I have seen the invisible arms of multiple sclerosis, a potentially devastating disease of the nervous system, touch friends, relatives and acquaintances. They perturbed the personality of a father of a close friend and left him unable to keep a job and support the family. They forced a young woman I met years ago to walk tentatively, watching her step. They put one beloved member of my extended family with two small children in a wheelchair and took away his voice.
Nowadays, many people with MS find that new medications can mitigate the progression of their disease (see “New Treatments Tackle Multiple Sclerosis,” by James D. Bowen, Scientific American Mind, July/August 2013). But many mysteries remain about the cause of the disorder and no one knows how to prevent or cure it. About a decade ago, a technology entrepreneur named Art Mellor, who was diagnosed with MS in 2000, founded an organization called Accelerated Cure Project based in Waltham, Massachusetts to help speed progress on solving these mysteries, in part through greater collaboration among scientists. In one of its efforts, it maintains a repository of thousands of blood samples from patients who visited any of 10 U.S. clinics. The samples are made available to anyone willing to share their data with the Project. Scientists have used these samples in more than 70 different studies into the causes of MS and how to diagnose and treat it.
A number of these experiments involve trying to identify molecular signs of the disease in the blood, in hopes of developing a simple blood test for the disorder. Such a test might reduce the time and cost of an MS diagnosis. The primary tool for spotting MS today is magnetic resonance imaging (MRI), which can reveal inflammation in the brain characteristic of the disorder. (Most people believe that multiple sclerosis is an autoimmune disorder—a product of an aberrant immune response directed against the body’s own nerves.) But MRI is expensive. It is also not definitive. Sometimes a spot that looks like MS on a brain scan is caused by another condition such as diabetes. Conversely, a normal MRI does not rule out the disorder. Often, too, a doctor has to repeat the scan, and even wait for more symptoms to appear, delaying the diagnosis, sometimes for years.
Doctors also may do a spinal tap, in which they sample the cerebrospinal fluid and examine it for the presence of an immune system protein that should not be there. Electrical tests of nerve function can provide further hints that MS is present. But these tests are not foolproof either and spinal taps are invasive. “For an autoimmune disease, no test is specific or accurate, so you try to build a case for a diagnosis,” says Thomas M. Aune, a molecular biologist at Vanderbilt University School of Medicine.
In building that case, physicians would also like to have a blood test, says Aune, because drawing blood is quick, inexpensive and relatively noninvasive. To develop the basis for such a test, Aune and his colleagues used samples from the Accelerated Cure Project to look for systematic differences between blood from individuals with and without the disease. Aune’s team analyzed the samples using a tool called a microarray, which measures the levels of molecular readouts, or transcripts in the form of messenger RNA, from a large set of genes. The result is a so-called gene expression pattern. The scientists saw discernable differences between the pattern formed by a set of 31 genes in MS patients and the same set from individuals without the disease. (These candidates were culled from a larger set of several thousand genes whose expression patterns Aune’s team had previously associated with autoimmune disease in general.)
The results suggest that doctors could analyze blood for readouts from these genes to determine whether or not an individual has MS. Aune’s work so far suggests that the test identifies true cases of MS more than 90 percent of the time and has a similar success rate in ruling out the disease in patients who don’t have it. “We can compare MS patients to controls and to patients with other neurological disorders and easily split them apart from both,” Aune says. In a follow-up study, as yet unpublished, the researchers matched unique gene expression profiles to different stages of MS, suggesting that his test may also reveal how far the disease has progressed in an individual.
One blood test for MS is already commercially available. The so-called gMSDx test, developed by a company called Glycominds based in Simi Valley, California, picks up antibodies (immune system proteins) directed at a sugar molecule called a-glucose antigen GAGA4. Such antibodies are often present at high levels in MS patients. A positive result—that is, a high concentration of these antibodies—can help solidify a diagnosis in patients with MS-like symptoms, but whose brain scans are not definitive. It thus can reduce the number of scans needed before deciding whether or not the disease is present.
Vanderbilt University has licensed Aune’s genetic blood assay to Iverson Genetics, a small diagnostics company based in Bothell, Washington. The company will oversee studies using larger sample sizes as a first step in developing a commercial test. If and when this test becomes widely available, it would not be definitive on its own. Aune envisions it as a way to decide if a patient who complains of, say, nonspecific numbness, really needs an MRI. Like the Glycominds test, it could also speed a diagnostic decision down the road. Both applications would greatly benefit people waiting to find out what is wrong with them. Those who do not have MS should not be put on potentially toxic treatments for that condition, and may need treatment for something else. Those who do have the disease ought to get appropriate medication ASAP. “If you could treat people with MS earlier, then you could delay the development of long-term disability and may make the overall course of the disease better,” Aune says.
Ultimately, Aune hopes these genes will point beyond diagnosis to a new understanding of how MS develops—an essential step to better treatments. Accelerated Cure has played no small part in this progress. “Working with them allowed us to obtain critical samples and confirm our results for only $20,000,” Aune says. “If I had to obtain these samples from scratch, it would have cost $1 million and added 5 years to the project.”