Scientists unravel genetic clues to multiple sclerosis

Multiple sclerosis patient Sue Sutton (L) embraces Dare, a two-legged Sheltie dog used in therapy for disabled people in Denver, Colorado July 15, 2009.

Credit: Reuters/Rick Wilking

By Kate Kelland

LONDON | Wed Aug 10, 2011 3:55pm EDT

LONDON (Reuters) - 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.

(Editing by Hans-Juergen Peters)

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China helps unravel new E.coli for embattled Europe

By Tan Ee Lyn

HONG KONG, Jun | Fri Jun 3, 2011 9:23am EDT

HONG KONG, Jun (Reuters) - For three long weeks Europe was gripped with fear battling a mysterious E. coli epidemic, and it wasn't until late this week that China's genomics institute nearly 7,000 km away finally put its finger on the culprit.

Chinese scientists at the Beijing Genomics Institute, the world's largest DNA sequencing center, announced late on Thursday that the E. coli spreading through Europe was "a new strain of bacteria that is highly infectious and toxic."

The researchers, who obtained DNA samples of the bacteria from collaborating scientists in Germany, managed to fully sequence its genome in three days -- becoming the first in the world to do so and lodge its full sequence on the Internet.

They also identified genes in the bacteria that gave it resistance to at least three major classes of antibiotics, which helped explain why doctors in Europe have had such a hard time fighting the bug, that has killed 17 people and made more than 1,500 others ill.

Work continues at BGI's main research arm in Shenzhen city, which lies just north of Hong Kong, to fully characterize the bacteria.

"We have done further analysis and see even more antibiotic-resistant and toxic genes. Our work is still ongoing," said Qin Junjie, a member of the team that sequenced the bacterium and is now analyzing it.

The three classes of antibiotics the Chinese scientists identified as ineffective in fighting the bacterium are first-line drugs commonly used to fight gastro-intestinal infections and as surgical prophylaxis.

"It means doctors have a more limited arsenal among first line drugs (to fight this bacteria)," said William Chui, vice president of the Society of Hospital Pharmacists in Hong Kong. Chui was not involved in the sequencing study.

In Europe, authorities are still hunting for the source of the epidemic, which is believed to have contaminated raw vegetables. Without nailing the source, experts fear they may not be able to contain the crisis.

BIGGEST DNA ANALYSER IN THE WORLD

This new strain bears the hallmarks of other E. coli strains that are known to cause symptoms such as bloody diarrhea, or hemorrhagic colitis, and hemolytic-uremic syndrome, which damages the kidneys.

"This bacteria is a strange creature. Many of its genes seem to have been transferred from (distant) E.coli strains, which provide this strain with the ability to cause hemolytic uremic syndrome and/or bloody diarrhea," said Qin, vice president of BGI's Microbiology Transomics Center.

To most people, China's involvement in unraveling this bacterium terrorizing Europe comes as a surprise, particularly as it is still remembered for trying to cover up SARS in 2003.

But to the industry observer, China has come a long way between then and now.

BGI's research arm in Shenzhen city is strongly backed by the local government, one of China's wealthiest.

BGI in Shenzhen also provides DNA sequencing and other research services for industry and private individuals and income earned is pumped back into research and development.

It has over 180 sequencing machines, giving it the biggest DNA sequencing capacity in the world, and a total workforce of over 4,000, said Yang Bicheng, BGI's marketing director.

"For sequencing alone, we have about 300 researchers," she told Reuters by telephone on Friday.

"We are now trying to understand the toxic genes (of the new E. coli). We are still doing analysis to further identify the functions of these genes," said Yang, a scientist by training.

"We are developing a diagnostic kit. We are testing it now and hope to get approval for it soon. It will be used to detect the bacteria in food and also in people."

Asides from sequencing DNA, BGI has pumped in plenty of resources in recent years into animal cloning and improving its rice breeds and other agricultural products to increase yields, which China hopes would eventually help in feeding its growing population.

BGI scientists, some of whom have been trained in leading universities in the United States and Europe, have even modified its in-house cloning techniques, enabling each researcher to clone up to 200 pig embryos in a single day.

It recently set up a unit to commercialize cloning and meat from the offspring of cloned pigs is expected to be available on the Chinese market in a few years.

(Editing by Alex Richardson)

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