Accept Cookies?
Provided by OpenGlobal E-commerce

Please wait while your page loads ...

 

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.


Effects of Fe 2+/Fe 3+ Binding to Human Frataxin and Its D122Y Variant, as Revealed by Site-Directed Spin Labeling (SDSL) EPR Complemented by Fluorescence and Circular Dichroism Spectroscopies

Frataxin's actual physiological function has been debated for a long time without reaching a general agreement; however, it is commonly accepted that the protein is involved in the biosynthetic iron-sulfur cluster (ISC) machinery, and several authors have pointed out that it also participates in iron homeostasis. In this work, site-directed spin labeling coupled to electron paramagnetic resonance (SDSL EPR) is used to add new information on the effects of ferric and ferrous iron binding on the properties of human frataxin in vitro. Using SDSL EPR and relating the results to fluorescence experiments commonly performed to study iron binding to FXN, the authors produced evidence that ferric iron causes reversible aggregation without preferred interfaces in a concentration-dependent fashion, starting at relatively low concentrations (micromolar range), whereas ferrous iron binds without inducing aggregation. Moreover, our experiments show that the ferrous binding does not lead to changes of protein conformation. The data reported in this study reveal that the currently reported binding stoichiometries should be taken with caution. The use of a spin label resistant to reduction, as well as the comparison of the binding effect of Fe2+ in wild type and in the pathological D122Y variant of frataxin, allowed the characterization of the Fe2+ binding properties of different protein sites and highlight the effect of the D122Y substitution on the surrounding residues. The authors suggest that both Fe2+ and Fe3+ might play a relevant role in the context of the proposed FXN physiological functions.

Read the Full article here

Efficacy and Tolerability of Interferon Gamma in Treatment of Friedreich's Ataxia: Retrospective Study

Interferon-gamma (IFN-γ) has been shown to induce frataxin production in many cell types. In this study, the clinical features, tolerability, and the prognosis of individuals with FRDA to whom IFN-γ was administered in a university hospital were evaluated retrospectively and the results were discussed. To the best of our knowledge, this is the first study conducted in our country to evaluate the effect of IFN gamma on this patient group.

Read the Full article here

Exicure Provides Neuroscience Pipeline Update at Virtual R&D Day

CHICAGO & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Exicure, Inc. (NASDAQ: XCUR), the pioneer in gene regulatory and immunotherapeutic drugs utilizing spherical nucleic acid (SNA™) technology, announced that it will host a virtual R&D Day on Thursday, January 7th, 2021 from 09:00 am to 10:30 am ET to discuss Exicure’s neuroscience pipeline, including its lead program for Friedreich’s Ataxia which has progressed into IND-enabling studies.

Exicure’s Scientific Advisory Board member Dr. Susan Perlman and the CEO of the Friedreich’s Ataxia Research Alliance (FARA) Jennifer Farmer, will join Exicure’s leadership team in discussing the company’s progress in Friedreich’s Ataxia and its expanding neuroscience pipeline.

Read the Full article here

Thioredoxin and Glutaredoxin Systems as Potential Targets for the Development of New Treatments in Friedreich's Ataxia

The thioredoxin family consists of a small group of redox proteins present in all organisms and composed of thioredoxins (TRXs), glutaredoxins (GLRXs) and peroxiredoxins (PRDXs) which are found in the extracellular fluid, the cytoplasm, the mitochondria and in the nucleus with functions that include antioxidation, signaling and transcriptional control, among others. The importance of thioredoxin family proteins in neurodegenerative diseases is gaining relevance because some of these proteins have demonstrated an important role in the central nervous system by mediating neuroprotection against oxidative stress, contributing to mitochondrial function and regulating gene expression. Specifically, in the context of Friedreich's ataxia (FRDA), thioredoxin family proteins may have a special role in the regulation of Nrf2 expression and function, in Fe-S cluster metabolism, controlling the expression of genes located at the iron-response element (IRE) and probably regulating ferroptosis. Therefore, comprehension of the mechanisms that closely link thioredoxin family proteins with cellular processes affected in FRDA will serve as a cornerstone to design improved therapeutic strategies.

Read the Full article here

Minoryx's clinical candidate leriglitazone shows clinical benefit in a proof of concept Phase 2 study in Friedreich's ataxia

MIN-102 (leriglitazone) is an orally bioavailable selective PPAR gamma agonist that is one of the metabolites of pioglitazone and has been shown to have improved access to the central nervous system and better safety profile. Several research studies in both animal and cell models have identified that the peroxisome-proliferator activator receptor gamma (PPARγ)/PPARγ coactivator 1 alpha (Pgc1a) pathway is dysregulated when there is frataxin deficiency thus making this pathway a potential therapeutic target for FA.

Minoryx Therapeutics conducted a clinical trial that was a multicenter, double-blind and placebo-controlled study with leriglitazone. 39 Friedreich's ataxia patients were enrolled, with 32 completing the study. Today they announced that topline results show improvement of relevant disease biomarkers in the brain and spinal cord in this proof of concept Phase 2 study. Treatment with leriglitazone resulted in PPARg engagement, within the target range, in all patients as assessed by the relevant biomarker (adiponectin). Results of the trial show modulation of the Frataxin pathway and restoration of the bioenergetics deficits by leriglitazone in Friedreich's ataxia patients. They also reported that leriglitazone was well tolerated with some anticipated adverse events (side-effects) known to drugs with this mechanism of action.

Minoryx indicates that based on these results they are advancing the program and will be meeting with regulatory agencies, FDA and EMA, and planning a confirmatory study in FA.

Thank you to all of the individuals with FA who volunteered, investigators, and study sites for your participation and conduct of this important research trial and to Minoryx for their commitment to developing treatments for FA and their efficiency and transparency in sharing results from the trial. In the coming months, as Minoryx Therapeutics determines the next steps for the clinical development of this program, we will share that information with the community.

Click here to read the full press release

Page 10 of 212

SHARE

FacebookTwitterLinkedInYoutube
kyle-friend-eb.jpg

 

Archived in
  Scientific News


 

 

Tagged in
FARA Scientific News


Site Map     Privacy Policy      Service Terms      Contact      Charity Navigator