Tailored Approaches May Lead to More Effective MS Treatments, UCLA Study Shows

Tailored molecular treatments for specific disabilities may be a breakthrough for multiple sclerosis (MS) patients, finds a new study by researchers at University of California-Los Angeles (UCLA).

The study, “Cell-specific and region-specific transcriptomics in the multiple sclerosis model: Focus on astrocytes,” appeared in the journal Proceedings of the National Academy of Sciences. Its senior author is Dr. Rhonda Voskuhl, director of UCLA’s Multiple Sclerosis Program.

Voskuhl’s team focused on astrocytes, a key type of brain cell that outnumber neurons by five to one and that are involved in MS.

Using a mouse model of the disease, researchers compared changes in gene expression — which typically leads to the production of proteins from DNA — by astrocytes in areas of the brain and spinal cord involved in walking, vision or behavior.

Results showed a decrease in the expression of genes involved in cholesterol synthesis in the spinal cord, which is critical for walking, and in the optic nerve, which is key for vision. Astrocytes are the main central nervous system cells that produce cholesterol in adulthood. The astrocyte-made cholesterol helps produce myelin — the protective coat surrounding neurons that is destroyed in MS — and plays a vital role in synapses, or communication among neurons.

Treating MS mice with a drug that increases cholesterol transport not only raised expression of cholesterol synthesis genes but also helped them walk better. Conversely, brain autopsy of MS patients demonstrated alteration of cholesterol synthesis pathways in the optic nerve similar to the findings in mice.

The discoveries led to the hypothesis that while inflammation causes loss of myelin and disrupts synapses, a drop in cholesterol synthesis gene expression in astrocytes may hinder nerve repair in MS.

Importantly, the study suggests that different molecular mechanisms underlie each disability. Therefore, neuroprotective treatments tailored for distinct disabilities may prove more effective than nonspecific treatments targeting a composite of different disabilities. This approach could be extended to other neurodegenerative disorders, researchers said.