Ectopic Burden Via Holter Monitors in Friedreich’s Ataxia,

Erika Mejia, Abigail Lynch, Patrick Hearle, Oluwatimilehin Okunowo, Heather Griffis, Maully Shah, David Lynch, Kimberly Y. Lin; Pediatric Neurology, 2021, doi:10.1016/j.pediatrneurol.2021.01.004. 

Patients with longer disease duration had higher rates of SVE. Heart rhythm monitoring may be considered for risk stratification, however longitudinal analysis is needed.

AVXS-401, by Novartis Gene Therapies

25/01/2021. AVXS-401 is a gene therapy developed by Novartis Gene Therapies (AveXis, now is part of Novartis). It uses the AAV9 adeno-associated virus (AAV) vector to deliver a functional copy of the FXN gene to restore the production of frataxin in tissues that are severely affected by FA. Early toxicity studies conducted in healthy mice showed that AVXS-401 has good safety and tolerability. Efficacy studies have shown that in a FA mouse model lacking frataxin in the central nervous system, a single intracerebroventricular (ICV) injection of low-dose AVXS-401 can improve behavior and promote glial cell proliferation. In a mouse model lacking frataxin in the heart, AVXS-401 can restore heart function, prolong the median survival by more than 3 times, and prevent the onset of cardiovascular disease. When the therapeutic dose is increased proportionally and administered in non-human primates, AVXS-401 can achieve sustained expression of frataxin in the central nervous system and heart, and the effect is still obvious after 6 months of treatment.

Novartis Gene Therapies gets FDA Orphan Drug Designation in Friedreich's Ataxia

01/21/2021. Novartis Gene Therapies gets FDA Orphan Drug Designation in Friedreich's Ataxia, Novartis Gene Therapies announced that the U.S. Food and Drug Administration has granted Orphan Drug Designation for its "Adeno-associated virus isoform 9 gene vector construct expressing the human Frataxin gene" for the treatment of Friedreich's Ataxia.

-

Generic Name:	Adeno-associated virus isoform 9 gene vector construct expressing the human Frataxin gene
Date Designated:	01/21/2021
Orphan Designation:	Treatment of Friedreich`s Ataxia.
Orphan Designation Status:	Designated
FDA Orphan Approval Status:	Not FDA Approved for Orphan Indication
Sponsor:	Novartis Gene Therapies 2275 Half Day Road, Suite 300 Bannockburn, Illinois 60015 United States The sponsor address listed is the last reported by the sponsor to OOPD.

*Exclusivity Protected Indications are shown for approvals from Jan. 1, 2013, to the present.

Supportive care needs of patients with rare chronic diseases: multi-method, cross-sectional study

Miram K. Depping, Natalie Uhlenbusch, Yskert von Kodolitsch, Hans F. E. Klose, Victor-Felix Mautner & Bernd Löwe; Orphanet J Rare Dis 16, 44 (2021). doi:10.1186/s13023-020-01660-w 

Patients affected by rare diseases have high unmet support needs in all areas studied. Multidisciplinary care, including psychological support and the provision of information regarding the healthcare system, treatment options, disease course and sexuality, might help address these needs.

PGC‐1α protects from myocardial ischaemia‐reperfusion injury by regulating mitonuclear communication

Li, Y‐Q, Jiao, Y, Liu, Y‐N, Fu, J‐Y, Sun, L‐K, Su, J.; J Cell Mol Med. 2021; 00: 1‐ 8. doi:10.1111/jcmm.16236 In this review, we speculate the role of PGC‐1α as a key regulator of mitonuclear communication, which may interacts with nuclear factor, erythroid 2 like ‐1 and ‐2 (NRF‐1/2) to inhibit mitochondrial oxidative stress, promote the clearance of damaged mitochondria, enhance mitochondrial biogenesis, and reduce the burden of IRI.

Efficacy of echocardiography for differential diagnosis of left ventricular hypertrophy: special focus on speckle-tracking longitudinal strain

Tanaka, H.; J Echocardiogr (2021). doi:10.1007/s12574-020-00508-3 

The underlying mechanisms of myocardial dysfunction in patients with Friedreich’s ataxia might be associated with myocyte cellular hypertrophy, iron deposits, focal necrosis, and diffuse fibrosis.

Methylated and unmethylated epialleles support variegated epigenetic silencing in Friedreich ataxia

Layne N Rodden, Yogesh K Chutake, Kaitlyn Gilliam, Christina Lam, Elisabetta Soragni, Lauren Hauser, Matthew Gilliam, Graham Wiley, Michael P Anderson, Joel M Gottesfeld, David R Lynch, Sanjay I Bidichandani, Human Molecular Genetics, ddaa267, doi:10.1093/hmg/ddaa267

The higher prevalence in mild FRDA of somatic FXN epialleles devoid of DNA methylation is consistent with variegated epigenetic silencing mediated by expanded triplet-repeats. The proportion of unsilenced somatic FXN genes is an unrecognized phenotypic determinant in FRDA, and has implications for the deployment of effective therapies.

Omaveloxolone: potential new agent for Friedreich ataxia

David R Lynch and Joseph Johnson; Future Medicine, Neurodegenerative Disease Management 0 0:0 Published Online:12 Jan 2021 doi:10.2217/nmt-2020-0057

In this work, we review the evidence for use of omaveloxolone in FRDA from recent clinical trials. Though not at present approved for any indication, the present data suggest that this agent acting though increases in Nrf2 activity may provide a novel therapy for FRDA.

Dimethyl fumarate dose-dependently increases mitochondrial gene expression and function in muscle and brain of Friedreich’s ataxia model mice

Chun Kiu Hui, Elena N Dedkova, Claire Montgomery, Gino Cortopassi, Human Molecular Genetics, , ddaa282, doi:10.1093/hmg/ddaa282 

We observed significant decreases of multiple mitochondrial parameters, including deficits in brain mitochondrial Complex 2, Complex 4, and aconitase activity, supporting the idea that frataxin deficiency reduces mitochondrial gene expression, mitochondrial functions and biogenesis. 110 mg/kg oral DMF rescued these enzyme activities in brain and rescued frataxin and cytochrome oxidase expression in brain, cerebellum and quadriceps muscle of the FXNKD mouse model. Taken together, these results support the idea of using fumarate-based molecules to treat Friedreich’s ataxia or other mitochondrial diseases.

NAF Supports FARA’s Call to Action

January 15, 2021; Friedreich’s Ataxia Research Alliance (FARA) is encouraging Reata Pharmaceuticals to submit a New Drug Application (NDA) for Omaveloxolone, which recently completed a Phase III clinical trial as a treatment for Friedreich’s Ataxia (FA). FARA is also urging the Food and Drug Administration (FDA) to consider approving the NDA. FARA has prepared a letter that will be submitted to Reata Pharmaceuticals and the FDA; they are looking for supporters to sign the letter. NAF submitted a letter of support. To date, FARA has received more than 40,000 signatures from patients, their family and friends, and rare disease advocates. We want you to sign on too!