Stephen Gomperts (United States of America)
Massachusetts General Hospital
Neurology
Stephen Gomperts, MD, PhD is an Assistant Professor of Neurology at Massachusetts General Hospital and Harvard Medical School. He attended medical school and graduate school in Neuroscience at the University of California, San Francisco before completing his Neurology residency in the Harvard Program at the Massachusetts General Hospital (MGH) and Brigham and Women's Hospital, a research fellowship at the Massachusetts Institute of Technology, and clinical fellowships in Movement Disorders and Memory Disorders at MGH. He is the founding Director of the MGH Lewy Body Dementia Unit, a Lewy Body Dementia Association Research Center of Excellence. His translational and clinical research program for Parkinson’s disease, dementia with Lewy bodies, and Alzheimer’s disease uses laboratory models of disease, neurophysiology, and human molecular imaging to advance understanding, improve diagnosis, and develop and evaluate novel therapeutic strategies for these neurodegenerative diseases.

Moderator of 1 Session

 Conference Calendar
SYMPOSIUM

ALPHA-SYNUCLEIN, PD ANIMAL MODELS, MECHANISTIC ASPECTS AND THERAPEUTIC STRATEGIES

Session Type
SYMPOSIUM
Date
Fri, 18.03.2022
Session Time
05:15 PM - 06:45 PM
Room
ONSITE: 113
Chair(s)

Presenter of 1 Presentation

 Conference Calendar

CARBON MONOXIDE AT LOW DOSES REDUCES DOPAMINE CELL LOSS AND ALPHA-SYNUCLEIN PATHOLOGY IN MODELS OF PARKINSON’S DISEASE

Session Name
1320 - ALPHA-SYNUCLEIN, PD ANIMAL MODELS, MECHANISTIC ASPECTS AND THERAPEUTIC STRATEGIES (ID 218)
Session Type
SYMPOSIUM
Date
Fri, 18.03.2022
Session Time
05:15 PM - 06:45 PM
Room
ONSITE: 113
Lecture Time
06:15 PM - 06:30 PM
Presenter

Abstract

Abstract Body

Aims: Exposure to low doses of carbon monoxide (CO) may underlie the reduced risk of Parkinson’s disease (PD) among smokers. Here, we set out to evaluate the neuroprotective potential of low-dose CO treatment in PD models.

Methods: In the AAV-alpha-synuclein (aSyn) model, rats underwent right nigral injection of AAV1/2- asynA53T and left injection of empty AAV, and were treated with oral CO drug product (HBI-002 10ml/kg, daily by gavage) or vehicle. HBI-002 is under development by Hillhurst Pharmaceuticals. In the short-term MPTP model (40mg/kg, i.p.), mice were treated with inhaled CO (iCO) (250ppm) or air. HPLC measurement of striatal dopamine, immunohistochemistry for nigral aSyn and tyrosine hydroxylase, stereological cell counting, and biochemical analyses were conducted blinded to treatment condition.

Results: Each HBI-002 treatment increased carboxy-hemoglobin to 6%. Administration of HBI-002 in the aSyn model reduced ipsilateral loss of both striatal dopamine and TH-positive neurons in the substantia nigra pars compacta compared to rats treated with HBI-002 vehicle. HBI-002 reduced aSyn aggregates and S129 phosphorylation. MPTP-exposed mice treated with low dose iCO had higher dopamine levels and more TH+ neurons than those treated with air. In saline-treated mice, iCO had no effect on striatal dopamine levels or TH+ cell counts. HBI-002 upregulated heme oxygenase-1 and HIF-1α.

Conclusions: These results demonstrating reduced dopamine cell death and aSyn pathology advance low dose CO as a potential neuroprotective strategy for PD.

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