The therapeutic potential of targeting ferroptosis in the treatment of mitochondrial cardiomyopathies and heart failure

Cantrell AC, Zeng H, Chen JX. The therapeutic potential of targeting ferroptosis in the treatment of mitochondrial cardiomyopathies and heart failure. J Cardiovasc Pharmacol. 2023 Oct 10. doi: 10.1097/FJC.0000000000001496. Epub ahead of print. PMID: 37816193. 

We provide a brief overview of the potential roles of SIRT3 in mitochondrial iron homeostasis, as well as its contribution to the mitochondrial cardiomyopathy of Friedreich's ataxia (FRDA) and diabetic cardiomyopathy (DCM).

End-of-Life Discussions With Patients and Caregivers Affected By Neurogenetic Diseases

Anne-Claire D, Coarelli G, Heinzmann A, Verdon B, Manuella L, Petit E, Pierron L, Levy-Soussan M, Durr A, Gargiulo M, Ewenczyk C. End-of-Life Discussions With Patients and Caregivers Affected By Neurogenetic Diseases. Neurol Clin Pract. 2023 Dec;13(6):e200199. doi: 10.1212/CPJ.0000000000200199. Epub 2023 Oct 16. PMID: 37854177; PMCID: PMC10581072. DIRAGENE is an observational, cross-sectional, mixed-methods study with a patient-centered component and a primary caregiver-centered component. Observations include disease severity, psychosocial, and emotional scales; in-house questionnaires; and semidirected interviews.

 

Rehabilitation Program on Genetic and Degenerative Ataxia (RAPP)

ClinicalTrials.gov ID NCT06089863. Sponsor Hospices Civils de Lyon.

The present protocol aimed at evaluating the Rehabilitation Program in collaboration with partner patient on the symptom intensity, activity and quality of life on genetic and degenerative ataxia. 

This PAMPERO program's effect will be assessed by comparing the difference of Intensity of symptom measured by to Scale for the Assessment and Rating of Ataxia (SARA) at inclusion and 3 months after the end of rehabilitation.

Detection of alternative DNA structures and its implications for human disease

Matos-Rodrigues G, Hisey JA, Nussenzweig A, Mirkin SM. Detection of alternative DNA structures and its implications for human disease. Molecular Cell. 2023 Oct;83(20):3622-3641. DOI: 10.1016/j.molcel.2023.08.018. PMID: 37863029. 

 The most well-known REDs include Huntington’s disease (HD), fragile X syndrome (FXS), and Friedreich’s ataxia (FRDA), which are caused by the expansion of (CAG)n, (CGG)n, and (GAA)n repeats, respectively. Thus, DNA sequences prone to formalternative DNA structures are highly frequent in the human genome and associated with several human diseases.

Therapeutic Biomarkers in Friedreich's Ataxia: a Systematic Review and Meta-analysis

Gavriilaki M, Chatzikyriakou E, Moschou M, Arnaoutoglou M, Sakellari I, Kimiskidis VK. Therapeutic Biomarkers in Friedreich's Ataxia: a Systematic Review and Meta-analysis. Cerebellum. 2023 Oct 27. doi: 10.1007/s12311-023-01621-6. Epub ahead of print. PMID: 37889470.

 Although a large array of biomarkers have been investigated in Friedreich's ataxia (FRDA) trials, the optimal biomarker for assessing disease progression or therapeutic benefit has yet to be identified.

Experimental drugs for Friedrich’s ataxia: progress and setbacks in clinical trials, Expert Opinion on Investigational Drugs

Sylvia Boesch & Elisabetta Indelicato (2023) Experimental drugs for Friedrich’s ataxia: progress and setbacks in clinical trials, Expert Opinion on Investigational Drugs, DOI: 10.1080/13543784.2023.2276758 

 Generally, therapeutic approaches in FA are divided in two categories. One group of therapeutics (including gene therapy) aims at increasing/restoring frataxin levels. The second group encompasses those approaches aiming at reversing the consequence of frataxin loss at a tissue level, for instance mitochondrial failure. The first class of therapeutics may appear the most appealing as they intervene very early in the pathogenic cascade and may be potentially curative. Currently, various gene therapy and genome editing strategies are explored in FA. The likelihood of toxicity issues when overexpressing frataxin and the need for a delivery system with widespread distribution and low immunogenicity are among the hurdles to be addressed. Beyond these biological hinders, it is however not clear when such treatments should be administered to guarantee a reversal or at least a substantial improvement of the clinical phenotype. The presence of a developmental aspect as well as of a neurodegenerative kind of progression after onset suggest that the benefit of gene therapy/genome editing would be limited if applied beyond an early clinical phase.