Research at the University of Denver is showing promise for the treatment of neurodegenerative conditions such as Parkinson’s disease and Alzheimer’s disease. Sunil Kumar, Ph.D., assistant professor of chemistry and biochemistry at DU and its Knoebel Institute for Healthy Aging, is leading the research.
Kumar received his doctorate from Clemson University and did postdoctoral work at Yale University and New York University before establishing the Kumar Lab at DU in 2019. “My training in my graduate study and my postdocs is mostly in organic synthesis, where we develop small molecule strategies and target different proteins,” he said. “My research program was built on high-throughput platform technology we developed for small molecule ligands. We call them synthetic protein mimetics, or artificial proteins.”
The lab has been able to accelerate the development of such molecules with innovative technology. “The platform technology means they contain a larger library of these molecules with a lot of chemical diversities on them, and then we target pathological proteins,” Kumar said.
The lab started by targeting the alpha-synuclein protein, which is heavily expressed in neurons in the brain, and have since advanced to test synthetic molecules on mice. The clumping of alpha-synuclein occurs with the onset of Parkinson’s disease, but that can be mitigated by artificial proteins with certain properties, Kumar said.
“It [alpha-synuclein] helps in regulating the release of dopamine, which is a neurotransmitter, so that we can regulate our motor functions,” he explained. “When it aggregates, it starts clumping together, and then it impairs the function of neurons and stops the release of dopamine.”
Kumar said the platform helped develop “very potent compounds” that mimic a protein’s surface. “We can synthetically tune the [chemical diversities] and put them on their surface so that when they bind to the protein surface, they can achieve the maximum interaction, and that decreases the side effects,” he said. “If you do not have chemical diversity, they will not be very specific to the target. You need a lot of chemical diversity, and to bring the chemical diversity on those scaffolds, they need to be redesigned.”
The team has also seen opportunities to apply its synthetic protein molecules to other diseases, including Alzheimer’s.
“There is a target called tau protein that also clumps and impairs the function of a separate kind of neurons,” Kumar said. “We’ve also used this platform technology for ALS [amyotrophic lateral sclerosis] disease, where there’s a protein called TDP-43, and we got some really fantastic data.”
Kumar said the artificial proteins developed by his lab are able to cross the blood-brain barrier at about 20 times the rate of antibody-based treatments that are currently on the market for neurodegenerative conditions.
“Because they target these diseases that happen in the brain, if they can’t cross the barrier, that’s a problem,” he said. “That’s where our molecules very much outweigh other strategies, like antibody-based strategies, because antibodies have always struggled to cross the blood-brain barrier because of their big size.”
The ability of the proteins to cross the blood-brain barrier theoretically “decreases the side effects and increases the potency of the drug in the brain” in comparison with antibody treatments, he added.
Kumar said his research was nascent when the COVID-19 pandemic hit, but the lab was “continuously making progress” and started to make waves in the broader research community. “While we were collecting this data, one great thing that happened is we got a lot of attention,” he said.
A lot of that attention was catalyzed by publications in scientific journals. Nature Communications has published three papers by Kumar, and he expects Science Translational Medicine to publish a major study later in 2025. “That’s the biggest paper of my life, and probably DU’s as well,” Kumar said.
“We are building our reputation and our work is very, very critical,” Kumar said. “I’m really appreciative of my team. When we sent our first paper to Nature Communication, I was a little scared that I didn’t have a reputation, I didn’t have a name, and then it went through, and then the second went through, and the third went through, so that gives us a lot of confidence.”
That attention has coincided with major growth for the Kumar Lab. When Kumar launched his lab at DU six years ago, it had about $500,000 in funding and three graduate students working at it. Now it has more than $4 million in funding and 18 students. The lab has won funding from the American Parkinson’s Disease Association, the Parkinson’s Foundation, the U.S. Department of Defense and the National Institutes of Health.
Within DU, Kumar is likewise winning accolades for his lab’s accomplishments. “The prevalence of neurodegenerative disease has been on the rise over the past several decades and is expected to double again over the next 20 years, making the development of this invention into a publicly available treatment — through partnership with a clinically experienced startup and his co-inventors — an outstanding success for DU and KIHA,” said Dr. Corinne Lengsfeld, DU’s senior vice provost for research and graduate education. “DU is so proud and excited for Sunil and his team.”
Kumar has teamed with Denver-based Dr. Rajeev Kumar (no relation) of the Rocky Mountain Movement Disorders Clinic to co-found Neurofold Therapeutics Inc. in 2024. The startup is licensing the patents from DU to commercialize the Kumar Lab’s research.
“I started looking at what he was doing and looking at his basic data and his animal model data, and more recently, his mouse model data, which is really quite spectacular,” said Dr. Rajeev Kumar. “We chatted, and we said, ‘Okay, let’s plan on seeing how I can help you, and if we can form a company to try to commercialize these discoveries.’”
The Kumar Lab is now moving toward human clinical trials that will be conducted in conjunction with Neurofold The first one will study the molecules on Parkinson’s and Lewy Body Dementia, followed by ALS and tau-related Alzheimer’s disease.
Neurofold has landed some seed funding, but the company will soon attempt to raise funds to support the clinical trials, said Dr. Rajeev Kumar. “We’re planning on raising additional outside capital to accelerate the development of these molecules and the drug discovery platform that Sunil has,” he explained. “We’re pretty excited.”
