Investigator:
Abby Olsen, MD, PhD
Name of Institution:
University of Pittsburgh
Project Title:
Validating Ak1 as a Therapeutic Target in a Mammalian Parkinson’s Disease Model
Investigator Bio:
Dr. Abby Olsen is an Assistant Professor of Neurology at the University of Pittsburgh and the University of Pittsburgh Medical Center. She is a graduate of Carleton College in Northfield, MN, and completed her MD/PhD at the University of Pennsylvania, followed by a residency in neurology and fellowship training in movement disorders at Massachusetts General Hospital/Brigham and Women’s Hospital.
Dr. Olsen received the NINDS K08 award, a Department of Defense Parkinson’s Disease Early Investigator Award, as well as the American Parkinson Disease Association’s George C. Cotzias Fellowship. Her research utilizes a combination of Drosophila (fruit fly) and human genetics to identify novel glial genes that contribute to the pathogenesis of Parkinson’s disease (PD) and other alpha-synucleinopathies, with the long-term goal of developing glial-based therapeutics for alpha-synucleinopathies. Additionally, she studies gene-environment interactions that contribute to PD. She has successfully transitioned to independence, moving from Brigham and Women’s Hospital in Boston to her own laboratory at the University of Pittsburgh in 2022. Dr. Olsen also cares for patients with PD and atypical parkinsonism, and she is the Director of a Multiple System Atrophy Center of Excellence at the University of Pittsburgh Medical Center.
Objectives/Background:
The goal of our research is to develop new treatments for PD by turning to cell types that have been previously overlooked, called glia. Glia are the brain’s helper cells that support the neurons. To study glia, we use a fruit fly model that mimics the key features of human PD. In the glia, we can measure the effect of any gene on abnormal movement. This allows us to identify glial genes that improve movement in the fly, which are potential therapeutic targets for PD. One gene that we identified in the fly is called adenylate kinase 1 (Ak1). When we reduce expression of Ak1 in glia, movement is improved. The goal of this proposal is to test this same gene in mice. If it works the same way in mice as it does in the fruit fly, then it will be a good candidate for testing in people with PD.
Methods/Design:
Our work in the fruit fly shows that when we reduce expression of Ak1, there is improvement in movement. The goal of this proposal is to determine whether that is also true in mice. First, we will induce Parkinson’s-like symptoms in mice that are genetically engineered to lack the Ak1 gene. The hypothesis is that these mice will be relatively resistant to traditional Parkinson’s symptoms compared to normal mice. Next, we will determine in which cell types and brain regions Ak1 is expressed. This will give us a better idea of where and how the gene acts to worsen PD. It will help us decide whether we can give an oral drug to reduce Ak1 activity everywhere or whether we need to use a biological drug to target it in specific cells.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
This work will validate Ak1 as a therapeutic target in mice. If successful, we will use the information learned here to design a specific drug to inhibit Ak1, which can then be tested in additional models, including non-human primates, and eventually in first-in-human studies. Our work indicates that Ak1 is a disease-modifying therapy, rather than a symptomatic therapy, meaning that it could be the first ever therapy that slows down progression of PD rather than simply helping with the symptoms.