Doug Feinstein, Ph.D. (Professor, Anesthesiology; Bioengineering; Cell Biology and Anatomy; Biopharmaceutical Science) studies novel approaches to reduce damage and inflammation in neurodegenerative diseases. Studies include analysis of disease progression in mouse models of Alzheimer’s disease (AD) and multiple sclerosis (MS), in vitro studies using primary cultures of neurons and glial cells from wild type and transgenic mice, and analysis of the molecular events involved. Dr. Feinstein is involved in the design of early stage clinical trials for MS and AD. Lastly, investigations on the effect of volatile anesthetics on neuro-inflammation are in progress.
Project 1. Dr Feinstein pioneered discoveries showing that neurons in the brain that synthesize the neurotransmitter noradrenaline are damaged in AD patients, and this contributes to AD pathology (9, 15). Projects in the lab are characterizing when and how this damage occurs, and use novel drugs to reduce that damage. These treatments include treating mice with droxidopa, a compound similar to the Parkinson’s drug levodopa, but which is converted to noradrenaline rather than dopamine.
Project 2 is screening a panel of novel compounds for the ability to induce immature neurons to differentiate into mature noradrenergic neurons. There are 2 ongoing projects that test treatments to reduce disease in EAE, the animal model of MS. The first trial involves studies on a compound called dimethyl fumarate (DMF), which is in phase III trials for MS although the mechanism(s) of action are not known. Dr Feinstein showed that DMF reduces inflammation in the brain, and recently reported that DMF increases the number of T regulatory cells that reduce CNS inflammation. Studies are aimed to determine how DMF acts on these Tcells. The 2nd MS project is based on recent findings that the inhaled anesthetic, sevoflurane, reduces EAE disease, and may also involve effects on Tregs.