An illustration of communication between nerve cells in the brain. Video: Jitendra Jadhav/Creatas Video+/Getty Images Plus
The Carol and Gene Ludwig Family Foundation has committed a new $2.7 million grant to continue the Ludwig Neurodegenerative Disease Seed Grants Program at Harvard Medical School, which was established with the foundation’s original grant in 2021. The initiative advances innovative, early-stage research into neurodegenerative diseases, particularly Alzheimer’s disease (AD).
Since its start, the program has provided seed funding for nine studies, with preference given to high-risk, high-reward, interdisciplinary projects with translational potential.
Established in 2002, the Carol and Gene Ludwig Family Foundation makes strategic charitable investments to support medical research, education, and community engagement. |
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“The initiative aims to support researchers who are approaching neurodegenerative disease from new perspectives and to foster a community of scientists on the HMS Quad who can work together to understand the mechanisms of neurodegeneration,” says Michael Greenberg, PhD, the Nathan Marsh Pusey Professor of Neurobiology in the Blavatnik Institute at HMS. He says the new grant is particularly timely because federal funding for biomedical research has become more uncertain, especially for early-stage projects.
Greenberg co-leads the program with Mark Namchuk, PhD, the Puja and Samir Kaul Professor of the Practice of Biomedical Innovation and Translation and the executive director of therapeutics translation at HMS. Namchuk says that in a disease area like AD, therapeutic progress will require the validation of new ideas and concepts. “This is a critical component of what the program is supporting,” he says.
Among the program’s most recent grant recipients are Bruce Bean, AB ’73, PhD, the Robert Winthrop Professor of Neurobiology in the Blavatnik Institute at HMS, and Ksenia Kastanenka, PhD, an HMS assistant professor of neurology at Massachusetts General Hospital. Their collaborative project focuses on Kv3 channels—proteins that enable nerve cells to generate nerve impulses. Bean and Kastanenka study Kv3 channels in GABAergic interneurons, vital for coordinating brain rhythms involved in memory, cognition, and sleep. Those rhythms are disrupted in patients with AD. Bean and Kastanenka will screen and refine compounds that act on Kv3 channels, then test the most promising candidates in mouse models to determine if they can restore normal brain rhythms.
“If successful, our work will result in the development of novel compounds that improve the function of interneuron-regulated circuits that are important for memory and cognition and are disrupted in mouse models of early AD,” Bean says. “Our hope is to eventually develop drugs that can improve memory in human AD.”
An earlier seed grant recipient, Sandeep Robert “Bob” Datta, MD ’04, PhD ’04, a professor of neurobiology at HMS, has investigated how the Ms4a gene family—strongly associated with late-onset AD in humans—may link the body’s immune system with microglia, the brain’s resident immune cells. His findings point to a previously unknown pathway involving peripheral T cells and microglia that may promote AD-related tau pathology. Datta is now finalizing this work for publication.
“It is so exciting to be able to explore the unexpected ways in which Alzheimer’s disease might induce neural damage through the coordination of multiple mechanisms, both inside and outside the brain itself,” Datta says. “Identifying these nodes of coordination might give us new therapeutic targets to attack AD on multiple fronts.”
Together, these projects illustrate the innovative, high-risk research that the Ludwig Neurodegenerative Disease Seed Grants Program is designed to advance.
“There is still much we don’t understand about the mechanisms that trigger Alzheimer’s disease,” says Carol Ludwig, MD, president of the Carol and Gene Ludwig Family Foundation. “We feel it is important to help support innovative efforts to decipher these initiating triggers, thereby advancing basic neurobiology and impacting future treatment development.”