Cracking the code: a head-to-head comparison of expert clinicians and artificial intelligence in diagnosing rare diseases

Sendtner, G.W., Muecke, M., Grigull, L. et al. Cracking the code: a head-to-head comparison of expert clinicians and artificial intelligence in diagnosing rare diseases. Orphanet J Rare Dis 20, 564 (2025). doi:10.1186/s13023-025-04112-5

In this study, we showed that the differential diagnostic tool “Isabel Healthcare” can assist in identifying patient diagnoses. However, discrepancies between the tool’s output and the interdisciplinary case conferences were observed, indicating that while “Isabel Healthcare” can aid clinicians when filtered input is applied, it may not yet be fully effective on its own. Our findings highlight the potential of tools like “Isabel Healthcare” in the diagnostic process but emphasize the essential role of clinicians in filtering and contextualizing medical information.

Deep learning-based 3D reconstruction of dentate nuclei in Friedreich’s ataxia from T2*weighted MR images

Trushal Sardhara, Ravi Dadsena, Roland C. Aydin, Ralf-Dieter Hilgers, Leon Horn, Jörg B. Schulz, Kathrin Reetz, Sandro Romanzetti, Imis Dogan, Stella A. Lischewski, Kerstin Konrad, Miguel Pishnamaz, Maximillian Praster, Thomas Clavel, Vera Jankowski, Joachim Jankowski, Oliver Pabst, Katharina Marx-Schütt, Nikolaus Marx, Julia Möllmann, Malte Jacobsen, Juergen Dukart, Simon Eickhoff, Deep learning-based 3D reconstruction of dentate nuclei in Friedreich’s ataxia from T2*weighted MR images, Machine Learning with Applications, 2025, 100790, ISSN 2666-8270, doi:10.1016/j.mlwa.2025.100790. 

 We present a transfer learning–based machine learning pipeline for automated DN segmentation that directly uses standard T2*-weighted Magnetic Resonance Imaging (MRI), which highlights the DN without additional processing, and is designed to perform robustly with limited annotated data.

Voyager Reports Third Quarter 2025 Financial and Operating Results

LEXINGTON, Mass., Nov. 10, 2025 (GLOBE NEWSWIRE) -- Voyager Therapeutics, Inc. (Nasdaq: VYGR), a biotechnology company dedicated to leveraging genetics to treat neurological diseases, today reported third quarter 2025 financial and operating results.

Neurocrine partnership update: Neurocrine has indicated that they expect to provide an update on the IND filing timelines for their Friedreich’s ataxia (FA) and GBA1 gene therapy programs by the end of 2025. These filings could enable the initiation of clinical trials in 2026, pending supportive outcomes from the ongoing GLP toxicology studies, acceptance of the INDs by the FDA, and Neurocrine’s internal strategic assessment. Additionally, Neurocrine initiated a preclinical toxicology study with the fourth development candidate in a gene therapy program partnered with Voyager, triggering a $3 million milestone payment that is owed to Voyager in the fourth quarter of 2025.

Larimar Therapeutics, Inc. Updates on Nomlabofusp Development

On November 10, 2025, Larimar Therapeutics, Inc. provided updates on its nomlabofusp clinical program and future plans.

Individualized exercise and NAD+ precursor supplementation in Friedreich’s Ataxia: a randomized controlled trial

Lin, Kimberly Y. and Lin, Kimberly Y. and Bucha, Anna and Bucha, Anna and McSweeney, Kara and McSweeney, Kara and Wade, Kristin L. and Wade, Kristin L. and Karaj, Antoneta and Tamaroff, Jaclyn and Tamaroff, Jaclyn and O'Malley, Shannon and O'Malley, Shannon and Chung, Nicole M. and Chung, Nicole M. and Cilenti, Nicolette A. and Cilenti, Nicolette A. and Wanner, Julianne and Wanner, Julianne and Adzika, Gabriel K. and Adzika, Gabriel K. and Mesaros, Clementina and Blair, Ian A. and Blair, Ian A. and Rojsajjakul, Teerapat and Rojsajjakul, Teerapat and Serai, Suraj and Serai, Suraj and Farmer, Jennifer and Farmer, Jennifer and Bryant, Kyle and Bryant, Kyle and Lu, Yingying and Lu, Yingying and Harhay, Michael and Harhay, Michael and Weber, David R. and Weber, David R. and Paridon, Stephen M. and Paridon, Stephen M. and Seifert, Erin and Putt, Mary E. and Zamani, Payman and Zamani, Payman and Baur, Joseph A. and Lynch, David R. and Lynch, David R. and McCormack, Shana E. and McCormack, Shana E., Individualized exercise and NAD+ precursor supplementation in Friedreich’s Ataxia: a randomized controlled trial. doi:10.2139/ssrn.5698224. 

Interpretation: NR plus exercise for 12 weeks was safe and increased cardiovascular fitness in children and adults with FRDA. Adding NR to exercise could be considered as part of a comprehensive treatment approach.

The Triple Flexion Response in Friedrich’s Ataxia

Saluja A, Sahib A, Yadav V (November 04, 2025) The Triple Flexion Response in Friedrich’s Ataxia. Cureus 17(11): e96080. doi:10.7759/cureus.96080 

The triple flexion response is a significant diagnostic clue highlighting the marked corticospinal tract involvement in advanced Friedrich's ataxia.

Solid Biosciences Reports Third Quarter 2025 Financial Results

CHARLESTOWN, MA, Nov. 03, 2025 FA

(SGT-212): Solid has activated the first clinical trial site and is currently screening participants for FALCON, a Phase 1b first-in-human clinical trial evaluating SGT-212 for the treatment of Friedreich’s ataxia. 

SGT-212 for Friedreich’s Ataxia (FA)

In October 2025, the Company activated the first clinical trial site and began participant screening for FALCON, a first-in-human, open-label, Phase 1b clinical trial of SGT-212. The trial is expected to enroll non-ambulatory and ambulatory adult participants living with FA in up to three cohorts and is designed to evaluate the safety and tolerability of systemic and bilateral intradentate nucleus (IDN) administration of SGT-212. SGT-212 is the first investigational gene therapy for FA to utilize a dual route of administration and is intended to promote restoration of therapeutic levels of the frataxin protein to address the neurologic, cardiac and systemic clinical manifestations of FA.

Solid Biosciences Reports Third Quarter 2025 Financial Results

Early experience on omaveloxolone in adult patients with Friedreich's ataxia: a real-world observational study

Lima SM, Caltagirone M, Messina C, Quartetti U, Rini N, D'Amico F, Brighina F, Di Stefano V. Early experience on omaveloxolone in adult patients with Friedreich's ataxia: a real-world observational study. J Neurol. 2025 Nov 1;272(11):742. doi: 10.1007/s00415-025-13487-1. PMID: 41176519. 

 Omaveloxolone seems to be safe and well-tolerated in adult FRDA patients in the real-life setting. No significant worsening of symptoms was observed with no signs of progression, as well as the improvement of inflammatory biomarkers after 24 weeks of treatment, but no predictive factors for the disease response have been identified. However, the short duration, and the small sample size limit the generalizability of the results. Further studies with longer observation are needed to clearly define the efficacy of omaveloxolone in FRDA.

Friedreich ataxia:

Subramony SH, Lynch DR. Friedreich Ataxia. Pediatr Neurol. 2025 Nov 1;174:148-154. doi: 10.1016/j.pediatrneurol.2025.10.020. Epub ahead of print. PMID: 41252802.

With the introduction of potential new therapy for Friedreich ataxia (FRDA), the disorder has taken on a new importance in the world of pediatric neurology. Originally described more than 150 years ago, large scale clinical studies have defined diagnostic criteria and the underlying mutation as a biallelic, unstable expansion of an intronic GAA repeat in chromosome 9. In this review, we summarize the clinical features, routine management, pathophysiology, and emerging therapies for this devastating disease. The recent approval of omaveloxolone makes recognition of FRDA and its treatment essential for all pediatric neurologists.

Drivers of managed entry agreements to reduce reimbursement challenges of orphan medicinal products: the development of a matrix

Callenbach, M.H.E., van den Berg, S., Hulsbosch, A. et al. Drivers of managed entry agreements to reduce reimbursement challenges of orphan medicinal products: the development of a matrix. Orphanet J Rare Dis 20, 540 (2025). doi:10.1186/s13023-025-04020-8 

"New orphan medicinal products (OMPs) are increasingly expensive and approved with limited clinical evidence". 

The matrix provides a systematic approach applied to mitigate clinical and cost-effectiveness uncertainties and/or reimbursement challenges specific to OMPs through advising MEAs. This study highlights the diversity in the drivers of MEAs to reduce risk and reimbursement challenges specific to OMPs and underscores the relevance of considering both established and innovative MEAs to address these.