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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.


A Novel Solution-Gated Graphene Transistor Biosensor for Ultrasensitive Detection of Trinucleotide Repeats

A new way to detect GAA trinucleotide repeats (TNRs) based on a solution-gated graphene transistor (SGGT) with high performance was developed. Herein, a SGGT biosensor was constructed based on G-quadruplex DNAzymes and graphene channels. The DNAzymes quantify the captured target DNA by producing a strong catalytic current signal depending on the peroxidase-like activity. The higher the target DNA quantity captured on the gate electrode is, the higher is the concentration of DNAzymes on the surface of the gate electrode, which generates a high catalytic current. Due to the excellent self-amplifying performance of the transistor, the current signal of the SGGT is several hundreds of times larger than in conventional electrochemistry under identical detection conditions. Moreover, a large current signal can be obtained in the case of a low concentration of H2O2 when compared to the case of an enzyme-catalyzed transistor. The SGGT biosensor also exhibits an ultra-low detection limit (32.25 fM), a wide linear range (100 fM-100 nM), and excellent selectivity. The results show that the SGGT biosensor has great potential in the early diagnosis of neurodegenerative diseases.

Read the entire article HERE

New Request For Proposals: Therapeutic window of frataxin

FARA is announcing a request for proposals aimed at supporting therapeutic development in FA, by providing key preclinical data to support the development of benchmarks to improve the likelihood of success of frataxin delivery or upregulation.

Many therapeutic interventions in FA are aimed at elevating the levels of frataxin protein with small molecules or delivering frataxin to the affected tissues by means of gene, protein replacement or stem cell therapy. However, there are critical pre-clinical studies that must be done to ensure that these interventions are successful.

Applications focused on addressing one or more of the following outstanding questions will be considered:

  1. What are the levels of frataxin that are needed to restore function in cells and tissues supportive of therapeutic benefit?
  2. What is the percent of cells that need to be targeted in a tissue to achieve a clinical benefit and what is the effect of frataxin increase/delivery in a subset of cells within a tissue?
  3. What is the contribution of non cell-autonomous effects on therapeutic benefit for relevant tissues?
  4. What are the temporal aspects of frataxin increase/delivery?

Read the full RFP here.
The deadline for submission of a Letter of Intent is September 1st, 2020.
Please submit your LOI here.

Mitochondrial Damage and Senescence Phenotype of Cells Derived From a Novel Frataxin G127V Point Mutation Mouse Model of Friedreich's Ataxia

A prevalent missense mutation among Friedreich's ataxia (FRDA) patients changes a glycine at position 130 to valine (G130V). Herein, we report generation of the first mouse model harboring a Fxn point mutation. Changing the evolutionarily conserved glycine 127 in mouse Fxn to valine results in a failure to thrive phenotype in homozygous animals and a substantially reduced number of offspring. Like G130V in FRDA, the G127V mutation results in a dramatic decrease of Fxn protein without affecting transcript synthesis or splicing. FxnG127V mouse embryonic fibroblasts exhibit significantly reduced proliferation and increased cell senescence. These defects are evident in early passage cells and are exacerbated at later passages. Furthermore, increased frequency of mitochondrial DNA (mtDNA) lesions and fragmentation are accompanied by marked amplification of mtDNA in FxnG127V cells. Bioenergetics analyses demonstrate higher sensitivity and reduced cellular respiration of FxnG127V cells upon alteration of fatty acid availability. Importantly, substitution of FxnWT with FxnG127V is compatible with life and cellular proliferation defects can be rescued by mitigation of oxidative stress via hypoxia or induction of the NRF2 pathway. We propose FxnG127V cells as a simple and robust model for testing therapeutic approaches for FRDA.

Read the entire article HERE

HMTase Inhibitors as a Potential Epigenetic-Based Therapeutic Approach for Friedreich's Ataxia

Currently there is no effective treatment for Friedreich's ataxia (FRDA) and patients die prematurely. Recent findings suggest that abnormal GAA expansion plays a role in histone modification, subjecting the FXN gene to heterochromatin silencing. Therefore, as an epigenetic-based therapy, we investigated the efficacy and tolerability of two histone methyltransferase (HMTase) inhibitor compounds, BIX0194 (G9a-inhibitor) and GSK126 (EZH2-inhibitor), to specifically target and reduce H3K9me2/3 and H3K27me3 levels, respectively, in FRDA fibroblasts. We show that a combination treatment of BIX0194 and GSK126, significantly increased FXN gene expression levels and reduced the repressive histone marks. However, no increase in frataxin protein levels was observed. Nevertheless, our results are still promising and may encourage to investigate HMTase inhibitors with other synergistic epigenetic-based therapies for further preliminary studies.

Read the entire article HERE

Feasibility and Acceptability of Lee Silverman Voice Treatment in Progressive Ataxias

Communication difficulties have considerable impact on people with progressive ataxia, yet there are currently no evidence-based treatments. Lee Silverman Voice Treatment (LSVT LOUD®) focuses on the production of healthy vocal loudness whilst also improving breath support, vocal quality, loudness and articulation in participating patients. This study aimed to investigate whether LSVT LOUD® can improve communication effectiveness in these patients. We performed a rater-blinded, single-arm study investigating LSVT LOUD® treatment in a population of patients with progressive ataxia including Friedreich's ataxia (n = 18), spinocerebellar ataxia type 6 (n = 1), idiopathic cerebellar ataxia (n = 1), and spastic paraplegia 7 (n = 1). Twenty-one patients were recruited to the study, with 19 completing treatment. Sessions were administered via Skype in the LSVT-X format, meaning two sessions per week over a period of 8 weeks. Assessments included two baseline and two post-treatment measures and focused on outcome measures covering aspects ranging from physiological function to impact and participation. Results indicate improvements in patient-perceived outcomes for 14 of the 19 participants, in both speech and psychosocial domains. Speech data furthermore demonstrate significant improvements in prolonged vowel duration, and voice quality measures. Intelligibility and naturalness evaluations showed no change post-treatment. Patients reported high acceptability of the treatment itself, as well as administration by Skype. This is the largest treatment study for people with progressive ataxia published to date. It provides an indication that LSVT LOUD® can have a positive impact on communication in this patient group and could form the basis for larger-scale trials.

Read the entire article HERE

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