Treatment of Dementia With Bosutinib

Abstract

ObjectiveThe pursuit of an effective therapeutic intervention for dementia has inspired interest in the class of medications known as tyrosine kinase inhibitors such as bosutinib.MethodsThirty-one patients with probable Alzheimer's dementia or Parkinson's spectrum disorder with dementia completed 12 months of bosutinib therapy and an additional 12-months of follow-up. The Clinical Dementia Rating scale (as estimated by the Quick Dementia Rating System [QDRS]) was the primary cognitive status outcome measure. Secondary outcome measures included the Repeatable Battery Assessment of Neuropsychological Status (RBANS) and the Montreal Cognitive Assessment. Cox regression methods were used to compare results with population-based estimates of cognitive decline.ResultsThe present paper reports on cognitive outcomes obtained at 12 months for 31 participants and up to 24 months for a 16-participant subset. Safety and tolerability of bosutinib were confirmed among the study population (Mage = 73.7 years, SDage = 14 years). Bosutinib was associated with less worsening in Clinical Dementia Rating (CDR) scores (HR = −0.62, p < 0.001, 95% confidence interval [CI]: −1.02 to −0.30) and less decline in RBANS performance (HR = −3.42, p < 0.001, 95% CI: −3.59 to −3.72) during the year of treatment than population-based estimates of decline. In the 24-month follow up, wherein 16 patients were observed after 1 year post-intervention, 31.2% of participants exhibited worsened CDR levels compared to their 12-month performances.ConclusionsResults support an overall positive outcome after 1 year of bosutinib. Future studies should explore the relationship between tyrosine kinases and neurodegenerative pathology as well as related avenues of treatment.

Insights into the management of Lewy body dementia: a scoping review

“…Bosutinib, an Abl tyrosine kinase inhibitor, was found to be safe and well-tolerated with reported side effects limited to upset stomach, fatigue, and diarrhea, In an open-label phase 1 study of 31 participants with AD or PDD, four participants left the study for personal reasons, in exploratory analyses, there was less decline on the Quick Dementia Rating System (QDRS) and the Repeatable Battery Assessment of Neuropsychological Status at 12 months in those on treatment compared with population-based estimates of decline 84 . In a subsequent 12-week phase two study of 25 men and only one woman with DLB, there were no serious adverse events or dropouts and investigators noted a dose-dependent increase of bosutinib in plasma and CSF (100–400 mg per dose) 71 .…”

Dementia with Lewy Bodies Drug Therapies in Clinical Trials: Systematic Review up to 2022

“…Nilotinib is approved by the FDA for treatment of chronic myeloid leukemia, but has failed to demonstrate benefit in phase 2 trials in PD, PDD, and AD [11]. Bosutinib, another tyrosine kinase inhibitor approved for chronic myeloid leukemia, was associated with less worsening in CDR-SB and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) performance in an open label study with 15 AD and 16 PDD patients after 1 year of treatment [18]. A phase 2 clinical trial was recently completed in DLB showing adequate safety and tolerability, reduction of CSF a-synuclein and dopamine catabolism, and functional improvement in activities of daily living [19].…”