Reversing the damage done by multiple sclerosis would be a dream come true for patients of the debilitating disease, and there is some promising research working toward that goal.
The condition is thought to occur when the body literally attacks itself and current therapies only seek to slow or stop that situation. But Biogen Idec Inc. (BIIB) is developing a drug that may repair the damage to the nervous system from the disease, a prospect that could also aid victims of other neurological conditions.
"This is the first entry into our clinical pipeline, or really in anyone else's pipeline that we are aware of, for a truly restorative therapy for MS," said Ken Rhodes, vice president of discovery neurobiology at Biogen.
Though the Cambridge, Mass., biotech company is hopeful for the drug's development, it is yet to be tested in humans and, assuming success, it wouldn't be available to patients for many years.
Much remains unknown about multiple sclerosis, but it is thought to be an autoimmune disease that occurs when the body attacks myelin, the protective insulation surrounding the nerve fibers called axons in the central nervous system. The myelin damage can distort or block messages carried by the axons and result in a wide variety of symptoms such as vision problems, limb numbness and paralysis.
Though the cause is a mystery, MS is thought to develop from some degree of genetic predisposition working in combination with environmental triggers earlier in the life. It is more common in women and tends to develop between the ages of 20 and 50, according to the National Multiple Sclerosis Society.
Current treatments for the disease all involve trying to alter the immune system's ability to attack the nervous systems, notes John Richert, executive vice president of research and clinical programs for the MS Society.
A popular group of drugs are the beta-interferons, which reduce disease flare ups and are similar to proteins that play a role in the immune system. Those are Biogen's Avonex, Bayer AG's (BAY.XE) Betaseron, and Rebif, marketed by Pfizer Inc. (PFE) and Germany's Merck KGaA (MRK.XE).
Teva Pharmaceuticals Industries Inc. (TEVA) makes Copaxone, which seems to fight the nerve-attacking immune cells by acting as a myelin decoy. Biogen and partner Elan Plc (ELN) also sell Tysabri, which prevents those immune cells leaving the blood stream so that they can't get to the brain or spinal cord.
The focus of much of Biogen's current discovery research in MS is focused on restorative therapy, but its most advanced program is led by biologist Sha Mi, who joined the company in 2000 and studied why the axons in MS lesions weren't generating new myelin.
Research found that cells called oligodendrocytes were being prevented from undergoing the needed differentiation for them to build new myelin.
Furthermore, Mi found that the so-called LINGO molecule was inhibiting that differentiation and that using an antibody to block LINGO's function could allow myelin to regenerate.
"When we block LINGO function, we can see robust oligodendrocyte differentiation, and they interact with the axon for remylination," said Mi.
The antibody has been shown to be effective in mouse models that are accepted as being useful for mimicking the properties of MS.
The antibody helped the mice grow new myelin, and it also helped with the integrity of the nerve fibers, in comparison to untreated mice, thus aiding nerve function. More myelin growth occurred closer to the site of the antibody application, also suggesting its responsibility for the effects.
The research showed that the antibody didn't prevent the loss of myelin in an animal model, but it did reduce the effects of disease progression.
Though the development is clearly exciting, the antibody is only in toxicity studies that are expected to be completed later this year. Biogen expects to file an Investigational New Drug application with Food and Drug Administration in the fourth quarter and begin human studies starting shortly thereafter.
Rhodes noted that the next goal is to conduct proof-of-concept studies to determine if the drug inhibits LINGO function in humans with the same positive effects.
The possibility of repairing damage done by MS and reducing symptoms of the disease would be revolutionary for MS patients, but Dr. Richert believes that currently used therapies are likely to continue as the best treatment for new patients who may not have a lot of nerve damage.
Regeneration would be used on patients who already have neurological deficits, he said, as well as those whose disease continues to progress regardless of treatment.
In order to provide the best benefit, Dr. Rhodes said that the anti-LINGO antibody would likely be used in combination with one of the more traditional immunosupressive approaches.
"As you dampen the immune response, you treat with anti-LINGO to try and actually facilitate recovery and repair," he said.
If successful, the antibody could have a future in treating other neurological disease such as Parkinson's, or even help repair damage done to the spinal cord.
Biogen has a number of programs to explore the antibody's use in other diseases but is cautious on any of those prospects.
"The preclinical data supporting the utility of those indications isn't as well developed yet as it is with MS," Dr. Rhodes said.
Source: CNN Money.com © 2009 BigCharts.com Inc. (14/01/09)Submitted 1/27/2009 5:34:43 PM