A wearable motion capture suit and machine learning predict disease progression in Friedreich’s ataxia

Balasundaram Kadirvelu, Constantinos Gavriel, Sathiji Nageshwaran, Jackson Ping Kei Chan, Suran Nethisinghe, Stavros Athanasopoulos, Valeria Ricotti, Thomas Voit, Paola Giunti, Richard Festenstein & A. Aldo Faisal; Nat Med (2023). doi:10.1038/s41591-022-02159-6

Our work demonstrates how data-derived wearable biomarkers can track personal disease trajectories and indicates the potential of such biomarkers for substantially reducing the duration or size of clinical trials testing disease-modifying therapies and for enabling behavioral transcriptomics.

Proprioceptors-enriched neuronal cultures from induced pluripotent stem cells from Friedreich ataxia patients show altered transcriptomic and proteomic profiles, abnormal neurite extension, and impaired electrophysiological properties

Chiara Dionisi, Marine Chazalon, Myriam Rai, Céline Keime, Virginie Imbault, David Communi, Hélène Puccio, Serge N Schiffmann, Massimo Pandolfo; Brain Communications, 2023;, fcad007, doi:10.1093/braincomms/fcad007 

 Our study suggests the existence of abnormalities affecting proprioceptors in Friedreich ataxia, particularly their ability to extend towards their targets and transmit proper synaptic signals. It also highlights the need for further investigations to better understand the mechanistic link between FXN silencing and proprioceptive degeneration in Friedreich ataxia.

Form S-1/A JUPITER NEUROSCIENCES

As filed with the U.S. Securities and Exchange Commission on January 17, 2023. 

JOTROL™ is a micellar non-aqueous solution of resveratrol delivered in a softgel capsule. Each capsule includes 100mg of resveratrol. Pre-clinical trials in mice and rats were conducted comparing JOTROL™ to micronized resveratrol, labeled to have the highest bioavailability in the nutritional market, to demonstrate that we could achieve a significantly higher bioavailability.

Neurobehavioral deficits of mice expressing a low level of G127V mutant frataxin

Daniel Fil, Robbie L. Conley, Aamir R. Zuberi, Cathleen M. Lutz, Terry Gemelli, Marek Napierala, Jill S. Napierala; Neurobiology of Disease, Volume 177, 2023, 105996, ISSN 0969-9961, doi:10.1016/j.nbd.2023.105996. 

 Results of these studies provide insight into the unique pathogenic mechanism of the FXN G130V mechanism and the tolerable limit of Fxn/FXN expression in vivo.

Quantitative Oculomotor Assessment in Hereditary Ataxia: Discriminatory Power, Correlation with Severity Measures, and Recommended Parameters for Specific Genotypes

Pilar Garces, Chrystalina A. Antoniades, Anna Sobanska, Norbert Kovacs, Sarah H. Ying, Anoopum S. Gupta, Susan Perlman, David J. Szmulewicz, Chiara Pane, Andrea H. Németh, Laura B. Jardim, Giulia Coarelli, Michaela Dankova, Andreas Traschütz & Alexander A. Tarnutzer; Cerebellum (2023). doi:10.1007/s12311-023-01514-8 

Recommendation of other paradigms was limited by the scarcity of cross-validating correlations, except saccadic intrusions (FRDA), pursuit eye movements (SCA17), and quantitative head-impulse testing (SCA3/6). This work aids in understanding the current knowledge of quantitative oculomotor parameters in hereditary ataxias, and identifies gaps for validation as potential trial outcome measures in specific ataxia genotypes.

Ketolysis is Required for the Proper Development and Function of the Somatosensory Nervous System

Jonathan Enders, Jarrid Jack, Sarah Thomas, Paige Lynch, Sarah Lasnier, Xin Cao, M Taylor Swanson, Janelle M Ryals, John P Thyfault, Patrycja Puchalska, Peter A Crawford, Douglas E Wright; bioRxiv 2023.01.11.523492; doi:10.1101/2023.01.11.523492 

We conclude that ketone metabolism is essential for the development of the somatosensory nervous system. These findings also suggest that decreased ketone oxidation in the somatosensory nervous system may explain the neurological symptoms of Friedreich's ataxia.

FXN gene methylation determines carrier status in Friedreich ataxia

Lam C, Gilliam KM, Rodden LN, Schadt KA, Lynch DR, Bidichandani S.; J Med Genet. 2023 Jan 12:jmedgenet-2022-108742. doi: 10.1136/jmg-2022-108742. Epub ahead of print. PMID: 36635061. 

 FXN DNA methylation reliably detects the GAA-TRE in the heterozygous state and offers a robust alternative strategy to diagnose FRDA due to compound heterozygosity and to identify asymptomatic heterozygous carriers of the GAA-TRE.

Prime Medicine (PRME) Announces Recent Progress and Highlights 2023 Strategic Priorities

January 9, 2023; “Today, we are pleased to announce accomplishments across our portfolio and platform, including new preclinical proof-of-concept data in Friedrich’s ataxia and cystic fibrosis showing restoration of genetic function.

In preclinical studies, Prime Medicine is using its technology to precisely remove the GAA pathological repeats at the FXN gene, restoring Frataxin protein expression and sensory neuron function in patient dorsal root ganglia. Today, Prime Medicine announced new preclinical data demonstrating that Prime Editing-mediated removal of pathological repeats in vitro results in correction of hypermethylation at the FXN gene, restoring genetic function back to wild-type levels. The company believes these data also support the evaluation of Prime Editing for the potential treatment of other repeat expansion diseases, many of which exhibit hypermethylation as a key feature of the underlying pathogenesis.

S-Glutathionylation and S-Nitrosylation in Mitochondria: Focus on Homeostasis and Neurodegenerative Diseases

Vrettou S, Wirth B.; International Journal of Molecular Sciences. 2022 Dec;23(24):15849. DOI: 10.3390/ijms232415849. PMID: 36555492; PMCID: PMC9779533. 

We discuss how S-glutathionylation and S-nitrosylation interfere in mitochondrial homeostasis and how the deregulation of these modifications is associated with Alzheimer's, Parkinson's, amyotrophic lateral sclerosis and Friedreich's ataxia.

ODs with a positive TPR conclusion, not subject to a conditional approval, and approved without requering a pass would be more likely to be reimbursed in Spain

José Luis Poveda, Claudia Gómez, Alicia Gil & Xavier Badia; Orphanet J Rare Dis 18, 4 (2023). doi:10.1186/s13023-022-02610-4 

This study shows that the TPR plays a key role in the P&R process in Spain and highlights that traditional evaluation tools, such us safety and efficacy, were the main drivers of P&R decisions for ODs. A positive conclusion of the TPR, non-conditional approval by the EMA and no obligation for a PASS seems to favourably affect P&R decisions in Spain.