title: Thiazolidinediones under preclinical and early clinical development for the treatment of Parkinson's disease.
abstract: BACKGROUND
  Current treatment of Parkinson's disease (PD) is limited to symptomatic dopaminergic therapy, while no interventions have been shown to slow down disease progression.
  
  
  METHODS
  The following article highlights a group of PPAR-γ agonists called thiazolidinediones (TZDs), which are currently being tested for a putative disease-modifying benefit in PD, using pioglitazone as a prototypic compound. PPAR-γ is highly expressed in neurons of the substantia nigra and CNS immune cells. Preclinical data in rodent and primate support an effect of TZDs in preventing and/or arresting neurodegeneration and development of motor symptoms. Although no data on the neuroprotective effect of TZDs is currently available, a clinical trial is ongoing where the primary objective is to assess pioglitazone's impact on the progression of PD. The trial is also evaluating the drug's safety concerns.
  
  
  CONCLUSIONS
  The efficacy data from clinical trials must be carefully weighed against the safety concerns. However, given the solid preclinical data, and since the safety data are not yet fully conclusive and limited to the diabetic population, PPAR-γ research in PD can continue with caution. Ideally, drug discovery and development efforts will lead to the identification of new compounds with reduced risk of peripheral side effects.
authors.affiliation: University of Cagliari, Department of Biomedical Sciences , via Ospedale 72, 09124, Cagliari , Italy +39 0706758662 ; +39 0706758665 ; acarta@unica.it.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Carta
authors.forename: Tanya
authors.initials: T
authors.lastname: Simuni
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D018450:Disease Progression; D004298:Dopamine / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006801:Humans; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D047495:PPAR gamma / Q000819:agonists; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000978:Antiparkinson Agents; D018696:Neuroprotective Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D004298:Dopamine; D000077205:Pioglitazone
keywords: PPAR-γ; Parkinson; antidiabetic; pioglitazone; thiazolidinedione