The experimental therapy laquinimod was seen to prevent the start of harmful immune responses and to disrupt the progression of multiple sclerosis (MS) in a mouse model of the disease. This finding may be especially promising, as the treatment is being developed for people with both relapsing MS and its rarer progressive form, for which no treatment currently exists.
”We found that laquinimod treatment not only prevented spontaneous MS but also was successful when treatment was initiated after mice developed paralysis,” the researchers wrote in their study, “Treatment of spontaneous EAE by laquinimod reduces Tfh, B cell aggregates, and disease progression,” published in the journal Neurology.
Laquinimod is a novel oral compound with immunomodulatory properties that is being developed by Active Biotech and Teva to treat both forms of MS and Huntington’s disease. The drug has shown promising results in two phase 3 clinical trials, and is currently being tested in another Phase 3 trial in relapsing MS patients (CONCERTO, NCT01707992), and in a Phase 2 trial in primary progressive MS patients (ARPEGGIO, NCT02284568). But the mechanisms behind its effects are not well understood.
Researchers studied a mice model of MS, and treated the animals daily with either laquinimod in drinking water or with pure water. After 10 days of treatment, the number of immune T-cells, B-cells, and antibodies in the mice were examined.
Results showed that only 29 percent of the laquinimod-treated mice developed MS, compared to 58 percent in the untreated group. In addition, when the team treated mice that had already developed paralysis, laquinimod was seen to disrupt disease progression. These results indicate that laquinimod may work to help prevent MS development and be beneficial in progressive MS — a more advanced stage of the disease.
The team also identified some possible mechanisms of action of laquinimod in MS. In treated mice, researchers observed:
- A 96 percent reduction in harmful clusters of B-cells — clusters only seen in patients with progressive MS.
- An almost 50 percent reduction in dendritic cells that help to create special T-cells, which in turn help B-cells to survive, and an almost 50 percent reduction in these particular T-cells.
- A 60 percent reduction in harmful antibodies.
In a healthy immune response, T-cells and B-cells help to prevent infections. In MS, however, these same cells create antibodies that attack and destroy the myelin sheet, which is the protective, fatty layer that surrounds nerves in the brain and spinal cord.
Myelin is needed for the nerve cells to communicate properly, and damage to the myelin sheets leads to impaired or lost signals between nerve cells. This is the mechanism underlying disease progression and disability in MS patients.
Laquinimod was seen to not only have preventive properties against MS, but to also disrupt the progression of the disease, providing hope that it might be a potential treatment for progressive MS. In bringing fresh insight into the action mechanisms of laquinimod, the study also may lead researchers to a better understanding of the causes of this disease.
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