title: Could thiazolidinediones increase the risk of heart failure in Friedreich's ataxia patients?
abstract: Clinical evidence and the recent decisions of the European Medicines Agency and the Food and Drug Administration challenge the safety of thiazolidinediones treatment. Recently, this treatment has been suggested for Friedreich's ataxia because thiazolidinediones improve neurological symptoms. Hypertrophic cardiomyopathy is the most prevalent cardiac feature and the cause of premature death in Friedreich's ataxia patients. We recommend that therapy with peroxisome proliferator-activated receptor-gamma agonists like thiazolidinediones be taken with caution, as they cause a decrease in the number of fast fibers and an increase in mitochondrial biogenesis in cardiac muscle because of the induction of peroxisome proliferator-activated receptor-gamma coactivator-1α. Furthermore, the incidence of heart failure may increase when thiazolidinediones are combined with insulin, and moreover, they produce cyclooxygenase 2 inhibition, inducing a thrombotic response. Thus, patients are predisposed to adverse cardiovascular outcomes. In our opinion, the possible fatal consequences must be taken into account when peroxisome proliferator-activated receptor-gamma agonist drugs are considered as possible therapeutic agents for Friedreich's ataxia patients.
authors.affiliation: CIBERER, Biomedical Network Research Centre on Rare Diseases, Valencia, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: García-Giménez
authors.forename: Fabián
authors.initials: F
authors.lastname: Sanchis-Gomar
authors.forename: Federico V
authors.initials: FV
authors.lastname: Pallardó
mesh_terms: D000818:Animals; D005621:Friedreich Ataxia / Q000150:complications* / Q000178:diet therapy / Q000188:drug therapy*; D006333:Heart Failure / Q000139:chemically induced*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D008954:Models, Biological; D047495:PPAR gamma / Q000378:metabolism; D012307:Risk Factors; D045162:Thiazolidinediones / Q000009:adverse effects*
chemical_list: D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones