November 23, 2001
by David Leidl
Multiple sclerosis is a vampire disease. Once it fastens onto a victim, it can’t be shaken free. Slowly, it drains the victim of vitality, of movement. But it might soon be on the run.
Researchers at Stanford University Medical Center and the University of California San Francisco have keyed onto a critical gene that could be the driving factor behind the disease’s progression. Previously, the osteopontin gene had been fingered as a factor in the inflammatory immune response characteristic of MS.
MS is thought to be an auto-immune disease that leaches the nervous system, inflaming the protective ‘insulation’ – the myelin – that covers nerve cell axons. This patchy loss of myelin in the brain and spinal cord slows the communication between nerve cells, leading to muscle spasms, weakness, sensory deficits and visual disturbances.
Long thought to be an ‘adult’ disease, it’s most commonly diagnosed between the ages of 10 to 15 years. MS takes years to take hold. . . but it does. Bedridden, entombed in a body that no longer functions properly, the MS victim slowly fades. All she can do – two out of three MS victims are women – is wait for her body’s core functions to flicker and fail.
The afortementioned new research into the osteopontin gene now suggests that osteopontin is much more involved, a sort of triggerman that ushers MS through the various checkpoints of the disease’s progression
The hope: trip up the gene and you stall the disease.
Multiple sclerosis and osteopontin, vampire and gunsel. The mixed analogy works, especially as the motivator behind the Sanford/UCSF study is what Sanford professor of neurology Dr. Larry Steinman calls "the genomic application of ‘Sutton’s Law’." Sutton was a successful (if short-lived) bank robber who was asked why he robbed banks. His laconic reply: "Because that’s where the money is."
In this case, the ‘bank vault’ is the human skull, the ‘money’ was the autopsied brains of MS patients. Or as Dr. Steinman put it, the study was "a direct extension of a 10-year adventure" which examined a lot of tissue and tracked the gene expression in the inflamed MS brain during the course of the disease. The trick: find the genetic culprit. For Dr. Steinman and Dr. Jorge Oksenberg, associate professor of neurology at UCSF, the chase was long and hard.
In a paper in the November 23, 2001 issue of Science, senior co-authors Drs. Steinman, Oksenber and Renu Heller say that, thanks to large-scale sequencing analyzed by Dr. Sergio Baranzini at UCSF, the researchers might have smoked out the bad guy.
To do that, the researchers first created a comprehensive gene library from the autopsied tissue. Then they hunted for genes that popped up most often in MS brains vis-a-vis normal tissue. . . and osteopontin kept appearing in "abundance," says Steinman.
But being spotted loitering around a bank heist doesn’t necessarily mean you’re involved. To get the goods on osteopontin, researchers first determined that osteopontin ‘expression’ (i.e. a gene’s bio-chemical influence) varies with the phase of the disease. In animal studies overseen by Dr. Dorthee Chabas at Stanford, rodents were induced with an autoimmune disease similar to MS in humans. Two important clues emerged:
Osteopontin expression was most prominent in nerve cells near active MS-like lesions during the acute and relapse stages of the disease but not during remission. In other words, this genetic bystander was somehow indeed involved.
Secondly, by inducing the MS-like disease in genetically altered mice lacking osteopontin, the researchers confirmed that osteopontin does indeed affect the course of the disease.
The mice that lacked osteopontin demonstrated disease manifestations "significantly less severe" than those suffered by the control group. As well, the percentage of remissions was much higher in the osteopontin-deficient mice and there were no disease-related deaths.
In other words, the new research suggests that osteopontin may influence the evolution of the disease, determining whether relapses and remissions develop. In other words, osteopontin is more than just a innocent bystander. It’s part of the heist, it has a gun and doesn’t seem afraid to use it.
"With this finding, a major piece of the puzzle is in place," says Oksenberg, "but there is much more work to be done." Indeed. Steinman adds that in addition to the osteopontin gene, a number of other MS suspects have been identified and warrant a detailed slap-around and genetic grilling.
For the 350,000 Americans and 2.5 million MS sufferers worldwide, the news is hopeful. For small-cap biotechs now shouldering into the MS market, a market which is worth more than $1 billion in the United States alone, the thought of a new genetic therapy is interesting indeed.
Meanwhile, the main contenders in the MS arena are selling their own wares. Biogen (NASDAQ: BGEN), Chiron (NASDAQ: CHIR) and Serono SA (NYSE: SRA) and Elan Corporation (NYSE: ELN) are all big caps and all have product in the market.
In the small caps, the R& D soldiers on. The contenders include: AVANT Immunotherapeutics, Inc. (NASDAQ: AVAN); AutoImmune Inc. (NASDAQ: AIMM) and Neurocrine Biosciences Inc. (NASDAQ: NBIX)
Smallcapcenter.com’s advanced research department gave AVAN a signal stockscore of 52 at 1:53 p.m. EDT on Friday. AIMM received a stockscore of 68 and NBIX received a score of 76.
A company’s stockscore is an unbiased summary of numerous technical analysis indicators like volume and momentum, which are combined to produce a value on a scale of 1-100 with 100 being the highest level.