Michael Placzek, PhD

Instructor at Massachusetts General Hospital, Jacob Hooker, PhD

COX-2 PET radiotracers for imaging early HD pathology in the living brain

To develop effective therapeutics for Huntington’s Disease (HD), we need to understand biological changes in the living brain that occur at the earliest evidence of disease conversion. Imaging with positron emission tomography (PET) allows researchers and clinicians to measure how critical targets, such as proteins or enzymes, change in the living brain, at disease onset and throughout disease progression. More importantly, PET can measure how a target changes following therapeutic intervention, a critical step in assessing treatment efficacy. The study of these critical targets with PET requires specific molecules tagged with a radiolabel (radioligands). Although many radioligands have been developed over the years for PET and neurodegenerative disease, no PET ligands have been able to predict disease conversion or aid prognosis in HD. Therefore, it is imperative that we develop new PET radioligands that allow us to monitor important molecular changes in the living brain of HD patients. Our studies show that a particular protein, cyclooxygenase-2 (COX-2), is dramatically altered in the HD brain, even in premanifest HD. Our data indicates COX-2 holds promise as a novel clinical marker of HD onset and progression. We will develop COX-2 selective PET radiotracers that will enable the study of disease mechanisms in the living HD brain. We believe this research will provide an objective clinical marker that can assess, and lead to the discovery of, effective disease-modifying therapeutics for HD patients.