A new company with Brown roots bets on neurogenesis to treat central nervous system diseases.
A biotech startup that’s trying to accelerate the formation of new neurons to treat brain conditions says it is making significant progress.
Bolden Therapeutics, cofounded by a Brown medical student and two faculty members, has secured more than $1 million in private and public funding, including grants from the National Institutes of Health, and earned Brown’s 2022 Startup of the Year Award.
The company aims to use an RNA-based therapy to increase neurogenesis and thereby improve outcomes in neurological conditions. Enhancing neuron formation could provide novel means of treating neurodegenerative disorders, depression, traumatic brain injury, stroke, and other conditions.
“Our goal for now is to translate exciting research on novel biology from Brown and gain enough support to develop the safest, most effective candidate possible,” cofounder and CEO Johnny Page ’18 ScM’19 MD’25 says—with the ultimate goal of enabling better treatment options for patients.
Bolden represents the fusion of research from the labs of its scientific founders: Justin Fallon, PhD, professor of medical science and of psychiatry and human behavior; and Ashley Webb, PhD, the Richard and Edna Salomon Assistant Professor of Molecular Biology, Cell Biology, and Biochemistry.
Fallon, who’s also chair of Bolden’s scientific advisory board, has studied a molecular signaling pathway in muscle involving bone morphogenetic protein (BMP) for several years. After he heard Webb present on how blocking BMP signaling can drive neurogenesis by allowing stem cells to divide, they teamed up to understand the role of the pathway in neural stem cells.
The pair found that genetic manipulation of this pathway in mice led to increased neuronal growth and improved cognitive function. Recognizing the therapeutic potential of the intervention, the researchers formed Bolden.
“One of my favorite things about Bolden is working with a small group of people with complementary expertise to tackle a problem together,” says Webb, a member of the scientific advisory board.
The team is focusing on antisense oligonucleotides, or ASOs, which are RNA-based therapies already on the market for conditions like spinal muscular atrophy. Page says the development of ASOs is relatively well understood, inexpensive, and rapid compared to that of other treatment methods. Bolden designed ASOs to remove only one offending component of a protein in the signaling pathway, leaving the protein’s structure and complementary functions otherwise intact, Fallon says.
“To have several [drug]candidates that achieve the desired effect on RNA in cells is an extremely exciting position to be in,” Page says.
Bolden is conducting preclinical trials with their ASOs to optimize the drug candidates, identify an initial clinical application, and eventually file for an FDA Investigational New Drug designation.
Alzheimer’s disease is one condition the company may target, given its severity and limited treatment options. For such complex, multifactorial illnesses, the therapy would likely be used in combination with other treatments, says Stephen Salloway, MD, MS, the associate director of Brown’s Center for Alzheimer’s Disease Research.
For Bolden, “the ultimate goal is to replenish new neurons in the context of disease,” Webb says. “Even if it only helps with one disease, we hope to improve the lives of patients.”