**5.3.59 Physostigmine**

The acetylcholine esterase inhibitor physostigmine did not show a benefit in ALS patients (Norris et al., 1993).

### **5.3.60 Pioglitazone**

Pioglitazone activates the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ) (Gillies & Dunn, 2000; Kiaei, 2008). It has been used as anti-diabetic drug in diabetes type 2.

In phase II clinical trial (NCT00690118), pioglitazone was found to be save and welltolerated, but showed no effect on ALS disease progression (Ludolph et al., 2010).

In a riluzole add-on phase II study (NCT00919555), pioglitazone is currently evaluated in combination with tretinoin.
