The full program is now available here. You can still register at here and book your room at the Renaissance Dallas Addison Hotel here.
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Ataxia Global Conference 2022
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The Conference of the Ataxia Global Initiative (AGI) will take place on November 4th-5th, after ICAR. The AGI conference brings together academia, industry as well as patient advocacy organizations and will focus on trial-readiness for ataxias. It will be held in a hybrid form (except for the poster session). For more information and to register, visit the AGI website here.
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Larimar Therapeutics Announces FDA Clearance to Initiate the 25 mg Cohort of a Phase 2 Dose Exploration Trial of CTI-1601 in Friedreich’s Ataxia Patients
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Larimar Therapeutics, Inc. announced that the FDA has cleared the initiation of the 25 mg cohort of a Phase 2, four-week, placebo-controlled, dose exploration trial of CTI-1601 in Friedreich’s ataxia (FA) patients. In a written communication to Larimar, the FDA indicated it was lifting its full clinical hold on the CTI-1601 program and imposing a partial hold. The design of the upcoming Phase 2 trial is identical to the design proposed by Larimar, with the exception of a requirement for the FDA to review data from the 25 mg cohort prior to escalating the dose in the second cohort. Larimar expects to begin the Phase 2 trial in Q4 2022, with top-line data expected in 2H 2023. Learn more here.
Solid Biosciences Announces Acquisition of AavantiBio and Concurrent $75 Million Private Placement
Solid Biosciences and AavantiBio announced that the companies have entered into a definitive merger agreement whereby Solid will acquire AavantiBio, including its pipeline assets and net cash. The combined company will focus on advancing a portfolio of neuromuscular and cardiac programs, led by SGT-003, a differentiated gene transfer candidate, for the treatment of Duchenne. Additional pipeline programs include AVB-202, a gene transfer candidate for the treatment of Friedreich’s ataxia, AVB-401 for BAG3 mediated dilated cardiomyopathy, and additional assets for the treatment of undisclosed cardiac diseases. Learn more here.
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Recent FARA Funded FA Publications
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Activation of a type I interferon response associated with acute frataxin knockdown in iPSC-derived cardiomyocytes
Cotticelli MG, Xia S, Truitt R, Doliba NM, Rozo AV, Tobias JW, Lee T, Chen J, Napierala JS, Napierala M, Yang W, Wilson RB.
Transcriptome analysis of human cardiomyocytes derived from induced pluripotent stem cell with acute frataxin knockdown identified severe mitochondrial dysfunction and a type I interferon response as the pathways most affected by frataxin knockdown. The type I interferon response was caused, at least in part, by release of mitochondrial DNA into the cytosol, activating the cGAS-STING sensor pathway. Learn more here.
A non-synonymous single nucleotide polymorphism in SIRT6 predicts neurological severity in Friedreich ataxia
Rodden LN, Rummey C, Dong YN, Lagedrost S, Regner S, Brocht A, Bushara K, Delatycki MB, Gomez CM, Mathews K, Murray S, Perlman S, Ravina B, Subramony SH, Wilmot G, Zesiewicz T, Bolotta A, Domissy A, Jespersen C, Ji B, Soragni E, Gottesfeld JM, Lynch DR.
An exploratory analysis of DNA from 88 individuals with FRDA and a follow-up analysis of 569 subjects with FRDA suggested that an SNP (rs352493) in SIRT6 correlated with neurological severity in FRDA. Biochemical analyses indicate that the benefit conferred by T to C SNP in SIRT6 does not come from altered expression or enzymatic activity of SIRT6 or frataxin but is associated with changes in the transcriptome. Learn more here.
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Comorbidities in Friedreich ataxia: incidence and manifestations from early to advanced disease stages.
Fichera M, Castaldo A, Mongelli A, Marchini G, Gellera C, Nanetti L, Mariotti C.
In this study, the authors aimed to analyze the incidences of FA-related and unrelated comorbidities occurring in different stages of the disease progression.
The C-Terminal Cross-linked Telopeptide of Type I Collagen (CTX-I) as a Potential Cardiomyopathy Biomarker in Friedreich Ataxia Patients.
Pane C, Trinchillo A, Salzano A, Marsili A, Puorro G, Cittadini A, Saccà F, Russo CV.
The aim of this study was to measure serum type I collagen (CTX-I) as a marker of cardiac fibrosis in FRDA patients. CTX-I values were significantly higher in the patients than in the control group. The regression model identified disease duration and TT3 levels to be independent predictors of CTX-I.
Hyperactivation of mTOR and AKT in a cardiac hypertrophy animal model of Friedreich ataxia.
Tong WH, Ollivierre H, Noguchi A, Ghosh MC, Springer DA, Rouault TA.
This study shows increased phosphorylation of AKT and dysregulation of multiple downstream effectors of mTORC1 in a cardiac/skeletal muscle specific FRDA conditional knockout (cKO) mouse model and in human cell lines depleted of iron-sulfur cluster (ISC) biogenesis factors. Administration of rapamycin, a specific inhibitor of mTOR signaling, enhanced the survival of the Fxn cKO mice.
A promising mouse model for Friedreich Ataxia progressing like human patients.
Gérard C, Archambault AF, Bouchard C, Tremblay JP
The authors report here that the FRDA YG8-800 mice show progressively worsening locomotion and balance phenotypes starting at 11 to 20 weeks depending on the behavioral test. Moreover, these mice showed at 26 weeks a heart hypertrophy characterized by an increased heart to body weight ratio.
Diabetes mellitus and Friedreich´s ataxia in a child: a complicated coexistence.
Marqués Cabrero A, Expósito Raspeño M, Sánchez Escudero V, Gutiérrez Cruz N, González Vergaz A.
This is a report of a pediatric patient with Friedrich ataxia and diabetes mellitus.
The inherited cerebellar ataxias: an update.
Coarelli G, Wirth T, Tranchant C, Koenig M, Durr A, Anheim M.
This narrative review aims at providing an update on the management of inherited cerebellar ataxias, describing main clinical entities, genetic analysis strategies and recent therapeutic developments.
Respiratory Function in Friedreich's Ataxia
Vinante E, Colombo E, Paparella G, Martinuzzi M, Martinuzzi A.
This study aims to make an objective analysis of the respiratory condition of both early and late stage FRDA patients, looking for correlations with the motor, skeletal, speech and genetic aspects of this condition. Data show the presence of a recurrent pattern of respiratory dysfunction of a restrictive type, with reduction in forced vital capacity and of flow and pressure parameters.
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FARA Newly Awarded Research Grants
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General Research Grant-
Pharmacodynamic Biomarker Development RFP
David Lynch, MD, PhD (Children’s Hospital of Philadelphia)
Imaging of glutathione and GABA in the brain as biomarkers of Friedreich ataxia
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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 is the next date:
December 13, 2022 – 12:00PM ET
Erin Seifert, Thomas Jefferson University
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- KMA Cardiac Award, KB Translational Research Award and BJK International Research Collaboration Award – LOI deadline is January 15, 2023
- Award for Innovative Mindset – application deadline is February 1, 2023
- General Research Grants – next LOI deadline is February 15, 2023
See FARA grant program priorities HERE.
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 March 15, 2023.
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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