Lingo

bromley · Family Elder Joined: Sep 11, 2004 Posts: 1819

HarryZ will like this story - it shows what nice folks Biogen are.

Biogen Idec testing regenerative medicine drug to reverse the path of Multiple Sclerosis 27 August 2008

Biogen Idec has made a lot of its money on Avonex and Tysabri, drugs that slow down the rate of flare-ups for people with multiple sclerosis. Now the Cambridge, MA-based biotech company is pursuing a loftier goal. It is working on the first experimental drug that may reverse the symptoms of the neurodegenerative disease.

The drug, being tested in animals and prepped for its first human trial, is designed to block a protein called Lingo-1 that interferes with body’s production of myelin, the fatty protective coating around nerve fibers. People with multiple sclerosis have an overactive immune system that eats away at the myelin layer, and they have no ability to regenerate myelin in the brain or spinal cord, says Sha Mi, a Biogen researcher. That means nerve impulses that control speech, vision, and movement get short-circuited, sort of like when an electrical wire is stripped of its insulation. Biogen thinks it now has engineered a drug that can stop Lingo-1 from doing its dirty work, allowing the body to regenerate myelin coating around nerves. That could restore normal functions, like walking.

“People around the company are very excited about this,” says Kenneth Rhodes, Biogen’s vice president of discovery neurobiology. “It’s potentially a transformational therapy.” Sha Mi, the Biogen scientist who discovered the molecular switch that paved the way for the program, put it this way, “As a scientist, I came all the way from China. If we can create a new medicine to affect patients, that is my dream.”

The drug hasn’t even entered clinical trials yet, and it’s already been an eight-year odyssey. Sha Mi (who goes by the name Misha) joined the company in 2000 from Wyeth’s Genetics Institute unit in Cambridge, MA. Not long after joining Biogen, she found the Lingo-1 protein in a database and learned it was expressed solely in the central nervous system and, then, only in neurons. Later experiments showed that when scientists delete the gene that makes Lingo-1 in mice, those altered mice would recover from a disease in which the immune system eats away at myelin, called autoimmune encephalomyelitis. The same recovery was seen in mice when they were given an antibody drug designed to block the Lingo-1 protein. There were no side effects or dangers seen from producing too much myelin, because the body will only produce the amount needed to cover nerves, Sha Mi says. The combination of experiments, conducted by Biogen scientists and collaborators in China, made the cover of Nature Medicine last October.

Other researchers are working on myelin repair, such as a group led by Bruce Trapp at the Cleveland Clinic, says Rhodes, the Biogen vice president. Madison, NJ-based Wyeth has attempted to develop conventional small molecule drugs against Lingo, but hasn’t been successful, he says.

Biogen is developing a genetically engineered antibody against Lingo because that approach should do a better job of binding with the Lingo protein target on the surface of cells, Rhodes says. The first version, however, wasn’t quite “optimal,” and a newer one is being engineered with better properties, he says. The latest version is made with fully human DNA, instead of partial mouse DNA, because researchers want to be confident that the drug won’t spark the immune system to reject it, especially if it needs to be given chronically. The company is planning to ask the FDA for permission to start its first human clinical trials, although he wouldn’t say when.

No details are available yet on how the trials will be crafted, but Rhodes made clear that the company’s vision is for Lingo to be used in combination with Avonex or Tysabri. The idea is that those drugs can reduce the immune system’s assault on neurons, quieting the storm. That would give an opportunity for the anti-Lingo-1 drug to step in and regenerate myelin around the nerves.

Since 400,000 people in the U.S. suffer from MS, and there’s nothing else quite like this program poised for clinical trials, it seems unlikely that Biogen will have much trouble recruiting patients in the first study. If they show they can regenerate myelin in even a few people, Biogen will be a few steps closer to fulfilling Sha Mi’s dream.

Source: Xconomy © 2007-2008 Xconomy (27/08/0 Cool

Lyon · Posted: Wed Aug 27, 2008 6:51 am Post subject:

CureOrBust · Posted: Wed Aug 27, 2008 7:47 am Post subject:

the heartening thing is anti-lingo1 treatment has nothing to do with their assumption based on "an overactive immune system". The other thing is, they had to make it digestible by the general public, so I would guess they "dumbed it down". Its also not a specific quote from the researchers, so could have been from "research" by the reporter. Bigens' quote actual explicitly talks of Avonex or Tysabri reducing the inflammation (NB: note, no specifics about the immune response) and giving this treatment a chance to work.

gwa · Family Elder Joined: Dec 02, 2005 Posts: 792