ALS imaging research at U of M Medical School attracts $3M for a multicenter study to demonstrate clinical trial readiness of MRI biomarkers

Amyotrophic lateral sclerosis (ALS) is a condition that affects the brain and spinal cord, resulting in muscle weakness and wasting. Researchers from the University of Minnesota Medical School undertook a study to develop a reliable method for assessing changes in the disease's progression during clinical trials to evaluate the effectiveness of potential treatments. They recently received $3 million in research funding in two different grants, one from the U.S. Food and Drug Administration (FDA) and another from the State of Minnesota Office of Higher Education (OHE), to continue this research with a multicenter study.

Pramod Pisharady, PhD, an assistant professor at the Medical School’s Center for Magnetic Resonance Research (CMRR), led the study and served as the corresponding author of the research paper titled "Multimodal MRI improves diagnostic accuracy and sensitivity to longitudinal change in amyotrophic lateral sclerosis." Dr. Pisharady, the contact principal investigator of the new study, will lead the multicenter project with co-principal investigators and senior authors of the paper, Drs. Christophe Lenglet (CMRR) and David Walk (Neurology). The other two sites of the study are the University of Florida and Northwestern University

“Our recently published study demonstrates that brain imaging could be potentially used to assess changes in disease progression during clinical trials, indicating whether the tested treatments are having an effect.” Dr. Pisharady says. “In the new multicenter study, we aim to demonstrate the method's readiness for clinical trials and further develop the method to detect changes occurring in the brain and the cervical spinal cord in as little as three months, using advanced MRI techniques.”

The published study, which collected MRI data from 20 ALS patients and 20 healthy individuals, rescanning a portion of them at six-month and 12-month intervals, showed an improved ability to track ALS progression and enhanced accuracy in diagnosing ALS. The researchers achieved higher accuracy in diagnosing ALS by analyzing various metrics, including diffusion-based microstructural measures, cortical thickness, and spinal cord cross-sectional area. They could detect changes occurring over six months, compared to other methods that require a year. This suggests that the multimodal MRI approach can significantly help in diagnosing and tracking ALS progression, potentially serving as valuable markers in ALS clinical trials.

“The improved diagnostic accuracy this method provides is valuable for early ALS diagnosis. Furthermore, its ability to detect disease progression within six months has potential implications for developing effective treatments by evaluating whether the medications can cure or slow down the disease's progression,” explains Dr. Pisharady. “In addition to developing our method further with these new research findings, we hope to create one of the largest available longitudinal neuroimaging datasets in ALS with up to 90 ALS patients and 30 healthy individuals scanned at up to four time points over a year. This will enable and inform future ALS imaging studies by other groups.”

“The person I loved the most, my father, had a related neurological condition in his last few years. The diagnosis with late behavioral changes and the lack of treatment options made the situation difficult. I find this research in imaging a great opportunity to alleviate this difficulty for future patients and their loved ones,” Dr. Pisharady says.

The team of scientists and clinicians in the new multicenter study includes Christophe Lenglet, PhD, David Walk, MD, and Danni Li, PhD, from the Medical School; Eric Lock, PhD, from the U of M School of Public Health; Gaurav Guliani, MD, at HealthPartners Neuroscience Center;  Samuel Maiser, MD, at the Hennepin Healthcare; James Wymer, MD, and David Vaillancourt, PhD, at the University of Florida; and Senda Ajroud-Driss, MD, and Todd Parrish, PhD, at Northwestern University.

The published study has been made possible partly by a grant from the Chan Zuckerberg Initiative. The study was supported by funding from the National Institute of Health, the Bob Allison Ataxia Research Center, and the University of Minnesota Foundation.