JAMA neurology: The efficacy of nilotini in patients with late-middle-aged Parkinson's

Parkinson's disease (PD) is the second most common neurodegenerative disease, affecting 1% of the population over the age of 65.
PD symptoms usually appear slowly over time, with the most obvious symptoms in the early stages of tremors, limb stiffness, decreased motor function, and gait abnormalities, and cognitive and behavioral problems in later stages.
addition, dementia is quite common in severe PD patients, with more than a third of cases also occurring with severe depressive disorder and anxiety.
the development of drugs is improving, the current drug still does not meet the need to slow the progress of PD.
Nilotinib, which inhibits BCR-Abl, has been approved for the treatment of chronic granulocytic leukemia.
but animal studies in recent years have found that nilotini is neuropulentive in PD animal models.
findings have sparked interest in developing nilotininis to slow PD progress.
, however, the safety and tolerance of Nilotini is still unknown.
previously, Nilotini's clinical experience in PD therapy had come from only a small study.
Subsequently, in 2020, the results of a Phase 2 clinical trial conducted by the same team were reported, showing that nilotine showed acceptable safety and tolerance in moderate late PD and improved PD biomarkers, but had no significant impact on clinical outcomes.
, a multi-center RCT study was conducted by Northwestern University and the NILO-PD International Research Group to assess nilotinib's safety and tolerance among participants.
the study was a six-month, multi-center, randomized parallel group, double-blind, placebo-controlled trial.
patient recruitment period is from 20 November 2017 to 28 December 2018 and the follow-up ends on 9 September 2019.
the study was conducted at 25 clinical centers in the United States.
the study initially screened 173 patients, 48 of whom declined and 125 were studied.
, 76 patients who received PD medication were admitted to the group.
participants were randomly treated with a placebo, 150 mg nitrotinib, or 300 mg nitrotinib at 1:1:1, once a day or oral for 6 months followed by a 2-month non-drug evaluation.
result is the safety and toerability of the drug.
secondary results include changes in PD disability (MDS-UPDRS score Part II OFF/ON).
results include serum and CSF pharmacodynamic characteristics, as well as CSF dopamine biomarkers.
the average baseline age of participants was 64.6 years and the average course of illness was 9.9 years.
MDS-UPDRS Part 1-3 OFF score is 66.4, ON score is 48.4 and Montreal Cognitive Assessment (MOCA) score is 27.1.
in placebo, 150 mg and 300 mg arm, the participants who received the specified dose completed the study at 21 (84%), 19 (76%) and 20 (77%), respectively, and the safety of both active doses was acceptable.
most common reasons for drug suspension are asymptomatic, dose-dependent amylase, and/or increased lipase.
in the first month, Nilotini 150 mg and 300 mg both showed worse MDS-UPDRS-3 ON scores than placebos.
but from baseline to 6 months, there was no difference in changes between groups of MDS-UPDRS-3 OFF.
concentration of cerebrospinal fluid/serum nitrotinie was 0.2% to 0.3%.
there is no evidence of changes associated with the treatment of dopamine metabolites in CSF.
Based on the above findings, the researchers believe that nilotinib has acceptable safety and tolerance, but low CSF exposure and lack of biomarker effects, coupled with negative efficacy data, suggest that nilotinib should not be further tested in PD.
reference: Simuni T, et al. Efficacy of Nilotinib in Patients With Moderately Advanced Parkinson Disease: A Randomized Clinical Trial. JAMA Neurol. 2020 Dec 14:e204725. doi: 10.1001/jamaneurol.2020.4725.MedSci Original Source: MedSci Original Copyright Notice: All noted on this website "Source: Met Medical" or "Source: MedSci Original" text, images and audio and video materials, copyrights are owned by Metz Medicine, without authorization, no media, website or individual may reproduce, authorized to reproduce with the words "Source: Mets Medicine".
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