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12-05-2019, 07:40 PM | #1 | ||
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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 |
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12-11-2019, 01:28 PM | #2 | ||
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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. |
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12-16-2019, 02:05 PM | #3 | ||
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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 |
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"Thanks for this!" says: | jeffreyn (12-16-2019), soccertese (12-17-2019) |
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