Nilotinib may be an inappropriate candidate
The data “suggest that the hypothesis wasn’t tested, since the CSF and serum concentration of the drug were insufficient for enzyme inhibition,” said Peter LeWitt, MD, Sastry Foundation Endowed Chair in Neurology and professor of neurology at Wayne State University, Detroit. “A higher dose or a more CNS-penetrant drug would be needed for adequate testing of the hypothesis that c-Abl inhibition could provide disease modification.”
Nilotinib might not be an appropriate drug for this investigation, he continued. “There may be better choices among c-Abl inhibitors for penetration into the CNS, such as dasatinib, or for increased potency of effect, such as imatinib.”
Sun Pharma Advanced Research Company is conducting a clinical trial of KO706, another c-Abl inhibitor, added Dr. LeWitt, who is a researcher in that trial and an editorial adviser to Neurology Reviews. “The studies published recently in JAMA Neurology by Pagan et al. claiming target engagement with nilotinib in Parkinson’s disease patients need to be contrasted with the results of the current investigation. Disease modification with c-Abl inhibition continues to be a promising therapeutic avenue, but both positive and negative study results need careful reassessment and validation.”
The Michael J. Fox Foundation, the Cure Parkinson’s Trust, and Van Andel Research Institute funded the study. Novartis provided the study drug and placebo. The investigators reported no conflicts of interest.
SOURCE: Simuni T et al. AAN 2020. Abstract 43617.