Multiple Sclerosis - Vitamin D Hormone Blocks Multiple Sclerosis-Like Symptoms in Mice
Vitamin D Hormone Blocks Multiple Sclerosis-Like Symptoms in Mice
Encouraging Results may Lead to Human Trials
Doctors currently prescribe vitamin D compounds for the bone loss people experience because of several human diseases. It's also used to treat the skin disease psoriasis. Recent studies have suggested that the sunshine vitamin may have an unappreciated role in regulating the immune system.
Now three University of Wisconsin-Madison scientists have found that the active form of vitamin D -- also known as the vitamin D hormone, or 1,25-dihydroxyvitamin D3-- can effectively treat mice with a disease similar to multiple sclerosis.
Multiple sclerosis is the most common neurological disorder in the United States, affecting approximately 350,000 Americans. In MS, the body's immune system attacks parts of the spinal cord and brain. Depending on the severity and location of the attacks, people may develop numbness and paralysis of their arms and legs, fatigue, blindness, or other symptoms.
"Our results provide strong evidence that vitamin D is an important modulator of the immune system. We believe that vitamin D status may be an important factor in determining the incidence of multiple sclerosis," says Hector DeLuca, one of the UW-Madison scientists involved in the study.
"The bottom line is to find out whether this will allow us to help people," DeLuca says. "We can't be certain the vitamin D hormone will help those with MS until we do human trials." Other researchers have found compounds that block MS-like symptoms in the mouse model, but failed in human trials.
Margherita Cantorna, the immunologist who completed the experiments, and co-authors DeLuca and Colleen Hayes, both professors in the biochemistry department at UW-Madison's College of Agricultural and Life Sciences, published their findings in the July issue of the proceedings of the National Academy of Sciences.
DeLuca studies vitamin A and D. In the late 1960s he first identified the vitamin D hormone, which controls calcium metabolism in the body. Hayes studies the active form of vitamin A and its role as an inhibitor of inflammatory immune responses. DeLuca, Hayes and Cantorna conceived the experiments that led to the discovery.
The UW-Madison researchers studied mice with EAE -- experimental autoimmune encephalomyelitis -- a mouse model of MS. Most immunologists consider it the best animal model of MS, according to Hayes.
The scientists first showed that an injection of the active form of vitamin D given a day before they induced EAE in mice protected the mice from EAE.
In a second experiment the researchers induced EAE in 24 mice. When the mice began to show the initial symptom, a limp tail, the scientists gave 12 mice injections of the vitamin D hormone and added smaller amounts of it to their diet.
The vitamin D hormone blocked the progression of the disease in mice receiving it for the rest of the 40-day experiment. The mice not given vitamin D developed severe symptoms, including paralysis of the hind and fore limbs.
After 18 days, the researchers stopped giving the vitamin D hormone to half the 12 mice that had been receiving it. Within 10 days those six mice developed the same degree of MS-like symptoms as the mice that never received supplemental vitamin D hormone.
The researchers have begun tests to see if 1,25-dihydroxyvitamin D3 and its analogs will improve the health of EAE mice with nerve damage. Supplements of the vitamin D hormone elevate blood calcium levels in both mice and people, according to DeLuca. Therefore, the researchers anticipate testing analogs of the vitamin D hormone.
These analogs might block MS without affecting blood calcium level, Deluca says. He has identified and synthesized many such analogs and, through the Wisconsin Alumni Research Foundation, has patented several for treating MS. The Wisconsin researchers are hoping to find a pharmaceutical company that will work with them on human trials.