Results out on the NILO-PD trial of Nilotinib
 

Results of the NILO-PD (Northwestern University) phase 2 trial of Nilotinib show the drug to be safe & tolerable. Unfortunately, it did not demonstrate any benefit for Parkinson's symptoms or biological measures. Basically, it doesn't have very good BBB penetration. Trials will begin on several other c-Abl inhibitors which appear to have better brain penetration.

There will be a webinar on Dec. 17th where more detail will be provided and questions answered.

Though safe, nilotinib does not show promise for benefit for Parkinson's disease

curcumin
 

I am disappointed, again, that another clinical trial seems to have failed. Curcumin does seem to have an effect on a-aynuclein. It's easy to buy and should be safe.





Curcumin Treatment Improves Motor Behavior in α-Synuclein Transgenic Mice



The curry spice curcumin plays a protective role in mouse models of neurodegenerative diseases, and can also directly modulate aggregation of α-synuclein protein in vitro, yet no studies have described the interaction of curcumin and α-synuclein in genetic synucleinopathy mouse models. Here we examined the effect of chronic and acute curcumin treatment in the Syn-GFP mouse line, which overexpresses wild-type human α-synuclein protein. We discovered that curcumin diet intervention significantly improved gait impairments and resulted in an increase in phosphorylated forms of α-synuclein at cortical presynaptic terminals. Acute curcumin treatment also caused an increase in phosphorylated α-synuclein in terminals, but had no direct effect on α-synuclein aggregation, as measured by in vivo multiphoton imaging and Proteinase-K digestion. Using LC-MS/MS, we detected ~5 ng/mL and ~12 ng/mL free curcumin in the plasma of chronic or acutely treated mice, with a glucuronidation rate of 94% and 97%, respectively. Despite the low plasma levels and extensive metabolism of curcumin, these results show that dietary curcumin intervention correlates with significant behavioral and molecular changes in a genetic synucleinopathy mouse model that mimics human disease.

Georgetown has reported the results of their Nilotinib clinical trial. They may interpret the data differently, however, the results really are quite similar to the Northwestern trial. I believe they are hopping to get support for a phase 3. I honestly think, though, that given the limited amount of research dollars available, the funds would be better used to research the other three c-abl inhibitors that are going into trial. They all have better neurological profiles than nilotinib.

Nilotinib Effects on Safety, Tolerability, and Potential Biomarkers in Parkinson Disease: A Phase 2 Randomized Clinical Trial | Movement Disorders | JAMA Neurology | JAMA Network