Study of Genetic Variant Could Lead to Better Autoimmune Disorder Therapies

Study of Genetic Variant Could Lead to Better Autoimmune Disorder Therapies

A new study led by a research team at Oxford University suggests that pharmaceutically copying a genetic variant of a key protein could be a potential therapeutic strategy for autoimmune diseases.

Decreasing the potential risk of conventional treatment-related problems in the fight against autoimmunity could help people with a broad range of diseases, such as rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease (IBD), and systemic lupus erythematosus.

Current treatments for most systemic autoimmune disorders involve suppressing patients’ immune systems, which increases their susceptibility to infections and even cancer.

Utilizing scientific leaps in genetic research, researchers studied natural variants of the TYK2 gene, which is involved in the development of autoimmune diseases.

The team found that a genetic variant in TYK2 protects against the development of several different autoimmune diseases. This protection was mediated by a change in the TYK2 protein that reduced its function and decreased the activity of the immune cells, which could otherwise promote disease development.

The study, titled “Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity,” was published in the journal Science Translational Medicine.

In a nutshell, the study’s results indicated that new therapeutic approaches can be built by mimicking compounds of the TYK2 variant that guards against autoimmunity. Creating these pharmaceutical copies favors effectiveness, tolerability, and safety.

“Developing new drugs is a costly and time-consuming process. 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,” lead investigator Lars Fugger, professor of the Nuffield Department of Clinical Neurosciences at Oxford University, said in a press release. “This is because the majority of drugs fail to demonstrate sufficient efficacy to treat disease or they are associated with severe unwanted side effects.”

“While our research indicates that TYK2 could be a good drug target for treating autoimmune diseases, drugs that block the activity of immune cells have been known to leave patients vulnerable to infections and to increase the risk of cancer,” Fugger said.

“However, by interrogating data available through the UK Biobank, the most comprehensive health study in the UK, we found that people carrying the protective TYK2 genetic variant were no more likely to have serious infections or to develop cancer than people without the variant,” he added, underlining the key difference between their approach and already available pharmaceutical treatment options targeting other molecules.

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