New Hope on the Horizon for Fighting Leptomeningeal Disease
Leptomeningeal disease is a type of cancer that causes severe neurological symptoms that negatively impact quality of life and is resistant to all standard-of-care therapies. It is an aggressive and often untreatable cancer that spreads to the membranes surrounding the brain and the spinal cord, hindering neurological functions.
But researchers in the Inna Smalley Lab at Moffitt Cancer Center say they are on the verge of something exciting. A new study has uncovered a potential breakthrough involving the role of branched-chain keto acids, which are naturally occurring byproducts of metabolism, in helping cancer evade the immune system.
“We found that branched-chain keto acid buildup in the cerebrospinal fluid of leptomeningeal patients and accumulation of those metabolites stop immune cells from doing their job,” said Mariam Lofty Khalad, PhD. “That gives the disease a chance to grow unchecked.”
Khaled will present the research at the American Association for Cancer Research 2025 conference in Chicago.
The discovery associating the acids with leptomeningeal disease also means there could be a promising treatment on the horizon.
According to Khaled, phenylbutyrate, a safe, U.S. Food and Drug Administration-approved medicine used to treat a rare metabolic disorder called maple syrup urine disease, improved survival of neurological health in lab tests.
“This could change everything,” Khaled said. “We’re not just seeing better outcomes in our models, we’re seeing a new strategy to treat patients who haven’t had many options.”
Because phenylbutyrate is already approved for use in humans, Moffitt’s research team believes clinical trials could begin soon. The goal is to combine phenylbutyrate with existing cancer treatments like CAR T, or chimeric antigen receptor therapy, especially in patients with lymphoma who develop leptomeningeal disease.
Leptomeningeal disease most often occurs in patients with breast cancer, lymphoma, lung cancer and melanoma.
“This treatment could be a game changer for patients,” Khaled said. “And we hope to bring it to the clinic very soon.”
