Research News

Cleveland Clinic neuroscientist Tara DeSilva, PhD, is tackling an unseen problem: brain lesions developing without symptoms during relapsing-remitting multiple sclerosis. 

Patients with relapsing-remitting MS experience symptom flares from heightened immune activity, but damage in the central nervous system continues even as symptoms lessen. That’s why neuroprotective drugs to prevent ongoing damage are so important. 

“Most treatments today focus on preventing immune cells from attacking the central nervous system and causing damage,” says Dr. DeSilva. “Our research has shown that after the initial damage, these lesions continue to ‘burn’ and cause additional neurodegeneration. To prevent further damage, we need to block the substance that signals this ongoing destruction.” 

Dr. DeSilva’s lab has begun to chart neurodegeneration in relapsing-remitting MS using the visual pathway, in collaboration with Cleveland Clinic’s Mellen Center. This pathway provides an easily tractable system to explore how damage to myelin, the insulation around neuronal axons responsible for proper nerve transmission, affects synapses. Synapses are specialized connections necessary for neurons to communicate. Through looking at this pathway, Dr. DeSilva’s lab also discovered a new target for neuroprotective drugs: excess glutamate associated with brain lesions. Although essential to brain activity, too much glutamate can be harmful. Dr. DeSilva's research shows glutamate levels rise in the brain even before lesions are detected. 

The research is now advancing in a project backed by a $1 million grant from the U.S. Department of Defense to investigate how blocking excess glutamate can prevent neurodegeneration, and ongoing work with Cleveland Clinic Innovations to transform this discovery into a new treatment for MS.

Drug discovery for relapsing remitting MS

Patients with relapsing-remitting MS make up about 80-85% of people diagnosed with MS. Dr. DeSilva’s research provides a clear starting point for a multi-pronged approach to developing treatments for this widespread disease, says Thomas Hattier, PhD, Senior Director for Innovations Development. 

“The discovery research nicely validated two distinct targets to address glutamate excitotoxicity in MS, giving Dr. DeSilva multiple options to pursue,” Dr. Hattier says. “Small molecules and nanobody-based approaches will be considered for therapeutic potential. Multiple target and drug modality options allows the process to move faster – if you hit a roadblock on one you have a parallel approach to pivot to.” 

Drug development spans Cleveland Clinic’s enterprise; Dr. DeSilva and the Innovations Team collaborate closely with the Center for Therapeutics Discovery, an in-house small-molecule research and development team that works with numerous researchers on translating discoveries to treatment. Development on these targets is still in the early stages. 

“What’s helpful when you collaborate with specialists in drug development and commercialization is that they don’t just focus on one path,” Dr. DeSilva says. “This collaboration allows researchers to make the most of their discoveries – not just through drug development but also making tests we’ve developed through our research available to others. These options allow us to accelerate our work to address critical problems facing our patients.”