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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.


Clinical and Molecular Spectrum of Degenerative Cerebellar Ataxia: A Single Centre Study

Cerebellar ataxia is a disabling neurological symptom with extreme clinical and etiological heterogeneity. The objective of this study is to investigate the clinical and molecular characteristics in patients with degenerative cerebellar ataxia. 150 South-Indian patients with degenerative cerebellar ataxia underwent a phenotype guided, sequential tiered testing. Phenotypic features studied included cerebellar symptoms, pyramidal and extrapyramidal features, and ophthalmic and systemic findings. Tier one included conventional tests such as short PCR/fragment analysis for spinocerebellar ataxia (SCA) subtypes 1, 2, 3, 6, 7, 8, 12, 17, and 36 and TP-PCR for Friedreich ataxia (FA). Tier two testing comprised next-generation sequencing (NGS)-based strategies reserved for select undiagnosed cases. The clinical features were highly overlapping and had limited specificity, except in autosomal recessive ataxias and SCA 34. The overall diagnostic yield of our study was 49.3%. SCA 1, 2, and 3 were noted in 13 (12.6%), 12 (11.6%) and 14 (13.5%), respectively, out of the 103 tested, and FA was noted in 17/55 (30.9%) patients. SCA subtypes 6, 7, 8, 12, 17, and 36 were absent in the cohort studied. Targeted Sanger sequencing and NGS revealed some rare diagnoses in 17 among the 18 patients tested. Whole exome sequencing uncovered a novel genotype-phenotype association in a sibling-pair with ataxia, dysmorphism, and retinopathy. SCA 1, 2, 3 and FRDA were the most common causes of ataxia. SCA 6, 7, 8, 12, 17, and 36 were absent in the cohort studied. NGS testing revealed several rare forms of ataxia. Clinical features based testing is cost-effective, achieves good genotype-phenotype correlation, and prioritizes variants for further studies.

Read the Full article here
 

FARA General Research Grants - LOI Deadline is Aug 15th!

FARA General Research Grants
Letter of Intent Deadline
August 15, 2022

The deadline for Letters of Intent (LOIs) within the FARA grant program is approaching on August 15. Submissions for General Research Grants, Postdoctoral Awards, and Postdoctoral Fellowships are being accepted. FARA supports research through funding competitive grants across the spectrum from basic research through drug development and clinical research programs in Friedreich's Ataxia (FA).

In 2020/2021, about 50% of LOIs received were invited to submit a full application. All investigators interested in FA-related research are invited to submit an LOI through our submission portal. The proposed research must fall within FARA's Grant Program Priorities and more information on how to apply for a FARA grant can be found here.

Please note the grant funding start dates for each cycle and select your submission cycle accordingly.
 
 

Meet the team at University of Florida for the TRACK-FA Study

Track FA Study Team Photo
Who are the team members?
Manuela Corti, PhD; Asst Professor of Pediatrics and Associate Director of Powell Gene Therapy Center
S H Subramony, MD; Professor of Neurology and Pediatrics
Thomas Mareci, PhD; Professor, Department of Biochemistry and Molecular Biology
Mackenzi Coker, MS, CCC-SLP; Clinical Research Coordinator, Department of Pediatrics
Samantha Norman, MPH, BS; Clinical Research Coordinator, Department of Pediatrics

How long has the UF Team been working on FA?
Dr. Corti has worked on FA for over 10 years based on her interests in bringing gene therapy to several neuromuscular disorders. Dr. Subramony has been involved with FA for over 25 years as part of broad interest in inherited ataxias and was instrumental in developing early outcome measures. Dr. Mareci is an expert in MRI technology and has worked on imaging studies of ataxias for over 5 years. Mackenzie Coker and Sam Norman bring expertise in clinical research coordination in genetic diseases

Who was the first fellow FA researcher you met?
Dr. Subramony was the first FA researcher that Dr. Corti met. During the last 10 years, she has interacted with other FA researchers in the United States, Australia and Europe. Dr. Subramony has interacted with many FA researchers for many years including Drs Lynch, Perlman and Bidichandani and has been member of Collaborative Clinical Research Network in FA since its conception.

What got you interested in FA research?
Dr. Corti started a gene therapy program with Dr. Barry Byrne, the Powell Gene Therapy Center’s director, in FA after the mother of an FA affected individual, approached them about working toward developing gene therapy for FA. Through a community fundraiser, a pilot research program was initiated at the University of Florida. The UF FA research team has since been awarded multiple grants from patient foundations and industry partners. The ultimate aim of the program is to bring direct gene replacement to FA patients, at the same time offering opportunities for other research studies and clinical trials. These efforts are helped by the excellent facilities at UF, especially the Powell Gene Therapy Center (PGTC) and Clinical and Translational Science Institute (CTSI).

Dr. Subramony became involved in genetic ataxias in the late 1980s and 1990s, oversaw one of the early ataxia focused clinics at the University of Mississippi and evaluated and genotyped many families with FA and SCAs. After coming to UF in 2009, it was a natural event to collaborate with the Powell Gene Therapy Center.

What got you interested in imaging in FA?
Having realized the limitations of clinical outcome measures in FA, there is major interest in biomarkers with imaging being a prime candidate. At UF, this interest could be fostered easily by the presence of the research only facility, Advanced Magnetic Resonance Imaging and Spectroscopy facility (AMRIS), and the scientists associated with it. Dr. Mareci had already participated in multi-center MRI studies of spinocerebellar ataxias. This expertise was easily adapted for the TRACK-FA study. TRACK-FA is one of a number of other research imaging studies in genetic neuromuscular diseases at AMRIS, including cardiac imaging in FA.

What do you hope to achieve with TRACK-FA?
We fervently hope that the findings in this study will speed up and facilitate upcoming clinical trials of novel therapeutics including gene therapy in FA.

How would you like to encourage FA patients to participate at your site?
Gainesville is a wonderful “college” town with many sporting and cultural activities associated with the university. There are many museums and restaurants and if you time your visit, you can watch competitive University sports such as football. TRACK-FA visits take place in the Clinical and Translational Science building, a state-of-the-art research building which is uncluttered and pleasant, and the AMRIS imaging facility which is also utilized for research only and is beautiful in its own regards. Don’t forget that you can add a Florida vacation to your trip by driving to one the of beaches or to one of the many amusement parks in Orlando, all within 100 miles of Gainesville.

In addition, all FA patients coming to UF become family to us. We do everything we can to help FA patients to overcome some of the challenges that come with living with FA. We are always available to communicate with their medical providers, if needed, we are willing to help in identifying the best exercise program for them, we help with patient equipment needs to enhance safety and maintain autonomy. Furthermore, we are always available to discuss scientific questions related to upcoming research. And most importantly, we are always here for a laugh, a cry and simply for a chat.

How would a TRACK-FA visit look like at your site?
If coming for a TRACK-FA visit, you can look forward to a quality visit with our team. If it is your first visit to our site, you will be consented into the study by one of our study team members. From there we will collect some medical information, including your genetic confirmation and any medications you may be taking. We will then get some vitals as well as collect some blood from you.

Once the boring things are out of the way, we will then move into the functional and cognitive assessments. These assessments include the run of the mill mFARs, the SARA, the 9hpt, vision and speech testing. The cognitive assessments will include three brief questionnaires and we will discover your handedness. Your visit will be rounded out with the MRI which includes imaging of both the brain and spinal cord.

Read more about the study HERE
 

Natural History of Friedreich's Ataxia: Heterogeneity of Neurological Progression and Consequences for Clinical Trial Design

The understanding of the natural history of Friedreich's ataxia has improved considerably recently, but patterns of neurologic deterioration are not fully clarified, compromising the assessment of the clinical relevance of effects and guidance for study design. The goal of this work was to acknowledge the broad genetic diversity of the population, especially with respect to younger individuals and to provide analyses stratified by age to guide population selection in future studies. Based on a large natural history study, the Friedreich's Ataxia Clinical Outcome Measures study (FACOMS) that at the current data cut enrolled 1115 participants, followed up for 5287 yearly visits, results from the modified Friedreich's Ataxia Rating Scale and its sub scores are presented. Secondary outcomes included the patient-reported activities of daily living scale, the timed 25-foot walk and the 9-hole peg test. Long-term progression was modeled using slope analyses within Early, Typical, Intermediate and Late Onset Friedreich's Ataxia. To reflect recruitment in clinical trials, short term changes were analyzed within age-based sub-populations. All analyses were stratified by ambulation status. Long term progression models stratified by disease severity indicated highly differential disease progression, especially at earlier ages of onset. In the ambulatory phase, decline was driven by axial items assessed by the Upright Stability sub score of the mFARS. The analyses of short-term changes showed slower progression with increasing population age, as a result of decreasing genetic severity. Future clinical studies could reduce population diversity, inter-patient variability, and the risk of imbalanced treatment groups by selecting the study population based on the functional capacity (e.g., ambulatory status) and by strict age-based stratification. Understanding of the diversity within Friedreich's ataxia populations and their patterns of functional decline provides an essential foundation for future clinical trial design including patient selection and facilitates the interpretation of the clinical relevance of progression detected in Friedreich's ataxia.

Read the Full article here
 

Metabolomics analysis reveals dysregulation in one carbon metabolism in Friedreich Ataxia

Multiple therapeutic approaches are in development in FA, but a key limitation is the lack of biomarkers reflecting the activity of FXN in a timely fashion. The authors predicted this dysregulated metabolism would present a unique metabolite profile in blood of FA patients versus Controls (Con). Plasma from 10 FA and 11 age and sex matched Con subjects was analyzed by targeted mass spectrometry and untargeted NMR. This combined approach yielded quantitative measurements for 540 metabolites and found 59 unique metabolites (55 from MS and 4 from NMR) that were significantly different between cohorts. Correlation-based network analysis revealed several clusters of pathway related metabolites including a cluster associated with one carbon (1C) metabolism composed of formate, sarcosine, hypoxanthine, and homocysteine. Receiver operator characteristics analyses demonstrated an excellent ability to discriminate between Con and FA with AUC values >0.95. These results are the first reported metabolomic analyses of human patients with FA. The metabolic perturbations, especially those related to 1C metabolism, may serve as a valuable biomarker panel of disease progression and response to therapy. The identification of dysregulated 1C metabolism may also inform the search for new therapeutic targets related to this pathway.

Read the Full article here
 

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