Scientists unravel genetic clues to multiple sclerosis

Scientists have found 29 new genetic variants linked to multiple sclerosis (MS) and say the findings should help drugmakers focus treatment research on precise areas of the immune system.In a study published in the journal Nature on Wednesday, researchers said the newly-found links point to the idea that T-cells — a type of white blood cell responsible for mounting an immune response — and chemicals called interleukins play a key role in the development of the debilitating disease.

Drugs in development that target the immune system include rituximab, sold under the brand name Rituxan by Roche and Biogen to fight leukemia, Tysabri from Biogen and Elan, Lemtrada, sold as Campath by Sanofi’s unit Genzyme for cancer, and Abbott and Biogen’s Zenapax or daclizumab.

“We have implicated genes that are highly relevant to the actions of those drugs,” said Alastair Compston of Cambridge University, who co-led the study. “It is now clear that multiple sclerosis is primarily an immunological disease. This is the way to nail this disease and get on top of it.”

Mid-stage trial data for daclizumab released on Tuesday showed the drug on a par with other new medicines for MS, but some of he side-effects were worrisome.

Multiple sclerosis is one of the most common neurological conditions among young adults, affecting around 2.5 million people worldwide.

It occurs when the protective coating, known as the myelin sheath, around nerve fibres in the brain and spinal cord begins to break down, slowing the brain’s communication with the rest of the body.

The affected pathways — responsible for everyday activities such as seeing, walking, feeling, thinking and controlling the bowel and bladder — lose the ability to function properly and are eventually destroyed.

In a second study in the Public Library of Science journal PLoS Genetics on Wednesday, researchers found that many of the genes linked to MS are also linked to other autoimmune diseases such as Crohn’s disease and Type 1 diabetes. This also points to potential new uses for existing drugs in development, they said.

“We have known for some time that many devastating diseases of the immune system must have common genetic causes,” said Chris Cotsapas of Yale University in the United States, who led the PLoS study. “Now we have the outline of a map that tells us where we can look for common treatments.”

Most people who develop MS experience their first symptoms in their 20s and 30s, but Compston and colleagues told a briefing in London the trigger for the disease could happen in early childhood when genetic risk factors coincide with some as yet unknown environmental factor.

For their study, Compston and Peter Donnelly of Oxford University worked with some 250 other researchers and studied the DNA from 9,772 people with multiple sclerosis and compared it with a control group of more than 17,300 healthy people.

Their analysis confirmed 23 previously known genetic links and identified another 29 new genetic variants.

Experts think both genetic and environmental factors are equally important in determining who is likely to develop MS, and taken together, the known genetic variants probably explain about 20 percent of the genetic links, they said.

Previous research has suggested a link between Vitamin D deficiency and an increased risk of MS. Compston’s team said that along with the many genes which play a role in the immune system, they had also found two involved in the metabolism of Vitamin D — which mostly comes from sunlight — lending weight to a possible link between genes and the environment.

 

LONDON (Reuters) – By Kate Kelland(Editing by Hans-Juergen Peters)