Details

Autor(en) / Beteiligte

• Jawaid, Ali
• Paganoni, Sabrina
• Schulz, Paul E

Titel

Trials of Anti-Diabetic Drugs in Amyotrophic Lateral Sclerosis: Proceed with Caution?

Ist Teil von

• Neuro-degenerative diseases, 2013-10, Vol.13 (4), p.205-208

Erscheinungsjahr

2013

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with limited therapeutic options. Clinical trials of several drugs which were shown to be effective in the superoxide dismutase (SOD1) model of ALS have shown null or negative effects when tested in humans. Here we discuss the role of pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, which failed to show efficacy in a recently published phase II clinical trial of ALS patients. The anti-oxidant and anti-inflammatory properties of pioglitazone make it an attractive therapeutic candidate for neurodegenerative disorders. However, its anti-diabetic and anti-dyslipidemic effects might be detrimental, as emerging evidence suggests that some features of the metabolic syndrome maybe protective in ALS. A number of clinical studies show that dyslipidemia, and high body mass index are associated with better clinical outcomes in ALS. This is further corroborated by studies on transgenic animal models and immortalized neuronal cell lines. Finally, the intricate interplay between glucose/lipid metabolism and susceptibility to oxidative damage in neurons warrants a judicious approach in further trials of anti-diabetic drugs in ALS.