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.

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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!

Jupiter Orphan Therapeutics Announces First Patient Dosed in Phase I Dose Escalation Study of JOTROL™

JUPITER, Fla., Jan. 11, 2021 /PRNewswire/ -- Jupiter Orphan Therapeutics, Inc. ("JOT") a biotechnology company pioneering a novel and disease modifying product named JOTROL™, today announced that the first patient has been dosed in a Phase I dose escalation study of JOTROL™. The Phase I is conducted with healthy volunteers in various ages and include a food effect arm. Per protocol, the first patient cohort has been dosed and the study is continuing in January and February of 2021. Top line data is expected to be available in March 2021. The initial dose appear well-tolerated as the escalation continues toward clinically relevant doses. JOTROL™ is, through its unique bioavailability, the first and only resveratrol product that can deliver a therapeutically effective dose without causing any severe gastro-intestinal side effects. JOTROL™ is a platform product that is expected to be an effective treatment in many rare diseases such as ataxias, lysosomal storage disorders and mitochondrial diseases. 

 We are assuming positive Phase I results, which will be a Proof Of Concept of our product and have started preparations for Phase II trials in MPS-1, Friedreich's ataxia and MELAS in addition to MCI study preparation. We have presently cash covering us through 2021 and are targeting additional financing through an equity raise, possible partnering as well as utilizing non-dilutive funding sources to be able to start several Phase II trials later in 2021," stated Christer Rosén, Chairman and CEO.

Cytoprotective activities of kinetin purine isosteres

Barbara Maková, Václav Mik, Barbora Lišková, Gabriel González, Dominik Vítek, Martina Medvedíková, Beata Monfort, Veronika Ručilová, Alena Kadlecová, Prashant Khirsariya, Zoila Gándara Barreiro, Libor Havlíček, Marek Zatloukal, Miroslav Soural, Kamil Paruch, Benoit D'Autréaux, Marián Hajdúch, Miroslav Strnad, Jiří Voller, Bioorganic & Medicinal Chemistry, 2021, 115993, doi:10.1016/j.bmc.2021.115993. 

 Our findings indicate that kinetin isosteres protect Friedreich́s ataxia patient-derived fibroblasts against glutathione depletion, protect neuron-like SH-SY5Y cells from glutamate-induced oxidative damage, and correct aberrant splicing of the ELP1 gene in fibroblasts derived from a familial dysautonomia patient. Although the mechanism of action of kinetin derivatives remains unclear, our data suggest that the cytoprotective activity of some purine isosteres is mediated by their ability to reduce oxidative stress. Further, the studies of permeation across artificial membrane and model gut and blood-brain barriers indicate that the compounds are orally available and can reach central nervous system. Overall, our data demonstrate that isosteric replacement of the kinetin purine scaffold is a fruitful strategy for improving known biological activities of kinetin and discovering novel therapeutic opportunities.