MALDI imaging mass spectrometry scans show the broad distribution of clozapine (upper right image) compared to other molecules that show brain-region localisation (lower images).

Research Report 2016 - Multiple sclerosis

16 January 2017, Multiple Sclerosis

Professor Anne La Flamme from Victoria University’s School of Biological Sciences leads the Malaghan Institute’s multiple sclerosis (MS) research programme. This research is investigating the underlying mechanisms of the chronic autoimmune disease as well as developing treatments for its progressive forms.

A Phase Ib/IIa suitability and acceptability trial of two antipsychotic medicines, clozapine and risperidone, repurposed to treat MS, has now begun. The trial received funding from the Ministry of Business, Innovation and Employment’s High Value Manufacturing and Services Research Fund and support from the Great New Zealand Trek. Recent research has shown that the drugs act on the immune system and reduce inflammation associated with MS, at much lower doses than are required for treating schizophrenia and bipolar disorder.

The 36-person trial compares clozapine and risperidone and assesses their clinical effects in treating progressive MS. The most suitable medicine of the two will then be selected to progress. Another aspect of the research is identifying the mode of action and pathway by which the drugs reduce the disease.

“We don’t know which drug will be better, but the primary objective is to make sure that it does not have any negative consequences. People on the trial have significant long-term disability and we don’t want to add to that. It may be that treating this population with the drugs is no different to any other population, but until you do it you can’t be sure,” says Professor La Flamme.

Preliminary studies of the drugs’ mode of action reveal that they are reaching and acting on the brain as intended. In an animal model of the disease, MALDI imaging mass spectrometry is being used to track clozapine to different parts of the brain, as well as other tissues, to identify the sites of action.

“We’ve found no dramatic effects on the immune system outside the brain, which is very heartening. We’re seeing most of the effects in the central nervous system, which is what we want – and what we would expect of the drugs. The research is helping us understand the immune response and how we’ve altered the immune system.”

Professor La Flamme would like to acknowledge and thank the Great New Zealand Trek for their support of MS research, including the patient-related costs of the trial. “We would not have been able to even start the trial without the Trek – they have been with us for the long run. Since the beginning, they have supported our research programme with more than $200,000.”

Another organisation, Trekking Events, is supporting research into how clozapine and risperidone are altering the immune response in trial participants. “By looking at changes in their blood samples over time, we can understand how people are responding to the drugs and perhaps find a marker for a good response to them.”

Research team

Professor Anne La Flamme

Carl Beyers, Faith Leonard, Dr Katharina Robichon, Nikki Templeton, Dr Jenni Williams, Pirooz Zareie