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FARAFARA Cure FA

 

Scientific News

FARA funds research progress

In this section, you will find the most recent FA research publications, many of which are funded by FARA, as well as information on upcoming conferences and symposiums. You can search for articles by date using the archive box in the right hand column. To locate FARA Funded or Supported Research, click the hyperlink in the right hand column. You may also search for specific content using key words or phrases in the search button at the top right of your screen. Please be sure to visit other key research sections of our website for information on FARA’s Grant Program and the Treatment Pipeline.

 


 

Cerebral Abnormalities in Friedreich Ataxia: A Review

Friedreich ataxia (FRDA) is an inherited degenerative disorder affecting multiple systems of the body and resulting in symptoms which include progressive ataxia, dysarthria, and cardiomyopathy. Central nervous system pathology has been traditionally ascribed to the spinal cord and dentate nucleus of the cerebellum. However, cerebral abnormalities in FRDA are being increasingly documented via multiple neuroimaging techniques. Understanding the nature and implications of cerebral abnormalities in FRDA provides more comprehensive knowledge of nervous system involvement in this disorder and increases the prospects of identifying effective treatment targets. We review the cerebellar and the cerebral involvement with a focus on the emerging in vivo human neuroimaging findings suggesting wide-spread cerebral involvement, including aberrant cerebellar-cerebral connectivity. We synthesise the findings by proposing potential mechanisms that may drive these effects. Finally, we identify future research directions which, we argue, will lead to a better understanding of the extent and potential mechanisms of cerebral aberrations in FRDA.

Read more HERE

Jupiter Orphan Therapeutics Receives Orphan Drug Designation for its Trans-Resveratrol Product JOTROL for Treatment of Friedreich's Ataxia

Jupiter Orphan Therapeutics, Inc. ("JOT"), Jupiter, FL, today announced that it has received notification from the US Food and Drug Administration (FDA) that its Orphan Drug Designation request for trans-Resveratrol has been granted.

"Orphan Drug Designation serves as an important milestone for JOT as it positions our JOTROL™ product as a potential treatment for FA. We are hopeful that JOTROL™ can ultimately provide a meaningful treatment for FA patients around the world based on the earlier Phase II trial, utilizing resveratrol, conducted by our partner Murdoch Children's Research Institute, Melbourne, Australia ("MCRI"). That trial was an open label trial and generated very encouraging results, where 4 out of 5 very important endpoints were met. We, JOT together with MCRI, expect to repeat these results through a larger placebo controlled study utilizing JOTROL™ to avoid the Gastro Intestinal (GI) tolerability issues. This will hopefully lead to market approval in several territories, including USA" said Chief Executive Officer, Christer Rosén of JOT.

Read more HERE

Selected missense mutations impair frataxin processing in Friedreich ataxia

Frataxin (FXN) is a highly conserved mitochondrial protein. Reduced FXN levels cause Friedreich ataxia, a recessive neurodegenerative disease. Typical patients carry GAA repeat expansions on both alleles, while a subgroup of patients carry a missense mutation on one allele and a GAA repeat expansion on the other. This article reports that selected disease-related FXN missense mutations impair FXN localization, interaction with mitochondria processing peptidase, and processing.

The group found that FXNI154F and FXNG130V missense mutations decrease FXN 81-210 levels compared with FXNWT, FXNR165C, and FXNW155R, but do not block its association with mitochondria. FXNI154F and FXNG130V also impair FXN maturation and enhance the binding between FXN 42-210 and mitochondria processing peptidase. Furthermore, blocking proteosomal degradation does not increase FXN 81-210 levels. Additionally, impaired FXN processing also occurs in fibroblasts from patients with FXNG130V. Finally, clinical data from patients with FXNG130V and FXNI154F mutations demonstrates a lower severity compared with other individuals with Friedreich ataxia.

These data suggest that the effects on processing associated with FXNG130V and FXNI154F mutations lead to higher levels of partially processed FXN, which may contribute to the milder clinical phenotypes in these patients.

Read more HERE

FDA Confirms That Use of mFARS as Primary Endpoint in Part 2 of the MOXIe Trial Can Support Approval of Omaveloxolone in Friedreich’s Ataxia

Reata Pharmaceuticals, a clinical-stage biopharmaceutical company, today announced that the U.S. Food and Drug Administration (FDA) confirmed that the modified Friedreich’s Ataxia Rating Scale (mFARS) is an acceptable primary endpoint for Part 2 of the MOXIe trial for omaveloxolone in Friedreich’s ataxia (FA).

The FDA communication was made in response to the Company’s request that the FDA confirm its prior guidance that, depending on the MOXIe trial results, mFARS could be appropriate to support approval of omaveloxolone for FA under Subpart H. In the recent communication, FDA indicated that it may consider either accelerated or full approval based on the overall results of the trial and strength of the data. FDA also recommended that the Company extend the treatment duration for Part 2 of the study and add a straightforward patient-reported or performance-based outcome endpoint to the study.

Read more HERE

Heart and Nervous System Pathology in Compound Heterozygous Friedreich Ataxia

In a small percentage of patients with Friedreich ataxia (FA), the pathogenic mutation is compound heterozygous, consisting of a guanine-adenine-adenine (GAA) trinucleotide repeat expansion in one allele, and a deletion, point mutation, or insertion in the other. In 2 cases of compound heterozygous FA, the GAA expansion was inherited from the mother, and deletions from the father. Compound heterozygous FA patient 1, an 11-year-old boy (GAA, 896/c.11_12TCdel), had ataxia, chorea, cardiomyopathy, and diabetes mellitus. Compound heterozygous FA patient 2, a 28-year-old man (GAA, 744/exon 5 del), had ataxia, cardiomyopathy, and diabetes mellitus. Microscopy showed cardiomyocyte hypertrophy, iron-positive inclusions, and disrupted intercalated discs. The cardiac lesions were similar to those in age-matched homozygous FA patients with cardiomyopathy and diabetes mellitus (boy, 10, GAA 1016/1016; woman, 25, GAA 800/1100). The neuropathology was also similar and included hypoplasia of spinal cord and dorsal root ganglia, loss of large axons in dorsal roots, and atrophy of the dentate nucleus (DN). Frataxin levels in heart and DN of all 4 FA cases were at or below the detection limits of the enzyme-linked immunosorbent assay (≤10 ng/g wet weight) (normal DN: 126 ± 43 ng/g; normal heart: 266 ± 92 ng/g). The pathologic phenotype in homozygous and compound heterozygous FA is determined by residual frataxin levels rather than unique mutations.

Read more HERE

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