Retinoid-X Receptor Agonist as a Treatment for Multiple Sclerosis

A study reported in NewsWise evaluates retinoid-x receptor (RXR) agonists as a treatment for recurring and refractory multiple sclerosis (MS). This specific RXR agonist, bexarotene, was found to help remyelination, therefore improving the symptoms.

About Multiple Sclerosis

Multiple sclerosis (MS) is a neurological disorder that affects the sending of signals from the brain to the body. When one has this disorder, their immune systems attack myelin, which is the protective covering of nerve cells.  In severe cases, these nerves can be damaged permanently. There are two types of MS, relapsing/remitting or progressive. The former is characterized by long periods without symptoms followed by episodes of intense symptoms. Progressive MS does not include periods without symptoms, instead people constantly feel the effects of the disorder. It can result in the loss of daily function.

Symptoms of multiple sclerosis can vary from patient to patient; all parts of the body can be affected. Muscles in the extremities and the eyes are most commonly affected. The first symptoms often appear between the ages of 20 to 40, which could be weakness, numbness, loss of coordination and balance, or problems with speech, vision, and bladder control. While there is currently no cure for MS, specific symptoms can be treated.

There is also no known cause for MS. It is an autoimmune disease, which occurs when the immune system attacks parts of the body, in this case myelin. These attacks result in the slowing or blockage of neuro messages. It is suspected that there is a hereditary element, but a combination of genetics and environmental factors are most likely the cause. What is known is that this disorder can occur at any age, but is most common from the ages of 15 to 60, and women are twice as likely to have it.

About the Trial

Researchers took on this trial with the goal of evaluating the safety and efficacy of bexarotene. The trial itself was placebo-controlled, double-blind, and enrolled adult patients under the age of 50 who were stable for six months while being treated with dimethyl fumarate. The primary endpoint was mean lesional magnetisation transfer ratio, while the secondary endpoint was change in full-field visual evoked potential (VEP) latency in the eyes.

52 patients were enrolled and administered either 300mg/m2 of bexarotene or a placebo for six months. At first, results seemed to be negative. There were adverse effects, with five patients discontinuing their treatment because of them. The most common were central hypothyroidism, neutropenia, rash, and hypertriglyceridaemia. The primary endpoint was also not met.

However, further investigation into lesions on the brain found that the treatment did have an effect on magnetisation transfer ratio. Researchers also noted that the secondary endpoint was met. This led them to the conclusion that retinoid-x receptor agonists promote remyelination in those with multiple sclerosis. While further research is needed, this is a very good start.

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