Accept Cookies?
Provided by OpenGlobal E-commerce

Please wait while your page loads ...

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.

 


 

Identification of a novel missense mutation in Friedreich's ataxia -FXNW 168R

Friedreich's ataxia, characterized by decreased expression of frataxin protein, is caused by GAA trinucleotide repeats within intron 1 in 98% of patients. Two percent of patients carry GAA repeats in conjunction with a point mutation. In this work, the authors find that frataxinW168R, a novel disease-causing missense mutation, is expressed predominantly as the intermediate frataxin42-210 form, with very little expression of mature frataxin81-210 form. Its localization to mitochondria is not impaired. Additionally, increasing frataxinW168R precursor levels do not lead to an increase in mature frataxin levels, suggesting these patients will require alternative approaches to repair frataxin processing in order to treat the disorder in a disease-modifying manner.

Read the entire article HERE

Mechanism of frataxin "bypass" in human iron-sulfur cluster biosynthesis with implications for Friedreich's ataxia

In humans, mitochondrial iron-sulfur (Fe-S) cluster biosynthesis is an essential process mediated by the assembly complex. The protein frataxin (FXN) is an allosteric activator that binds the assembly complex and stimulates the assembly activities. FXN depletion causes loss of activity of Fe-S-dependent enzymes and the development of the neurodegenerative disease Friedreich's ataxia. Recently, a mutation that suppressed the loss of the FXN homolog in yeast was identified that encodes an amino acid substitution equivalent to the human variant ISCU2 M140I. Here, we developed Fe-S cluster synthesis and transfer functional assays and determined that the human ISCU2 M140I variant can substitute for FXN in accelerating the rate of Fe-S cluster formation. Incorporation of both FXN and the M140I substitution had an additive effect, suggesting an acceleration of distinct steps in Fe-S cluster biogenesis. In contrast to the canonical role of FXN in stimulating the formation of [2Fe-2S]-ISCU2 intermediates, we found here that the M140I substitution in ISCU2 promotes the transfer of Fe-S clusters to GRX5. Together, these results reveal an unexpected mechanism that replaces FXN-based stimulation of the Fe-S cluster biosynthetic pathway and suggest new strategies to overcome the loss of cellular FXN that may be relevant to the development of therapeutics for Friedreich's ataxia.

Read the entire article HERE

Randomized, double-blind, placebo-controlled study of interferon-γ 1b in Friedreich Ataxia

In vitro, in vivo, and open-label studies suggest that interferon gamma (IFN-γ 1b) may improve clinical features in Friedreich Ataxia through an increase in frataxin levels. The present study evaluates the efficacy and safety of IFN-γ 1b in the treatment of Friedreich Ataxia through a double-blind, multicenter, placebo-controlled trial. Ninety-two subjects with FRDA between 10 and 25 years of age were enrolled. Subjects received either IFN-γ 1b or placebo for 6 months. The primary outcome measure was the modified Friedreich Ataxia Rating Scale (mFARS). No difference was noted between the groups after 6 months of treatment in the mFARS or secondary outcome measures. No change was noted in buccal cell or whole blood frataxin levels. However, during an open-label extension period, subjects had a more stable course than expected based on natural history data. This study provides no direct evidence for a beneficial effect of IFN-γ1b in FRDA. The modest stabilization compared to natural history data leaves open the possibility that longer studies may demonstrate benefit.

Read the entire article HERE

Therapeutic Prospects for Friedreich's Ataxia

Friedreich's ataxia (FRDA) is a progressive disease affecting multiple organs that is caused by systemic insufficiency of the mitochondrial protein frataxin. Current therapeutic strategies aim to elevate frataxin levels and/or alleviate the consequences of frataxin deficiency. Recent significant advances in the FRDA therapeutic pipeline are bringing patients closer to a cure.

Read the entire article HERE

StrideBio and Takeda Sign Collaboration and License Agreement to Advance Novel Gene Therapies for Neurological Diseases

DURHAM, N.C., March 28, 2019 /PRNewswire/ -- StrideBio, Inc, a leading developer of novel adeno-associated viral (AAV) based gene therapies, today announced the signing of a collaboration and license agreement with Takeda Pharmaceutical Company Limited (Takeda) to develop in vivo AAV based therapies for Friedreich's Ataxia (FA) and two additional undisclosed targets. These programs aim to utilize novel AAV capsids developed by StrideBio to improve potency, evade neutralizing antibodies and enhance specific tropism to tissues including the central nervous system.

"We are very excited to partner with Takeda given their expertise and commitment to developing treatments for patients with neurological diseases," stated Sapan Shah, Ph.D. Chief Executive Officer, StrideBio, Inc. "We look forward to working together to bring transformative and novel AAV-based gene therapies to patients, while continuing to validate and expand StrideBio's platform, manufacturing capabilities and pipeline."

Read the entire article HERE

Page 4 of 164

SHARE

FacebookTwitterLinkedInYoutube
Event G.jpg

 

Archived in
  Scientific News


 

 

Tagged in
FARA Scientific News