The GlycoChip can analyze blood samples of multiple sclerosis patients to determine the level of severity of the disease.Multiple sclerosis (MS) affects some 400,000 Americans and is the most common neurological disorder diagnosed in young adults. MS affects eyesight, mobility, bladder and bowel control, and causes chronic pain and dizziness.
A quarter of those diagnosed with MS may actually have a benign form, meaning they won’t have any symptoms for at least 10 years. Currently, however, there is no method of determining who has this benign form. The result: Many people, diagnosed with MS, are taking medication they don’t yet need, with all the attendant side-effects, as well as suffering from excessive anxiety.
There is also no way to determine who has the most severe form of the disease – approximately 20 percent of MS sufferers. If this could be diagnosed at the outset, these people could get the most aggressive treatment available.
Now, an Israeli company, Glycominds, has a simple blood test that could solve this problem by distinguishing between mild and more severe cases of MS early on. Clinical trials of the new test are about to begin across the US and Canada.
“The problem is not with diagnosing the disease,” says Glycominds’ chief executive, Avinoam Dukler. “Multiple sclerosis is diagnosed with an MRI test [after the patient has presented symptoms]. The major problem is distinguishing between the different active forms of the disease.” This ranges from benign to moderate to the most severe form, where a patient will probably be wheelchair-bound only two years after the initial diagnosis.
“Currently, physicians can’t tell which form a patient has until afterwards. [If they could], the way to treat these patients would vary,” says Dukler. Currently, each patient is treated alike: after initial diagnosis all are started on medication.
Glycominds wants to give the doctor more options. The Lod-based company’s field of expertise is glycomics – that is the behavior of glycans, the sugars that are present in and on the surface of human cells. Genes give instructions to the proteins, but it is the glycans that guide the proteins to their targets and makes sure they do what they are supposed to do.
“We have identified a specific antibody, which goes into action when a foreign body enters the body, and is present in high levels in people with multiple sclerosis,” says Dukler. Tests showed that this is not something common to all those with neurological disorders, but specific to MS. “More active forms [of MS] have a much higher level of [this] antibody than others.” This is known as a ‘biomarker’ for a specific disease.
A simple blood test using Glycominds’ MS GlycoChip, a microscope-slide-sized ‘biochip’ for testing reactions of glycans with other molecules, to measure the level of this antibody could help doctors decide what treatment, if any, to prescribe. The doctor takes a blood sample using the Glycominds kit, and then sends it to a laboratory for analysis.
Glycominds is just completing the protocol design for clinical trials of the blood test at 80 multiple sclerosis centers across the US, Canada and Israel. Taking part will be patients whose condition is called ‘clinically isolated syndrome’ or CIS: they have had one presentation of symptoms and an MRI shows signs that there is a very high probability that they have MS, but they have not yet begun treatment. The trials, which are due to commence at the beginning of 2005, will include 385 patients, and will be the largest ever trial of CIS patients.
After the first year of recruiting participants, the trial will consist of several six-month “windows”. “We will predict, from taking blood samples at the first presentation [of symptoms], when the next presentation will be: Will it be within six months, yes or no?” explains Dukler. “This should reduce patient anxiety and enable the physician to make a decision [regarding the most appropriate treatment].” If the blood test predicts there will be no symptoms within the next six months, the physician can advise the patient not to start taking medication yet. After six months, the patient takes another blood test.
The trial is scheduled to continue until 2008. If, however, all goes according to plan and results after the first six-month period, in 2006, prove that the blood test is indeed an accurate predictor of a patient’s condition, Glycominds will be ready to start marketing the product.
The multiple sclerosis market is estimated to be worth around $4 billion, notes Dukler.
Glycominds is not limiting its efforts to multiple sclerosis. The company is also looking at developing biomarkers to enable more accurate diagnosis of inflammatory bowel disease, which affects about a million people in the US alone. Within this category are Crohn’s disease and ulcerative colitis, which have very similar symptoms, but require completely different treatment: The surgery that can be used to treat ulcerative colitis can pose risks for a sufferer of Crohn’s disease.
“We have found antibodies for Crohn’s disease,” says Dukler. “Currently none of the diagnostic methods is considered a ‘gold standard’. They are complex and long and expensive procedures.” Glycominds has developed a blood test, which took an existing biomarker and added two more that Glycominds discovered, which recognizes over 80 percent of those with Crohn’s disease. One of these biomarkers can recognize a subset of patients who have Crohn’s disease in the colon.
“We have already validated the test for distinguishing between Crohn’s and ulcerative colitis, and we are going to launch a product in Europe at the beginning of 2005,” says Dukler, noting that it too will be a kit which doctors use to take blood samples which are then sent to a laboratory. The company is continuing to develop further tests for diagnosing Crohn?s disease in the colon and for distinguishing patients with irritable bowel syndrome from those with inflammatory bowel disease.
Glycominds is also looking further afield. “The GlyoChip platform has the ability to identify many other biomarkers,” says Dukler. “Inflammatory and autoimmune diseases [like multiple sclerosis] are the initial focus of the company, but it is not limited to that. Glycans play a critical role in many indications.”