March 9, 2015

Researchers take new approach to help MS patients

University scientists use futility trials in search for drugs to fight common form of disease
Marcus Koch leads a team of researchers from the Hotchkiss Brain Institute in a fresh approach to identifying drugs to fight the secondary progressive form of multiple sclerosis.

Marcus Koch leads a team of researchers from the Hotchkiss Brain Institute.

Riley Brandt, University of Calgary

Scientists from the University of Calgary’s Hotchkiss Brain Institute (HBI) hope to trim years off the hunt for a way to help people suffering from a common type of multiple sclerosis (MS) that is currently untreatable.

A team led by Dr. Marcus Koch is introducing a fresh approach to finding drugs to fight the secondary progressive form of the disease. Building on earlier HBI research at the university’s Cumming School of Medicine, he plans to speed things up by using a new model for phase II studies called futility trials.

“They have been used in other fields of medicine, but they haven’t been done before in MS,” says Koch, who is a member of HBI’s MS NeuroTeam and an Alberta Health Services neurologist at the Calgary MS Clinic. Futility trials are simpler than the usual randomized studies, he says, adding that testing will be further quickened by using drugs already approved as safe for humans.

Search for a drug to help secondary progressive form of MS

By damaging nerve cells in the brain and spinal cord, MS affects about 100,000 Canadians, causing everything from fatigue to an inability to walk independently. It mostly first strikes people ages 20 to 40 at the height of their productive lives, says Koch, who is also an assistant professor at the university’s departments of Clinical Neurosciences and Community Health Sciences.

The majority of MS cases begin with the relapsing-remitting form of the disease, which features attacks followed by periods of varying recovery, he says. While scientists haven’t found a cure for this type of MS, they have discovered drugs that can help reduce or even prevent attacks. But the drugs don’t work on the secondary progressive form of the disease, which eventually afflicts the vast majority of those with relapsing-remitting MS, says Koch.

“In general, with secondary progressive MS, you gradually become able to do less and less,” he says. “You can’t walk as far as you once did, then eventually, you might only do that with a walker, and then you might need a wheelchair. It’s devastating, because if you keep seeing that progression, you know it’s going to keep getting worse. Ultimately, people may need to be looked after in a long-term care facility. They can die of complications such as pneumonia.”

Domperidone at centre of futility trial

Scientists usually try to treat secondary progressive MS by using drugs that work in the relapsing-remitting form, an approach that has so far been unsuccessful, says Koch. His team is instead using a futility trial on one group of 62 people, who will be tested for their ability to walk 25 feet. They will be given daily doses of domperidone, which has been approved in Canada to prevent nausea and is widely used in people with Parkinson’s disease or diabetes.

An interesting effect of domperidone is its ability to boost the production of prolactin — a hormone that researchers at the HBI have shown can improve the repair of myelin. Much of the damage from secondary progressive MS is due to the deterioration of myelin, which insulates nerve cells. While Koch doesn’t expect domperidone to be a cure, he hopes it will help slow the progression of the disease.

Participants for the trial are being chosen from patients at the Calgary MS Clinic of Alberta Health Services. As they join the study, they will be followed and tested for a year. If domperidone doesn’t have any significant effect, researchers will move on to test other drugs.

Framework of trial speeds testing

“The futility model framework gives us the chance to test drugs more quickly and efficiently than in classical randomized controlled trials,” says Koch. “This is advantageous, as there are a number of generic drugs that we suspect can impact disease progression in secondary progressive MS.” Drugs that appear promising in a short futility trial will still need to be tested in randomized controlled trials, but this model will allow more rapid selection of the most promising therapies.

Koch is also launching a separate outcome study for people too disabled to be in the futility trial. It will track the deterioration of patients who are already unable to walk, and those with primary as well as secondary progressive MS over two years, potentially laying the groundwork for inclusion of more patients in further trials for new treatments.

The studies are being funded by Alberta Innovates-Health Solutions’ CRIO Team program on Remyelination.

Led by the Hotchkiss Brain Institute, Brain and Mental Health is one of six strategic research themes guiding the University of Calgary toward its Eyes High goals.