08/25/2020
New NIH Grant to Study Aging-Related Disorders in People with HIV
Asha Kallianpur, MD, MPH, Genomic Medicine Institute, has received a two-year, $161,000 grant from the National Institutes of Health to investigate the role of an iron-binding protein in the development of chronic, aging-related diseases in people with HIV (PWH).
With highly effective antiretroviral therapy, the risk of developing AIDS-defining illnesses has greatly decreased and survival among treated PWH is now close to normal. However, these individuals experience an unusually high and premature risk of degenerative, aging-related conditions that negatively impact their functional status and quality of life.
Chronic kidney disease (CKD) and cognitive impairment are two such conditions that often co-occur in PWH, causing increased frailty and death, and they may share a common mechanism. Non-invasive biomarkers of CKD and cognitive decline are urgently needed to identify PWH who are at high risk and to inform new preventive and treatment interventions for these and other aging-related disorders.
Dr. Kallianpur and her team previously discovered that a specific form of ferritin, the important antioxidant protein that stores and delivers iron, may play a significant role in the development of both CKD and cognitive impairment. Specifically, they found that cerebrospinal fluid levels of a ferritin subunit (a single protein molecule, which assembles with other types of ferritin subunits to form intact ferritin) predicts neurocognitive function in PWH. They also identified a potential link between this ferritin subunit and CKD in PWH, finding that the receptor for the subunit also serves as an early marker of kidney damage.
With this new award, the researchers will investigate whether an HIV-related shift in the ratio of ferritin subunits may explain the higher risk of aging-related disorders in PWH. Harnessing existing data and samples from a large, multi-center HIV cohort study, they will evaluate cross-sectional and longitudinal associations between measured levels of the ferritin subunit (and its receptor) and development of CKD, cognitive impairment and frailty.
"We hope that the results from this initial study will provide proof-of-concept that aging-related conditions in PWH share at least one underlying mechanism. The study could also highlight new, non-invasive biomarkers for kidney disease and cognitive decline for us to test prospectively in larger studies," Dr. Kallianpur said. "If ferritin imbalance proves to be a novel mechanism for increased aging and degenerative disorders in this population, we can use that knowledge to develop new therapies and improve clinical care."
Dr. Kallianpur received a January 2020 Caregiver Catalyst Grant for this work.
