Beata M. Wolska, PhD

Pak1 as a Target for New Treatment of Hypertrophic Cardiomyopathy
University of Illinois, Chicago, IL
Beata M. Wolska, PhD – $50,000

There is a general lack of specific treatments for patients with familial hypertrophic (HCM) or dilated (DCM) cardiomyopathies caused by mutations in myofilament proteins, the molecular machine responsible for ejection of blood from the heart. HCM, in which the heart's cells grow in size and remodel inappropriately, is the major cause of sudden cardiac death (SCD) in young people and athletes. Often, SCD is the first manifestation of HCM. Current therapies aim only to alleviate symptoms once manifestation of the disease is recognized, which is commonly during later stages of disease progression. Based on family history and genetic screening, HCM and DCM linked to mutations in myofilament proteins can be detected early and therapy could be started before the development of the disease or shortly after the first symptoms start to develop. This study hypothesizes that timely activation of an enzyme called p21-activated kinase (Pak1) can serve as a new therapeutic tool to delay and/or reverse the development of HCM. By choosing different starting time points of treatment it can be determined what is the critical point in the development of the disease for treatments to be successful. The long-term objective of the proposed study is develop new or modified therapies for treatment of genetically-linked cardiomyopathies. The goal is to take advantage of early childhood diagnosis and to start preventative therapy before the disease develops or shortly after it starts.