Treatment of Dementia With Bosutinib: An Open-Label Study of a Tyrosine Kinase Inhibitor

Kennedy D Mahdavi; Sheldon E Jordan; Hannah R Barrows; Maša Pravdic; Barshen Habelhah; Natalie E Evans; Robin B Blades; Jessica J Iovine; Sergio A Becerra; Rachel A Steiner; Marisa Chang; Santosh Kesari; Alexander Bystritsky; Ed O'Connor; Hyman Gross; F Scott Pereles; Mike Whitney; Taylor Kuhn

doi:10.1212/CPJ.0000000000000918

Treatment of Dementia With Bosutinib: An Open-Label Study of a Tyrosine Kinase Inhibitor

Neurol Clin Pract. 2021 Jun;11(3):e294-e302. doi: 10.1212/CPJ.0000000000000918.

Authors

Kennedy D Mahdavi¹, Sheldon E Jordan¹, Hannah R Barrows¹, Maša Pravdic¹, Barshen Habelhah¹, Natalie E Evans¹, Robin B Blades¹, Jessica J Iovine¹, Sergio A Becerra¹, Rachel A Steiner¹, Marisa Chang¹, Santosh Kesari¹, Alexander Bystritsky¹, Ed O'Connor¹, Hyman Gross¹, F Scott Pereles¹, Mike Whitney¹, Taylor Kuhn¹

Affiliation

¹ Neurological Associates - The Interventional Group (KDM, MP, BH, NEE, RBB, JJI, RAS, MC), Santa Monica, CA; Department of Neurology (SEJ), University of California, Los Angeles; Neurological Associates of West Los Angeles (HRB, EOC), Santa Monica, CA; Synaptec Network (SAB), Santa Monica, CA; Pacific Neuroscience Institute (SK), Santa Monica, CA; Department of Psychiatry and Biobehavioral Sciences (AB, TK) University of California, Los Angeles; Department of Neurology (HG), University of Southern California, Los Angeles; and Rad Alliance, Inc. (FSP, MW), Los Angeles, CA.

Abstract

Objective: The pursuit of an effective therapeutic intervention for dementia has inspired interest in the class of medications known as tyrosine kinase inhibitors such as bosutinib.

Methods: Thirty-one patients with probable Alzheimer dementia or Parkinson 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.

Results: The present article 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 (M_age = 73.7 years, SD_age = 14 years). Bosutinib was associated with less worsening in Clinical Dementia Rating (CDR) scores (hazard ratio = -0.62, p < 0.001, 95% confidence interval [CI]: -1.02 to -0.30) and less decline in RBANS performance (hazard ratio = -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 postintervention, 31.2% of participants exhibited worsened CDR levels compared with their 12-month performances.

Conclusions: Results 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.