ICAR 2022 – Registration is Open! |
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You can now submit late-breaking abstracts for ICAR until September 8, 2022, by clicking here.
To view late-breaking abstract guidelines click here.
The conference will be held on November 1-4, 2022, at Renaissance Dallas Addison Hotel in Dallas, Texas, USA. Register here before October 1st, 2022 to avoid the late fee.
You can view the preliminary program and invited speakers here.
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Reata Pharmaceuticals Announces Three Month Extension of the Review Period for New Drug Application for Omaveloxolone for the Treatment of Friedreich’s Ataxia
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Reata Pharmaceuticals, announced that they received a communication from the U.S. Food and Drug Administration informing them that they have extended the review timeline for the New Drug Application (“NDA”) for omaveloxolone for the treatment of Friedreich’s ataxia by three months.
Reata recently submitted an updated Delayed-Start Analysis of the MOXIe Extension study using a March 2022 data cut-off, a new Propensity-Matched Analysis of MOXIe Extension data using patient data from the Clinical Outcome Measures in Friedreich’s Ataxia Study ("FA-COMS") as controls, and an analysis of the relevance of Nrf2, the target of omaveloxolone, to the pathophysiology of Friedreich’s ataxia. These submissions were provided as confirmatory evidence of the results of the MOXIe Part 2 study in response to concerns raised by the FDA during the mid-cycle communication meeting. FDA determined that these submissions were a major amendment to the NDA and extended the Prescription Drug User Fee Act (“PDUFA”) date to provide time for a full review of the new data and analyses. The updated PDUFA date for the application is February 28, 2023. Click here to read the full press release.
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Recent FARA Funded FA Publications
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Natural History of Friedreich's Ataxia: Heterogeneity of Neurological Progression and Consequences for Clinical Trial Design.
Rummey C, Corben LA, Delatycki M, Wilmot G, Subramony SH, Corti M, Bushara K, Duquette A, Gomez C, Hoyle JC, Roxburgh R, Seeberger L, Yoon G, Mathews K, Zesiewicz T, Perlman S, Lynch DR.
The goal of this work was to acknowledge the broad genetic diversity of the FA 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), results from the modified Friedreich's Ataxia Rating Scale and its sub scores are presented. 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.
Cerebrospinal Fluid Proteomics in Friedreich Ataxia Reveals Markers of Neurodegeneration and Neuroinflammation.
Imbault V, Dionisi C, Naeije G, Communi D, Pandolfo M.
This study aimed to identify changes in cerebrospinal fluid (CSF) proteins occurring in FRDA patients that may be potential biomarkers in therapeutic trials. This study supports the hypothesis that the quantitative analysis CSF proteins may provide robust biomarkers for clinical trials as well as shed light on pathogenic mechanisms. Interestingly, differentially expressed proteins in FA patients CSF point to neurodegeneration and neuroinflammation processes that may respond to treatment.
Skin fibroblast metabolomic profiling reveals that lipid dysfunction predicts the severity of Friedreich’s ataxia.
Wang D, Ho ES, Cotticelli MG, Xu P, Napierala JS, Hauser LA, Napierala M, Himes BE, Wilson RB, Lynch DR, Mesaros C.
This study presents metabolic and lipidomic profiling by liquid-chromatography high resolution-mass spectrometry in FRDA patient-derived fibroblast cells. The authors found elevated HMG-CoA and β-hydroxybutyrate-CoA levels, implying dysregulated fatty acid oxidation. Lipidomic profiling identified dysregulated levels of several lipid classes in FRDA fibroblast cells when compared with non-FRDA fibroblast cells. This lipid dysfunction predicted the severity of FRDA.
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Frataxin Deficit Leads to Reduced Dynamics of Growth Cones in Dorsal Root Ganglia Neurons of Friedreich's Ataxia YG8sR Model: A Multilinear Algebra Approach.
Muñoz-Lasso DC, Mollá B, Sáenz-Gamboa JJ, Insuasty E, de la Iglesia-Vaya M, Pook MA, Pallardó FV, Palau F, Gonzalez-Cabo P.
In this paper, a computational multilinear algebra approach was used to analyze the dynamics of the growth cone and its function in control and FRDA neurons. The authors show that the deficiency of frataxin has an adverse effect on the formation and, most importantly, the growth cones' function in adult DRG neurons.
Metabolomics analysis reveals dysregulation in one carbon metabolism in Friedreich Ataxia.
O'Connell TM, Logsdon DL, Payne RM.
This paper reports results of metabolomic analyses of human patients with FA and identifies 59 unique metabolites that were significantly different between blood of FA patients and controls. 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.
Myocardial strain analysis by cardiac magnetic resonance 3D feature-tracking identifies subclinical abnormalities in patients with neuromuscular disease and no overt cardiac involvement.
Azzu A, Antonopoulos AS, Krupickova S, Mohiaddin Z, Almogheer B, Vlachopoulos C, Pantazis A, Pennell DJ, Mohiaddin RH.
The authors explored the value of 2D- and 3D-left ventricular myocardial strain analysis using feature-tracking - Cardiovascular magnetic resonance to detect subclinical cardiac involvement in neuromuscular diseases NMD.
Safety and pharmacokinetics of a highly bioavailable resveratrol preparation (JOTROL TM).
Kemper C, Benham D, Brothers S, Wahlestedt C, Volmar CH, Bennett D, Hayward M.
This paper describes a first in human study to evaluate the bioavailability of resveratrol after ascending, single oral doses up to 700 mg resveratrol as JOTROLTM. JOTROLTM is a micellar 10% resveratrol solubilization formulation that is thought to increase bioavailability of resveratrol via lymphatic system absorption. Jupiter Neurosciences is pursuing the use of resveratrol in mucopolysaccharidosis type 1, Friedreich's ataxia, and Alzheimer's disease/mild cognitive impairment.
Importance of an echocardiogram in the evaluation of ataxia.
Stokreef S, Lemos M, Quintas S.
The authors present the case of a boy in his middle childhood with gait ataxia and loss of reflexes with a 1-year onset. Even though he had no cardiac symptoms and a normal electrocardiography, the echocardiogram revealed severe asymmetric left ventricle hypertrophy consistent with hypertrophic cardiomyopathy. This prompted genetic testing and the diagnosis of Friedreich's ataxia was confirmed.
Structural and Functional Characterization of CreFH1, the Frataxin Homolog from Chlamydomonas reinhardtii.
Terenzi A, Pagani MA, Gomez-Casati DF, Busi MV.
The authors identified the gene CreFH1, which codes for the frataxin homolog from Chlamydomonas reinhardtii. They performed the cloning, expression and biochemical characterization of CreFH1.
Clinical and Molecular Spectrum of Degenerative Cerebellar Ataxia: A Single Centre Study.
Balakrishnan S, Aggarwal S, Muthulakshmi M, Meena AK, Borgohain R, Mridula KR, Yareeda S, Ranganath P, Dalal A.
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.
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FARA Newly Awarded Research Grants
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Postdoctoral Research Award
Anna Stepanova, PhD (Weill Cornell Medical College)
Calcium communication among intracellular compartments in FA patient-derived cells
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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. Here are the next dates:
September 13, 2022 – 12:00PM ET
Erin Seifert, Thomas Jefferson University
October 11, 2022 – 12:00PM ET
Damon Feng, Watts Lab, UMass Medical School
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The LOI must explain how the proposed research addresses FARA’s grant program priorities and should be sufficiently detailed to allow the reader to understand the validity and applicability of the project. Only selected LOIs will be invited to submit a full application. This is a competitive, peer-reviewed process, as such only a small number of applications are accepted past the LOI phase.
NIH funding opportunities, R03, Small Grant Program: The purpose of this funding opportunity announcement is to solicit applications for pilot projects to elucidate a role for understudied proteins associated with rare diseases. Awards will support generation of preliminary data and/or tools around eligible understudied protein(s). The next application deadline is October 17, 2022
Other grant opportunities from CIRM can be found HERE.
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Meetings of Interest to the FA Community |
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ASHG 2022 October 25-29, 2022 Los Angeles, CA
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