom there are no approved therapies.”

Frataxin Traps Low Abundance Quaternary Structure to Stimulate Human Fe-S Cluster Biosynthesis

Cory SA, Lin CW, Patra S, Havens SM, Putnam CD, Shirzadeh M, Russell DH, Barondeau DP. Frataxin Traps Low Abundance Quaternary Structure to Stimulate Human Fe-S Cluster Biosynthesis. Biochemistry. 2025 Feb 5. doi: 10.1021/acs.biochem.4c00733. Epub ahead of print. PMID: 39909887.

We propose that eukaryotic cysteine desulfurases are unusual members of the morpheein class of enzymes that control their activity through their oligomeric state. Overall, the findings support architectural switching as a regulatory mechanism linked to FXN activation of the human Fe-S cluster biosynthetic complex and provide new opportunities for therapeutic interventions of the fatal neurodegenerative disease FRDA.

Clinical Assessment of the Drug-Drug Interaction Potential of Omaveloxolone in Healthy Adult Participants

Zahir H, Murai M, Wu L, Valentine M, Hynes S. Clinical Assessment of the Drug-Drug Interaction Potential of Omaveloxolone in Healthy Adult Participants. J Clin Pharmacol. 2025 Feb 7. doi: 10.1002/jcph.6189. Epub ahead of print. PMID: 39920097. 

 It is mainly metabolized by cytochrome P450 (CYP) 3A4 in vitro. Two drug-drug interaction studies (NCT04008186 and NCT05909644) were performed to evaluate (1) the effect of drug-metabolizing enzymes (DMEs) and drug transporter (DT) modulators on the pharmacokinetics of omaveloxolone and (2) the effect of omaveloxolone on the pharmacokinetics of DME and DT substrates. Additionally, the safety of coadministering these drugs with omaveloxolone was assessed.

Neurocrine Biosciences and Voyager Therapeutics to expect IND filings in 2025

February 13, 2025. 

“We are encouraged that our novel TRACER capsids continue to perform consistently across multiple programs, and we believe they have the potential to transform gene therapy for CNS diseases. We continue to expect IND filings in 2025 for our gene therapy candidates for GBA1 and FA, and in 2026 for VY1706,” said Sandrock, Jr., in the press release

Patient involvement in clinical trials: a paradigm shift in research

Pijuan, J., Palau, F. Patient involvement in clinical trials: a paradigm shift in research. Orphanet J Rare Dis 20, 63 (2025). doi:10.1186/s13023-025-03573-y 

 Establishing universal guidelines will help ensure that all stakeholders (patients, caregivers and health professionals) can engage meaningfully in the developmental processes of healthcare initiatives. Given that health and disease affect us all, fostering collective involvement is essential for driving progress in this field.

Living with Friedreich Ataxia: Carla, Maria and Nuria

Biogen. February 11, 2025

Watch below to hear Carla, Maria and Nuria share their stories of living with FA.

 

Editorial: The mechanistic investigation and emerging therapies for Friedreich’s ataxia

Dong Y, Chandran V, Soragni E and Lynch DR (2025) Editorial: The mechanistic investigation and emerging therapies for Friedreich’s ataxia. Front. Pharmacol. 16:1560808. doi: 10.3389/fphar.2025.1560808

KosBio is a pioneering biotechnology startup: to develop an innovative treatment for Friedreich’s Ataxia (FRDA)

KosBio is a pioneering biotechnology startup, born out of a deeply personal and transformative mission: to develop an innovative treatment for Friedreich’s Ataxia (FRDA), a rare and incurable neurodegenerative disease. Our founders, intimately connected to FRDA through their own family experiences, bring a unique level of commitment and dedication to this mission, distinguishing KosBio in the competitive biotech landscape. 

 Leading our therapeutic pipeline is KB-001(TM), a therapy based on repurposing an FDA-approved drug to activate a developmental signaling pathway relevant to FRDA. This strategic approach not only expedites the path to treatment but also reduces potential risks by leveraging existing approved drugs. 

In addition, KosBio is advancing the development of a series of novel, patented drugs (KB002-KB021). These drugs are projected to have significantly greater potency than KB-001(TM), marking a substantial advancement in our therapeutic arsenal.

Functional Characterization of Parallel Fiber-Purkinje Cell Synapses in Two Friedreich's Ataxia Mouse Models

Joseph DJ, Mercado-Ayon E, Flatley L, Viaene AN, Hordeaux J, Marsh ED, Lynch DR. Functional Characterization of Parallel Fiber-Purkinje Cell Synapses in Two Friedreich's Ataxia Mouse Models. Cerebellum. 2025 Feb 5;24(2):42. doi: 10.1007/s12311-025-01796-0. PMID: 39907933; PMCID: PMC11799031.

To investigate the neural circuit basis of this dysfunction, we employed field recordings to measure Purkinje cell (PC) function and synaptic properties along with western blotting and immunohistochemistry to determine their density and structure in two established FRDA mouse models, the shRNA-frataxin (FRDAkd) and the frataxin knock in-knockout (KIKO) mice. Western blotting demonstrated subtle changes in mitochondrial proteins and only a modest reduction in the density of calbindin positive cells PCs in the cerebellar cortex of the FRDAkd mice, with no change in the density of PCs in the KIKO mice. Though PC density differed slightly in the two models, field recordings of parallel fiber-PC synapses in the molecular layer demonstrated concordant hypo-excitability of basal synaptic transmission and impairments of long-term plasticity using induction protocols associated with both potentiation and depression of synaptic strength. These results indicate that synaptic instability might be a common feature in FRDA mouse models.

Heart Gene Therapy Astellas Withdrawing

Astellas Pharma Inc., February 4, 2025Q3 YTD/FY2024 Financial Results (pg 13 and 33)

Pandolfo M. Friedreich Ataxia: An (Almost) 30-Year History After Gene Discovery

Pandolfo M. Friedreich Ataxia: An (Almost) 30-Year History After Gene Discovery. Neurol Genet. 2025 Jan 13;11(1):e200236. doi: 10.1212/NXG.0000000000200236. PMID: 39810753; PMCID: PMC11731367. 

 Now, 28 years after the gene discovery, although much remains to be understood about the disease's mechanisms and the development of effective therapies, the progress is undeniable. A thriving community has emerged, uniting researchers, health care providers, industry professionals, individuals with FRDA, their families, and dedicated volunteers. With this collective effort, a cure is within reach.

Identification of strengths and weaknesses of the healthcare system for persons living with rare diseases in Catalonia (Spain), and recommendations to improve its comprehensive attention: the “acERca las enfermedades raras” project

Hernández-Rodríguez, J., Martínez-Valle, F., Acebes, X. et al. Identification of strengths and weaknesses of the healthcare system for persons living with rare diseases in Catalonia (Spain), and recommendations to improve its comprehensive attention: the “acERca las enfermedades raras” project. Orphanet J Rare Dis 20, 42 (2025). Doi:10.1186/s13023-024-03518-x 

 Based on the criteria of equity and equality for which a public healthcare must be guaranteed to all citizens, PLWRD have also the right to access to all the available resources in a way that is as agile and equal as for other patients. The expert participants considered that the current Catalan healthcare model for RDs consists of a pioneer and advanced plan, unique in Spain, consisting of a functional network of qualified reference centers (XUECs), following the European model of the ERN thematic areas.

Unraveling Mechanisms and Potential Treatment of Cardiomyopathy in Friedreich’s Ataxia

Published on January 30, 2025 in Cornerstone Blog. Studying both patient-derived cardiac cells and zebrafish models will help Drs. Wilson and Pei to identify potential inflammatory signaling that may exacerbate FA.

Jupiter Neurosciences partners with Zina for Parkinson's trial

Jupiter, Florida, Jan. 30, 2025 (GLOBE NEWSWIRE) -- Jupiter Neurosciences, Inc. (NASDAQ: JUNS) (“Jupiter” or the “Company”), a clinical-stage pharmaceutical company developing JOTROL™, a patented resveratrol-based platform, today announced a strategic partnership with Zina Biopharmaceuticals, LLC ("Zina") to support all aspects of Jupiter’s upcoming Phase 2a clinical trial for Parkinson’s disease. 

 Jupiter Neurosciences (JUNS) conducted a Phase I study demonstrating that JOTROL achieves over nine times higher bioavailability compared to resveratrol used in earlier clinical trials (e.g., Turner et al., MCI/Early Alzheimer’s Disease trial, and Yui et al., Friedreich’s Ataxia trial). The results of this Phase I study, which will be cross-referenced in all upcoming JOTROL trials, were published in the Journal of Alzheimer’s Disease and AAPS Open in February 2022.

'Editorial: The Mechanistic Investigation and Emerging Therapies for Friedreich's Ataxia'

Yina Dong, Vijayendran Chandran, Elisabetta Soragni, David R Lynch, Front. Pharmacol. Sec. Neuropharmacology Volume 16 - 2025 doi:10.3389/fphar.2025.1560808

By integrating mechanistic insights with novel therapeutic approaches and outcome measures, this collection paves the way for more comprehensive and effective interventions for FRDA patients.

Larimar Therapeutics Announces Dosing of Adolescents in Nomlabofusp Pediatric Pharmacokinetic Run-In Study for Patients with Friedreich’s Ataxia

BALA CYNWYD, Pa., Jan. 23, 2025 (GLOBE NEWSWIRE) -- Larimar Therapeutics, Inc. (Larimar) (Nasdaq: LRMR), today announced that dosing of adolescents 12-17 years old has started in the Company’s pediatric PK run-in study for patients with Friedreich’s ataxia (FA). 

 “Dosing adolescents is the first step in evaluating the safety and PK of nomlabofusp in pediatric patients with FA. We continue to enroll adolescents in our first cohort. This cohort will be followed by a second cohort of children 2-11 years old. We expect to transition both the adolescents and children into the ongoing OLE study after assessing safety and exposure data from each successive cohort,” said Dr. Rusty Clayton, Chief Medical Officer of Larimar. “We look forward to reporting long-term 50 mg data in adults from our OLE study, as well as available data from adolescents completing the pediatric PK run-in study, in mid- 2025.”

Hypoxia as a medicine

Robert S. Rogers, Vamsi K. Mootha. Hypoxia as a medicine. Science Translational Medicine 22 Jan 2025 Vol 17, Issue 782 DOI: 10.1126/scitranslmed.adr4049

Oxygen is essential for human life, yet a growing body of preclinical research is demonstrating that chronic continuous hypoxia can be beneficial in models of mitochondrial disease, autoimmunity, ischemia, and aging. This research is revealing exciting new and unexpected facets of oxygen biology, but translating these findings to patients poses major challenges, because hypoxia can be dangerous.

Solid Biosciences Receives FDA Fast Track Designation for SGT-212 Dual Route of Administration Gene Therapy for Friedreich’s Ataxia

CHARLESTOWN, Mass., Jan. 21, 2025 (GLOBE NEWSWIRE) -- Solid Biosciences Inc. today announced that it has received Fast Track designation from the U.S. Food and Drug Administration (FDA) for SGT-212, the Company’s, AAV-based gene therapy candidate for the treatment of Friedreich’s ataxia (FA). SGT-212 will deliver the full-length frataxin gene via dual routes of administration incorporating intradentate nucleus (IDN) and intravenous (IV) infusions, designed to promote restoration of therapeutic levels of the frataxin protein to address neurologic, cardiac and systemic clinical manifestations of FA.

Friedreich ataxia: what can we learn from non-GAA repeat mutations?

Lynch DR, Shen M, Wilson RB. Friedreich ataxia: what can we learn from non-GAA repeat mutations? Neurodegener Dis Manag. 2025 Jan 15:1-10. doi: 10.1080/17582024.2025.2452147. Epub ahead of print. PMID: 39810561. 

 Compound heterozygote patients with one expanded GAA allele and a non-GAA repeat mutation can have subtle differences in phenotype from typical FRDA, including, in patients with selected missense mutations, both more severe features and less severe features in the same patient. In this review, we propose explanations for such phenotypes based on the potential for activities of frataxin other than enhancement of iron-sulfur cluster synthesis, as well as crucial future experiments for fully understanding the role of frataxin in cells.

Altered Intracerebellar Functional Connectivity in Friedreich's Ataxia: A Graph-Theory Functional MRI Study

Tranfa M, Costabile T, Pontillo G, Scaravilli A, Pane C, Brunetti A, Saccà F, Cocozza S. Altered Intracerebellar Functional Connectivity in Friedreich's Ataxia: A Graph-Theory Functional MRI Study. Cerebellum. 2025 Jan 14;24(2):30. doi: 10.1007/s12311-025-01785-3. PMID: 39808241; PMCID: PMC11732920. 

Graph analysis revealed regional intra-cerebellar FC changes in FRDA, marked by reduced functional centrality in cerebellar regions of the vermis and responsible for executive functions. These changes correlated with cognitive alterations, highlighting the role of the cerebellar cortex in the cognitive impairment observed in FRDA. In conclusion, our observations confirm that the cerebellum is involved in the pathophysiology of FRDA not only from a structural, but also from a functional standpoint, and suggests that integrating information from different parcellations could provide complementary knowledge and help us in decoding the exact relationship between FC alterations and cognitive changes in FRDA.

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. 

 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.

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.

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.

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.

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.

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.