Genetic Variant May Protect Against IBD, Could Be Target for New Therapies

Genetic Variant May Protect Against IBD, Could Be Target for New Therapies

People who have a particular variant of a gene called TYK2 are naturally protected against autoimmune diseases such as inflammatory bowl disease (IBD), according to a study published in the scientific journal Science Translational Medicine.

This finding suggests that drugs that target the TYK2 gene or mimic the protective effect of the TYK2 genetic variant could be developed to treat IBD as well as other autoimmune diseases.

Although the majority of drugs that treat autoimmune diseases are not sufficiently effective and may be associated with severe side effects such as increased risk of infections and cancer, people who have the protective TYK2 genetic variant are no more likely to have serious infections or to develop cancer than people without the variant, according to Prof. Lars Fugger of the University of Oxford. Targeting the TYK2 gene could therefore mean new therapies with fewer side effects.

Fugger is the senior author of the study “Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity.

Using data obtained from the U.K. Biobank, researchers performed genetic meta-analysis across diseases. They then conducted molecular, cellular, structural, and functional studies, linking these to epidemiological data.

They found that the TYK2 genetic variant reduces the function of the protein that the gene encodes for, and that plays an important role in immunity. However, the activity of the TYK2 protein can also be linked to autoimmune diseases. A reduced TYK2 function means that the activity of autoimmune cells is also dampened and this offers protection against autoimmune diseases.

According to the authors, people with the genetic variant of the TYK2 gene possess an optimal degree of immunity: low enough to be protective against autoimmune disease and high enough to prevent immunodeficiency.

Although TYK2 could be a potential target for the treatment of several autoimmune diseases, including IBD, Fugger cautioned in a press release that the development of new drugs is costly and time-consuming.

“On average it costs over £1 billion [pounds] and takes over 10 years to bring a new drug to market, and more than 90 percent of drugs that enter into clinical trials are not ultimately approved,” he said.

The results of this study are promising, but they are a small step in the quest to develop efficient drugs for the treatment of IBD and other autoimmune diseases.