Could a Pfizer Cancer Drug be a Treatment for a Form of Dementia? Georgetown University Launches Clinical Trial to Find Out

Dementia Treatment TrialsiteN

Georgetown University Medical Center recently launched the only known therapeutic (disease modifying) clinical trial for Lewy body dementia, a neurological disorder afflicting millions in the United States. There are no approved medications that modify this disease. Based on years of preclinical research, the team is investigating whether a Pfizer cancer drug (bosutinib) can be repurposed and used to treat Lewy body dementia.

Preclinical Research

Alpha-synuclein accumulation can cause the loss of dopamine, which controls movement, emotions, attention and other cognitive functions. Other proteins, beta-amyloid and tau, are also thought to contribute to the disease (Lewy body dementia).

Preclinical animal studies have show that bosutinib can lower the levels of alpha-synuclein, tau and beta-amyloid; reverse the loss of dopamine; and reduce inflammation in the brain. These animal studies have revealed that bosutinib may be able to decrease inflammation and reverse dopamine loss at lower doses than what is used for leukemia. Bosutinib is the second investigational drug development by Georgetown Translational Neurotherapeutics Program (TNP) to be validated in animal studies and advance, via approved Investigator New Drug (IND) application, to clinical trials.

Charbel Moussa, MBBS, PhD, clinical and scientific research director of the TNP and director of Laboratory of Dementia and Parkinsonism said, “We have been studying bosutinib for almost a decade as a potential therapy to modify neurodegenerative pathologies, including Lewy body dementia.” The laboratory director continued, “In animal models, bosutinib ameliorates neurodegenerative pathologies and behavior at much lower doses than the cancer dose, providing strong feasibility to study this drug in individuals with LBD.”

The Study: Repurposing Pfizer’s Leukemia Drug Bosulif®

Now, the Georgetown University investigators are assessing bosutinib (Bosulif®) which has been approved by the FDA to treat a form of leukemia but no other uses.

Based on the previously mentioned preclinical research from the Laboratory of Dementia and Parkinsonism at Georgetown University Medical Center, a Lewy Body Dementia Association “Research Center of Excellence,” investigators now have developed the foundational hypothesis for the utilization of an approved cancer drug.

A Phase II, randomized double-blind, placebo controlled clinical trial, some of the patients will be randomly selected via IXRS (interactive response system)  to receive the active drug (bosutinib) or the placebo. Double blinded means that neither the patient nor the health care providers will be known whether the study participant is taking the active drug or the placebo.  Participants must have a study partner to accompany them to clinic visits. The investigator-initiated trial will enroll 30 patients.

Principal investigator Fernando Pagan, MD noted that treatment for Lewy body dementia, the second most common cause of dementia is desperately needed. Pagan commented, “Lewy body dementia is often confused with Alzheimer’s or Parkinson’s disease.”

Lead Research/Investigator

Fernando Pagan, Medical Director, Georgetown Translational Neurotherapeutics Program and director  of the Movement Disorders Clinic at MedStar Georgetown University Hospital