Homotaurine Compound May Be New Class of Treatment for MS, Mouse Study Suggests

Homotaurine, a compound proven safe for humans in long-term clinical trials, has eased autoimmune responses, brain inflammation, and multiple sclerosis-like symptoms in a mouse model of the disease, a study has found.

The findings represent proof-of-principle evidence that homotaurine may represent a new potential class of treatment for multiple sclerosis (MS), the researchers suggested. 

The study “Homotaurine, a safe blood-brain barrier permeable GABAA-R-specific agonist, ameliorates disease in mouse models of multiple sclerosis” was published in the journal Scientific Reports.

Prior research in mouse models revealed that treatment with GABA (gamma-aminobutyric acid, glutamate), one of the most important messengers (or neurotransmitter) of the central nervous system (CNS), can restrain autoimmune responses and inhibit the development of diabetes type 1 and rheumatoid arthritis. Both are autoimmune diseases. 

Based on such promising data, researchers at the University of California hypothesized that GABA also could inhibit the autoreactive immune responses underlying MS, and work as a potential therapy for the disease.

However, GABA cannot cross the blood-brain barrier, a highly selective and semi-permeable barrier that protects the brain from toxins or microbes circulating in the blood. Thus, it is not well-suited to “inhibit the spreading of autoreactivity within the CNS,” the researchers wrote.

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So, the team looked at a different compound called homotaurine. This agent is able to stimulate the same receptors as GABA, but with the additional ability of traversing the blood-brain barrier.

Homotaurine was already tested in humans, specifically in a long-term study with Alzheimer’s patients. Although it was determined to be ineffective for that disease, it had an excellent long-term safety profile.

The therapy also has superior pharmacological properties compared with GABA itself, which makes it “an appealing candidate for treating inflammation in the CNS” as that underlying MS, the researchers noted.

The team sought to test if homotaurine would inhibit nervous system inflammation and prevent MS-like disease in a mouse model of MS — the experimental autoimmune encephalomyelitis (EAE) model.

In both chronic and relapsing-remitting models of the disease, researchers saw that oral administration of homotaurine after disease onset eased MS-like symptoms, including a reduction in inflammation of the spinal cord and brain.

Such positive effects were accompanied by a reduction in the frequency of self-reactive immune T-cells, specifically those releasing the inflammatory mediators IL-17A and IFNγ; and also by the expansion of T regulatory cells (Tregs) — immune cells that typically protect the body from attacks against its own cells and tissues.

Overall, according to the team, the study represents a proof-of-principle that brain-permeable GABA-related therapies may be “a new class of treatment” capable of limiting inflammation-mediated CNS disorders like MS.

In addition, it also provides insights into the roles of GABA signaling over the immune system, a function of the neurotransmitter that has not been explored extensively.