Psoriasis drug shows promise in diabetes trial

A drug previously used to treat psoriasis has shown positive results in a phase II trial assessing its effectiveness at treating type 1 diabetes, according to a study published in The Lancet Diabetes and Endocrinology.

The drug, alefacept, is an immune-suppressing drug that has been used to treat psoriasis, a common skin condition, for around a decade.

According to the team of US researchers, there have been trials in the 1980s and 1990s that explored the use of immune-suppressing drugs to treat type 1 diabetes. But they say the long-term use of immunosuppressant therapy at that time outweighed the benefits.

However, more recent immune-suppressing drugs have been developed to target specific cells that trigger autoimmune disorders, while avoiding the immune cells needed for normal immune functioning.

Alefacept, marketed as amevive but withdrawn by its manufacturer in 2011, works by attacking specific T cells (a type of white blood cell). These include Tem (effector memory) cells, and on a lower scale, Tcm (central memory) cells, which the researchers say are "involved in the body's mistaken attack against itself."

Because type 1 diabetes involves the process of Tem Cells and Tcm cells attacking insulin-producing cells in the pancreas, the researchers wanted to see what effect alefacept had on patients who had been newly diagnosed with the condition.

The researchers, led by Professor Mark Rigby of Indiana University and the Riley Hospital for Children in Indianapolis, recruited 49 patients from 14 different US institutions.

Alefacept injections were given to 33 of the participants weekly for a period of 12 weeks, followed by a break of 12 weeks, before a further weekly dose of the drug for another 12-week period. The other 16 participants were given a placebo and followed the same schedule.
Alefacept found to preserve insulin secretion
Injection
Alefacept, a drug formerly used to treat psoriasis, has performed well in a Phase II trial assessing its effectiveness against type 1 diabetes.

In analyzing how well the pancreas was able to secrete insulin in response to food 2 hours after eating, the researchers found no difference between the two groups.

However, when looking at insulin secretion 4 hours after food, it was found that the group prescribed alefacept showed preserved insulin secretion, compared with the placebo group who showed decreased levels of insulin.

On reviewing the participants 12 months after receiving treatment, the group who used alefacept showed no significant increase in insulin use over the course of the trial period, compared with the placebo group.

The participants who used alefacept also reported fewer episodes of hypoglycemia - low blood glucose levels. These episodes are a common ocurrance in patients who need insulin shots.

The researchers say these results suggest that alefacept "preserved the body's ability to produce its own insulin."
Disease-causing cells depleted

Furthermore, the drug was found to diminish potentially disease-causing Tem and Tcm cells, while avoiding immune-regulating T cells.

The researchers say the "selective" action this drug has on the immune system may show improvements on earlier drugs known to induce "general immune suppression."

Prof. Rigby explains:

    "Alefacept is the first targeted biological drug assessed in patients with new-onset type 1 diabetes that significantly depleted the T cells which attack the pancreas in type 1 diabetes, while preserving other immune cells which are important for pancreatic function.

    Although the primary endpoint was not met, several key secondary endpoints were significantly different between treatment groups, suggesting that alefacept might preserve pancreas cell function during the first 12 months after diagnosis."

He continues that although targeting memory T cells could be a useful strategy in treating type 1 diabetes, a longer follow-up period is necessary to confirm the efficacy seen at 12 months in the trial.
'Closer to stopping or reversing type 1 diabetes'

In a comment article linked to the study, Dr. Kevan Herold of Yale University says that these results, along with recent trials of a "CD3 monoclonal antibody," are leading to mechanism-based strategies to restore the balance between cells needed for protection against pathogens and those that "maintain tolerance to self rather than broadly eliminating immune cells."

"It is important to underscore these small successes since, as in other fields such as oncology and infectious diseases, the small achievements acquire greater significance when they are combined," he adds.

"In this regard, the withdrawal of pharmaceutical companies from this and other trials, even before the final outcomes of trials were realized, was disappointing - particularly as we move closer to finally reaching the ultimate goal: to prevent, stop, and even reverse type 1 diabetes."

It was recently reported on a study revealing how a biomarker that determines the risk of type 2 diabetes may be linked to certain lifestyle and demographic factors.

Credit: Honor Whiteman(MNT)