Clinton Smith, Ph.D. candidate in the Lewis Lab, received a National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke (NINDS) F31 Individual Predoctoral Fellowship for his project titled “Cryptococcal nanotherapy: Engineering a novel fungus-based platform for improved drug delivery to the central nervous system.”
The prestigious fellowship provides tuition, stipend and educational support, enabling Smith to advance his innovative research under the mentorship of Dr. Jamal Lewis, associate professor and BME graduate coordinator in the J. Crayton Pruitt Family Department of Biomedical Engineering. His project aims to develop a unique drug delivery platform that uses the neurotropic fungus Cryptococcus neoformans to transport therapeutics across the brain’s protective barriers, with the goal of improving treatment for amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases.
Neurodegenerative diseases affect more than 1.2 billion people worldwide, yet existing Food and Drug Administration–approved treatments, such as riluzole and edaravone for ALS, have limited impact on slowing disease progression. Resveratrol, a natural compound with neuroprotective properties, has shown promise in preclinical studies but faces challenges in reaching the central nervous system (CNS) due to physiological barriers and rapid clearance by the body.
To overcome these challenges, Smith’s work proposes engineering fungal drug carriers (FDCs) that can effectively bypass CNS barriers, protect resveratrol from premature degradation and deliver it directly to the brain. Cryptococcus neoformans is uniquely equipped for this role, leveraging multiple transport mechanisms and a survival process called vomocytosis to penetrate the CNS.
Smith’s research will focus on optimizing fungal drug carriers in vitro and then evaluating their biodistribution, bioavailability and therapeutic efficacy in preclinical ALS models. If successful, this approach could not only enhance treatment for ALS but also open the door to improved therapies for a broad range of neurodegenerative diseases.