Americas Committee for Treatment and Research in Multiple Sclerosis
West Palm Beach, Florida


NIH Scientist Predicts Precision Medicine Using Spinal Fluid Measures Will 'Revolutionize Neurology' in the Treatment of Multiple Sclerosis

Bibi Bielekova, MD, Chief of the Neuroimmunological Diseases Section at the National Institutes of Health, predicts that precision medicine will come with more advanced knowledge of spinal fluid biomarkers that can predict future disease progression in MS.WEST PALM BEACH, FL — The chief of the neuroimmunology section at the National Institutes of Health (NIH) doesn't think NEDA (no evidence of disease activity) is a very good measure of treatment efficacy in multiple sclerosis (MS). Bibi Bielekova, MD, said she would love to see "NEDA" (no new lesions, no evidence of disease progression) in her patients with MS, but overall this is a poor measure of therapeutic response because it fails to distinguish between what she called "lesional versus non-lesional activity" in patients with MS.

Speaking at the second day of the Americas Committee for Research and Treatment in Multiple Sclerosis (ACTRIMS) Forum on Friday, February 28, Dr. Bielekova discussed how machine learning and data-mining approaches can be used toward more accurate detection of therapeutic response in MS. Eventually this information can be fine-tuned so that therapies can be targeted using precision medicine—that is, given only to patients shown via biomarkers to respond to that particular immunomodulatory approach.

The current definitions of therapeutic response in MS are deficient in several ways, Dr. Bielekova proposed. "Using these definitions, a non-responder would be anybody who develops an episodic outcome such as new or contrast-enhancing lesions, and a responder would be anyone who doesn't," she said. But this approach gives essentially the same weight to episodic outcomes and continuous outcomes, such as significant clinical or subclinical disease progression. "To understand the biology that underlies and eventually predict therapeutic efficacy, we need to estimate disease severity and activity before the initiation of treatment," she said.

"Because our drugs are so good at inhibiting lesional activity, continued disease progression must be due to non-lesional activity," Dr. Bielekova proposed. "However, our current drugs have negligible therapeutic effect on this non-lesional activity in MS."

She also argued that "correlations are not causality." An outcome in MS or any other disease may be causal or epiphenomenal, meaning that multiple factors have influenced that outcome. More objective measures, such as cerebrospinal fluid (CSF) markers, are the next wave of precision medicine. Her research group is using a CSF biomarker-based model and machine learning techniques to predict future rates of MS disability progression. The team measured over 1,000 CSF proteins in 431 patients with neuroimmunologic diseases and healthy volunteers. Several astrocyte and microglial clusters were reproducibly elevated in MS. These CSF markers had a significant and reproducible correlation with MS severity, suggesting a pathogenic role, the research showed.

Her department is currently engaged in a clinical trial at NIH called "Targeting Residual Activity By Precision, Biomarker-Guided Combination Therapies of Multiple Sclerosis (TRAP-MS)." This trial will evaluate how different MS drugs, given alone or in combination, affect CSF biomarkers, to see if changes in biomarker levels can predict these individuals' response to MS drugs.

"CSF biomarkers have the potential to revolutionize neurology," Dr. Bielekova predicted, "by facilitating discoveries and validation of therapeutic targets [and] providing patient-specific information necessary for precision medicine."


By Katherine Wandersee, for the Consortium of Multiple Sclerosis Centers (CMSC)


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