BIOCHEMISTRY

It’s been a long and winding road in the lab of Emeritus Professor Hector F. DeLuca when it comes to the effects of vitamin D and ultraviolet (UV) light on the disease multiple sclerosis (MS), a debilitating neurological disease with no known cure. Years of research in mice have led them to the understanding that it’s not vitamin D that offers protection from the disease but rather a slice of the ultraviolet spectrum helping in some mysterious way.

One place to begin the story is with a finding from a scientist named D. Goldberg. In the 1970s he observed that there was an inverse relationship between sunlight exposure and MS; less sunlight meant higher likelihood of the disease. He then took a leap and concluded it was a lack of vitamin D — which is actually a prohormone, a precursor to a hormone, created in the body thanks to sunlight exposure — that was playing a role in MS.

However, DeLuca had a hunch it wasn’t the vitamin D but something else.

“There was a lot of discussion about vitamin D being the important factor here and we decided that being vitamin D experts we should rigorously ask that question,” DeLuca explains. “We learned it wasn’t vitamin D but we’re still interested in the disease. So we went back to Goldberg’s original experiments with light and started to take apart the ultraviolet spectrum.”

To tease apart the effects of vitamin D versus UV light, the DeLuca Lab uses a mouse model that exhibits symptoms similar to those in human MS. They began experimenting with isolating parts of the spectrum to see which would protect against the disease. Through years of work, his team, led by assistant scientist Yanping Wang, learned the real relationship is between a band of ultraviolet light, one different from the band that produces vitamin D, and MS. Their results showed that longer UVA wavelengths did not offer protection, but shorter UVB, another type of UV radiation, wavelengths did.

Recently, assistant scientist Amy Irving has found that this narrow band of light does produce small amounts of vitamin D, adding to the need to definitively demonstrate that vitamin D production is not required for the protection offered by narrow band UVB. So, Amy worked with a mouse model that genetically lacks the ability to synthesize vitamin D in skin upon sunlight exposure.

“This narrow band works best to prevent the disease in the mouse model and even when we block vitamin D production in the skin to prevent the little bit that does occur, it still prevents the disease,” Irving says. “With the knockout mouse we can block the production of vitamin D in the skin so it doesn’t produce the precursor to
vitamin D. This was very important for our research.”

This line of research has yielded some serendipitous findings. For example, in one experiment where they were shining ultraviolet light on mice to simulate the sun, they applied sunblock to mice as a control. However, it turned out something in the sunblock itself was also able to prevent the disease and started yet another avenue of research in DeLuca’s lab. 

The relationship between vitamin D and neurological disease has been trickier to untangle. Some labs have shown that vitamin D deficiency offers protection from the disease, but that leads to other complications in the body. A large amount of vitamin D, on the other hand, also confers protection but only if it raises serum calcium above normal, which is very harmful to the body.

“I like the challenge of this research,” Irving says. “These are very difficult questions but they give us a lot of freedom to do experiments, and the challenge is making each one different from the last to try to figure this out in a different way.”

DeLuca says the ability of this narrow band of light to treat the disease is currently available through patents filed with the Wisconsin Alumni Research Foundation (WARF) and the team hopes it can be used in clinical trials on humans. Their ultimate goal is to dig deeper to understand more about how this narrow band confers protection from MS to try to devise treatments.

“I’m excited about just understanding how in the world this works,” DeLuca says. “It’s very intriguing and it has the byproduct of being beneficial to those with this terrible disease. What could be better?”

Top left thumbnail of Amy Irving by Robin Davies. 

Read about more research on vitamin D by DeLuca and others in the UW–Madison Department of Biochemistry:

Pike Lab Deciphers Final Pieces of Vitamin D Regulatory Pathway

Continuing a Legacy: Vitamin D Research in the 21st Century