Along with the central nervous system, the immune system may play a fundamental role in Amyotrophic Lateral Sclerosis (ALS), suggesting that bone marrow transplants may be an effective novel treatment for the neurodegenerative disease, according to findings from a research team that included Albert LaSpada, MD, Ph.D., distinguished professor of pathology, neurology and biological chemistry at the University of California, Irvine School of Medicine.
The study, "Clonally expanded CD8 T cells characterize amyotrophic lateral sclerosis-4," recently published in Nature, was a joint collaboration between LaSpada and Mount Sinai microbiology faculty members Laura Campisi, PhD, and Ivan Marazzi, PhD. The team found both immune and nervous system dysfunctions in animal models and patients with ALS4, a juvenile and slowly progressive form of the condition caused by mutations in the senataxin protein-coding gene.
This is the first study to implicate altered cell-mediated immune system function in ALS and raises the prospect of abnormal cell mediated immunity as a contributing factor in not only ALS4, but also in other forms of the disease, including sporadic ALS, which accounts for 90 percent of all cases."
Albert LaSpada, MD, PhD, Distinguished Professor of Pathology, Neurology and Biological Chemistry, Irvine School of Medicine, University of California
ALS is characterized by the progressive death of motor neurons, which severely impairs the patients' ability to move their arms and legs, speak, swallow and eventually, breathe. There is no treatment or cure, and previous research has focused on neurons. More recent studies, however, have shown evidence of interaction between the central nervous and immune systems.
The team's most important discovery was that cell-mediated immunity, which does not involve antibodies, is altered in ALS4, based on the presence of expanded CD8 T-cells. These cells contribute to motor neuron degeneration in ALS4, validated by further research showing that replacement of bone marrow in ALS4 mice with normal control mice bone marrow was an effective treatment.
"The therapeutic benefit conferred by bone marrow transplantation in ALS4 mice can now be considered as a treatment for human patients. Furthermore, although ALS4 is a rare familial inherited form of ALS, it shares the same cardinal histopathological findings observed in sporadic ALS and most other familial forms. Hence, if future research implicates an aberrant CD8 T-cell response in sporadic ALS, then bone marrow transplantation could be a novel treatment approach for many ALS patients in the future," LaSpada said.
Considering the potential therapeutic opportunities suggested by this work, LaSpada recommends the next steps should be to re-evaluate cell-mediated immunity in sporadic ALS patients to determine if altered T-cell function is a feature of their disease process.
University of California – Irvine
Campisi, L., et al. (2022) Clonally expanded CD8 T cells characterize amyotrophic lateral sclerosis-4. Nature. doi.org/10.1038/s41586-022-04844-5
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Tags: Amyotrophic Lateral Sclerosis, Anatomy, Antibodies, Bone, Bone Marrow, Cell, Central Nervous System, Education, Epidemiology, Gene, Genetic, Immune System, immunity, Medicine, Microbiology, Motor Neurons, Nervous System, Neurodegeneration, Neurodegenerative Disease, Neurology, Neuron, Neurons, Pathology, Pharmacology, Physiology, Protein, Public Health, Research, Sclerosis, students, T-Cell
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