FARA Newly Awarded Research Grants |
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Awards for Innovative Mindset (AIM)
FARA and fara Australia are proud to announce the recipients of the Award for Innovative Mindset (AIM). AIM was designed to promote the initial exploration of high-risk, high-gain, and potentially groundbreaking concepts in FA research. 10 applications were received and 2 were awarded funding:
Nuclear frataxin and the regulation of macrophage activation
Marco Carpenter, PhD – Children’s Hospital of Philadelphia
Dentato-Thalamo-Cortical tracts in Friedreich Ataxia: impact of its modulation on Friedreich Ataxia symptoms and brain functional architecture
Gilles Naeije, MD, PhD - Université Libre de Bruxelles, Belgium
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Testing whether somatic GAA expansions are a therapeutic target for FRDA
Ricardo Mouro Pinto, PhD - Massachusetts General Hospital, Harvard Medical School and Caroline Benn, PhD – LoQus23 therapeutics
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Testing the efficacy of dietary butyrate in ameliorating ataxic symptoms in Friedreich’s ataxia mouse models
Daniele Lettieri-Barbato, PhD – University of Rome Tor Vergata, Italy
Co-sponsor AFAF
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FARA Grant Program Updates |
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FARA supports FA research and therapeutic development by funding competitive grants through the grant program, by proactively directing research in high priority areas, and by establishing institutional programs to provide a long-term commitment to research. These three funding mechanisms, the FARA Grant Program, the FARA Directed Projects and the Institutional Supported Programs sustain FARA’s strategic priorities and mission to marshal and focus the resources and relationships needed to treat and cure FA. As our research priorities are constantly evolving and as our therapeutic pipeline grows, FARA must carefully consider how to direct its financial resources, frequently reevaluate these allocations and quickly adapt and respond to shifts in knowledge of the disease and milestones in therapeutic development.
In the last few years, FARA has received 40 to 45 Letters of Intent (LOIs) per year and about half are invited to submit a full application. Because our financial resources are limited, the funding recommendations of FARA’s Scientific Review Committee are even more so guided by FARA research priorities. As such, the LOI selection has become more competitive and only LOIs that specifically address high priority research areas will be invited to submit a full application.
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FARA Funded Research, July 2021 |
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Friedreich Ataxia: Multidisciplinary Clinical Care
Lynch DR, Schadt K, Kichula E, McCormack S, Lin KY.
This review provides a summary of the diverse manifestation of FRDA, existing symptomatic therapies, and approaches for integrative care for future therapy in FRDA. The phenotype of FRDA is unique, giving rise to specific loss of neuronal pathways, a unique form of cardiomyopathy with early hypertrophy and later fibrosis, and diabetes incorporating components of both type I and type II disease. Vision loss, hearing loss, urinary dysfunction and depression also occur in FRDA. Many agents are reaching Phase III trials; if successful, these will provide a variety of new treatments for FRDA that will require many specialists who are not familiar with FRDA to provide clinical therapy.
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Other FA Research Publications, July 2021 |
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Molecular Details of the Frataxin-Scaffold Interaction during Mitochondrial Fe-S Cluster Assembly.
Campbell CJ, Pall AE, Naik AR, Thompson LN, Stemmler TL.
In this review, the authors focus on both frataxin and the FeS assembly scaffold protein ISCU within the human, fly and yeast model systems to provide a better understanding of the biophysical characteristics of each protein alone and within the FXN/ISCU complex as it exists within the larger NFS1, ISD11, ACP, ISCU and FXN complex. These details support a complex dynamic interaction between the FXN and ISCU proteins and provides additional insight into the coordinated mechanism of Fe-S cluster assembly.
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The Cost of Living with Inherited Ataxia in Ireland.
Kelly MJ, Bogdanova-Mihaylova P, Skeens J, Moran S, Farrelly S, Walsh RA, Murphy SM.
The aim of this study was to collect individual ataxia-related healthcare resources in a large cohort of individuals with different subtypes of inherited ataxia and calculate the associated cost of illness in the Republic of Ireland. Indirect costs, based on productivity losses by participants or caregivers, accounted for 52% of the cost of illness. Inherited ataxia is associated with significant health and social care costs.
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Myocardial Perfusion Reserve in Children with Friedreich Ataxia
Hutchens JA, Johnson TR, Payne RM.
This study used myocardial perfusion reserve (MPR), an MRI technique used to assess the maximal myocardial blood flow above baseline, to help determine potential surgical risk in FA subjects. This retrospective study shows that children with FA develop MPR defects early in the disease process. It also suggests MPR may be a sensitive tool to evaluate underlying cardiac compromise and could be of use in directing surgical management decisions in children with FA.
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Differential efficacies of Cas nucleases on microsatellites involved in human disorders and associated off-target mutations
Poggi L, Emmenegger L, Descorps-Declère S, Dumas B, Richard GF.
This study measured the efficacy of several CRISPR-Cas nucleases to induce recombination within disease-related microsatellites, in Saccharomyces cerevisiae. Broad variations in nuclease performances were detected on all repeat tracts. Wild-type Streptococcus pyogenes Cas9 (SpCas9) was more efficient than Staphylococcus aureus Cas9 on all repeats tested, except (CAG)33. Cas12a (Cpf1) was the most efficient on GAA trinucleotide repeats, whereas GC-rich repeats were more efficiently cut by SpCas9.
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Rare occurrence of severe blindness and deafness in Friedreich ataxia: a case report.
Damásio J, Sardoeira A, Araújo M, Carvalho I, Sequeiros J, Barros J.
This study describes an FA patient who at 22 years-old developed sensorineural deafness, and at 26 visual impairment. Visual acuity had a catastrophic deterioration, with blindness 3 years after visual impairment was first noticed. Audiograms documented progressive sensorineural deafness, most striking for low frequencies. Visual evoked potentials disclosed bilaterally increased P100 latency.
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Very late-onset Friedreich's ataxia with rapid course mimicking as possible multiple system atrophy cerebellar type.
Vidhale TA, Gupta HR, Pj R, Gandhi C.
This study reports a case of very late-onset Friedreich's ataxia with likely compound heterozygous genotype. Clinical assessment indicated mild cognitive decline with cerebellar, pyramidal and peripheral nerves involvement. Brain and whole spine MRI revealed widespread cerebral and mild cerebellar atrophy, pons and medulla volume loss, and a normal spinal cord. Transthoracic echocardiography revealed concentric left ventricular hypertrophy.
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Interruptions of the FXN GAA Repeat Tract Delay the Age at Onset of Friedreich's Ataxia in a Location Dependent Manner.
Nethisinghe S, Kesavan M, Ging H, Labrum R, Polke JM, Islam S, Garcia-Moreno H, Callaghan MF, Cavalcanti F, Pook MA, Giunti P.
This study reports the use of triplet repeat primed PCR (TP PCR) assays to identify small interruptions at the 5' and 3' ends of the GAA repeat tract through alterations in the electropherogram trace signal. Contrary to large interruptions, small interruptions are more common, with 3' interruptions being most frequent. Patients with 3' interruptions were associated with shorter GAA1 repeat tracts and later ages at disease onset.
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The FARA Forum is a monthly webinar featuring investigators who have been awarded FARA grants. The webinar is open to FARA grant awardees, and it is held on the second Tuesday of every month. Upcoming Dates:
September 14, 2021
12:00 PM EDT Ronald Crystal, Weill Cornell Medical College
12:45 PM EDT Shannon Boye, University of Florida
October 12, 2021
12:00 PM ET Robert Wilson, Children's Hospital of Philadelphia
12:45 PM ET Chad Heatwole, University of Rochester Medical Center
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Meetings of Interest to the FA Community |
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The NIH will hold a virtual, three-day workshop titled “Genetic Modifiers: Lessons from Nervous System Disorders” on September 21, 22, and 23 from 10 am – 2pm EST. More information here.
Neuroscience 2021, November 13-16, 2021 - McCormick Place Convention Center, Chicago.
Save the date for the inaugural International Congress for Ataxia Research (ICAR), March 15-18, 2022 - Orlando, Florida, USA.
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FARA research grants http://curefa.org/grant-types: Keith Michael Andrus Cardiac Award – next LOI deadline is January 15, 2022; General Research Grants – next LOI deadline is February 1, 2022. See FARA grant program priorities here
CIRM - Various grant opportunities for stem cell-related projects in California.
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Post-doctoral fellow position - Napierala Laboratory, University of Alabama at Birmingham
A post-doctoral fellow position is immediately available to study mechanisms of Friedreich’s ataxia in the Napierala Laboratory, within the Department of Biochemistry and Molecular Genetics at the University of Alabama at Birmingham. We are seeking a highly motivated scientist to join our multi-disciplinary group who is interested in investigating how chromatin changes are implicated in the pathogenesis of repeat expansion diseases.
The position requires experience utilizing mammalian cell culture models, and proficiency working with induced pluripotent stem cells is desirable. Preference will be given to candidates demonstrating expertise in chromatin biology, transcriptional regulation and post-translational histone modifications, including experience performing ChIP, ChIP-seq and RNAseq experiments.
The postdoctoral fellow duties will include but are not limited to: organizing and implementing complex research plans (independently and as part of a team), developing new methods, collecting and recording data, and analyzing and critically interpreting data. The successful candidate will be expected to possess excellent communication skills and present their research findings regularly to peers within the Department and at national and international meetings. The postdoctoral fellow will also participate in preparation of grant applications and publications.
We offer competitive pay at or above NIH recommended level and relocation assistance.
To be considered for this position, please email your CV and cover letter to mnapiera@uab.edu.
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