Issue 106 Item 15 Vitamin D Analog Shows Promise in Treatment of Diabetes

A vitamin D3 analog arrests autoimmune diabetes in a mouse model, according to a report in the May issue of Diabetes. Dr. Luciano Adorini, Chief Scientific Officer at BioXell in Milan, Italy said, "Treatment of type 1 diabetes represents a formidable challenge that has, so far, defied all immunological approaches–actually all approaches, if we exclude insulin and diet.” "Our vitamin D3 analog has shown efficacy in a pre-clinical model, and there are a lot of indirect data suggesting a beneficial effect of Vitamin D3 in human type 1 diabetes."

Dr. Adorini and colleagues tested the effects of treating adult non-obese diabetic mice with Ro 26-2198, a vitamin D3 analog, daily for 4 or 8 weeks (at oral doses of 0.03 microgram/kg). Doses of 0.01 microgram/kg proved ineffective.

Daily treatment with Ro 26-2198, especially for the longer period, brought a significantly lower incidence of type 1 diabetes, the authors report, with only 16% of mice treated for 8 weeks developing the disease, compared with about 90% of control animals.

Ro 26-2198 treatment halted the recruitment of infiltrating cells into the pancreatic islets and left more functional islet beta-cells, the report indicates, but treatment did not induce hypercalcemia.

Treatment significantly inhibited lipopolysaccharide-induced production of interleukin-12 and gamma-interferon, the researchers note, and arrested the recruitment of gamma-interferon-producing T-helper cells into the pancreas, even as late as 14 weeks after Ro 26-2198 treatment was withdrawn.

Ro 26-2198 treatment also enhanced the percentages of CD4+CD25+ T cells in pancreatic lymph nodes, the report indicates. These regulatory T cells have been implicated in the mitigation of autoimmune disease in several experimental models.

"We have demonstrated that ongoing type 1 diabetes in the adult [non-obese diabetic] mouse can be arrested by a relatively short course of treatment with a [vitamin D3] analog," the authors conclude, "which is able to induce a selective inhibition of Th1 and an increased frequency of CD4+CD25+ regulatory T-cells in pancreatic lymph nodes."

"It remains to be seen if this may translate into a treatment," Dr. Adorini said, "and until then we must remain very cautious." Diabetes 2002;51:1367-1374.