May 23, 2024

ALS Immune Findings Yield Important Results

A new study by Dr. Benjamin Murdock uncovers important information that will shape therapeutic strategy, diagnosis, and prognosis in ALS.

Previous research by Robert A. Epstein and Joan M. Chernoff-Epstein Emerging Scholar Benjamin Murdock, Ph.D., has shown that multiple immune cell types likely contribute to ALS progression and survival.  He has also discovered that the immune system of ALS patients differs based on specific demographics (age and sex).  His new study sought to determine which immune cells and pathways affect ALS and whether this effect changes with different patient demographics.

To do that, Dr. Murdock and his team combined multiple immune markers into a single analysis, examining their association with disease progression and survival in groups of patients separated by age and sex.  They also wanted to determine if adding immune markers to predictive models of ALS improved accuracy.

What did they find?

Multiple immune markers were associated with ALS progression and survival, including neutrophils, lymphocytes, natural killer (NK) cells, specific NK cell subpopulations and surface proteins.  Also, these associations were, in fact, age- and sex-specific, and each group (younger women, younger men, older women, and older men) had a different immune “fingerprint,” suggesting that how the immune system works in ALS differs based on a patient’s age and sex.  Furthermore, when they created predictive models for a patient’s future disease course, they found that adding immune markers dramatically increased the predictive power of the models.

What does this mean for patients?

“Our findings suggest that previous immune-based clinical trials may have failed because different groups of patients require different treatment strategies, since they have different immune markers,” explained Dr. Murdock.  “Simply treating every ALS patient with the same immune drug may not be a viable strategy.”

He explained that future studies should account for a patient’s demographics and revisit former clinical trials to determine whether previously failed drugs may be effective in specific patient groups. In addition, the increase in short-term prediction accuracy suggests that immune markers can be used to indicate future disease diagnosis and prognosis.

Additional authors include Bangyao Zhao, BS, Kristen D. Pawlowski, Joshua P. Famie, BS, Caroline E. Piecuch, BS, Ian F. Webber-Davis, BS, Samuel J. Teener, BS, Eva L. Feldman, MD, PhD, Lili Zhao, PhD, and Stephen A. Goutman, MD, MS.

Paper cited: “Peripheral Immune Profiles Predict ALS Progression in an Age- and Sex-Dependent Manner” Neurology Neuroinflammation & Neuroimmunology. DOI: 10.1212/NXI.0000000000200241