Investigator:
Helen Hwang, MD, PhD
Name of Institution:
Washington University School of Medicine
Project Title:
Characterization of inhibitors of alpha-synuclein fibril growth
Investigator Bio:
Dr. Hwang is a Movement Disorder Neurologist and an Instructor at Washington University School of Medicine. She obtained her BA and BS degrees in Psychology and Bioengineering from the University of California, San Diego. Following this, she matriculated at the MD/PhD program at the University of Illinois in Urbana, IL where she studied telomere biology with single molecule fluorescence under the mentorship of Dr. Sua Myong. Dr. Hwang then completed her Neurology and Movement Disorder training at Washington University in St Louis. During her fellowship, she became interested in potential biomarkers and therapeutics for Parkinson’s disease (PD). She has developed an in-vitro fluorescence platform of alpha-synuclein (a-syn) fibril growth for screening small molecules for potential therapeutics for PD and is interested in expanding this work into a cellular model.
Objective:
To create a cell-based platform to test potential drug candidates for the ability to inhibit a-syn fibril growth, a process thought to contribute to PD progression. .
Background:
PD is believed to be due to accumulation of a-syn in the substantia nigra and other brain regions. Pathology studies suggest that disease severity, as measured by disease duration and degree of cognitive impairment, is related to a-syn fibril concentrations in brain regions. I hypothesize that a-syn fibril accumulation contributes to PD progression and this process can be targeted by small molecule inhibitors of fibril growth.
Methods/Design:
In this study, I will optimize an a-syn fibril-sensitive immunoassay by testing a variety of antibodies and comparing their sensitivity to our current assay. We will then develop cell-based platforms to test existing lead compounds to see whether they can prevent the accumulation of a-syn fibrils.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
A cellular platform for testing potential drug compounds that can have disease-modifying effects in patients with PD can then be used to screen for small molecules capable of inhibiting a-syn fibril growth. This tool will hopefully bring us closer to identifying potential neuroprotective agents for PD.