Experimental Drug Reverses Hair Loss and Skin Damage in Mice

Older Man with Hair Loss

A recent mouse study from Johns Hopkins, published in Scientific Reports (July 30), shows that an experimental drug can successfully reverse hair loss, hair whitening and skin inflammation linked by previous studies to human diets heavy in fat and cholesterol.

In a series of experiments with mice, Johns Hopkins investigators used an experimental compound—D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP)—that halts the production of glycosphingolipids (GSLs), which are major components of skin and other cell membranes. Earlier research revealed that GSLs are prevalent in the cells that make up the uppermost layer of the skin, as well as in keratinocytes that help regulate pigmentation of the eyes, skin and hair. Mice fed a diet high in fat and cholesterol are more likely to have hair discoloration (from black to gray to white), extensive hair loss and inflammation of skin exhibited by multiple wounds. Feeding these animals D-PDMP, however, appears to reverse such symptoms.

The investigators caution that such results in mice do not mean that the same effects would occur in people, and there is no evidence at this time that the compounds they used would be safe in people. But the findings do shed light on possible pathways for addressing hair loss and skin wounds in humans with oral or topical medications.

“Further research is needed, but our findings show promise for someday using the drug we developed for skin diseases such as psoriasis, and wounds resulting from diabetes or plastic surgery,” says Subroto Chatterjee, PhD, MS, MSc, professor of pediatrics and medicine at the Johns Hopkins University School of Medicine.

To determine how disrupting GSLs might affect skin appearance and color, and whether treatment with D-PDMP would reverse any negative effects, Chatterjee and his colleagues first genetically modified a group of mice to have atherosclerosis, a disease in which arteries are clogged by fat deposits. The researchers then fed one group of these mice a Western diet high in fat and cholesterol, and a second group standard chow. All mice were fed their assigned diets from 12 weeks of age to 20 weeks.

Compared to those fed standard chow, the mice that ate a Western diet lost hair, formed skin lesions and suffered from hair whitening. These results became more severe when the mice continued eating a Western diet for 36 weeks, with 75 percent of the mice having hair loss and multiple skin lesions.

From 20 to 36 weeks of age, mice in both groups were given varying amounts of D-PDMP, either in a capsule or as a liquid, while they ate the same diet. Mice that received 1 milligram and 10 milligrams of D-PDMP in a capsule per kilogram of body weight from 20 to 36 weeks while eating a Western diet started regaining hair and hair color, and their skin inflammation lessened. Treatment with 1 milligram of D-PDMP in a capsule per kilogram of body weight was as effective as 10 milligrams per kilogram as a liquid, suggesting that an encapsulated form of D-PDMP is a better method of drug delivery.

The research team then looked at the skin of the mice under a microscope and found that mice eating the Western diet experienced an infiltration of neutrophils, a type of white blood cell implicated in inflammation, in various skin areas. Treatment with D-PDMP in a capsule significantly reduced the number of neutrophils, implying reduced skin inflammation and wounding.

Next, the researchers used mass spectrometry analysis to determine ceramide, glucosylceramide and lactosylceramide levels in the mice. Compared to mice fed normal chow, those fed a Western diet had decreased total ceramide levels, decreased glucosylceramide and nearly three times more lactosylceramide, a derivative of ceramide that activates inflammation. Treatment with 1 milligram of D-PDMP in a capsule per kilogram of body weight or 10 milligrams of D-PDMP as a liquid per kilogram of body weight, however, noticeably increased ceramide levels to normal.

“Our findings show that a Western diet causes hair loss, hair whitening and skin inflammation in mice, and we believe a similar process occurs in men who lose hair and experience hair whitening when they eat a diet high in fat and cholesterol,” says Chatterjee.

The study was funded by the National Institutes of Health.

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