Promising New Treatments for Multiple Sclerosis

New treatments for multiple sclerosis (MS) using common anti-psychotic agents have been discovered by Victoria University of Wellington researchers.

The study led by Dr Anne La Flamme, an associate professor in the School of Biological Sciences and head of the MS research programme at the Malaghan Institute of Medical Research, based at Victoria, shows the potential of clozapine and risperidone to effectively treat MS.

MS, a neurological disease which affects one in every 1,400 New Zealanders, is caused by immune cells invading the brain and causing inflammation. It leads to impaired vision and coordination and, eventually, paralysis, explains Dr La Flamme.

“While disease-modifying drugs are currently available, they are often effective in only a subpopulation of MS patients and all of these treatments target the disease through traditional immune pathways,” she says.

The image shows stained slices from the experiment.

Iba-1 expression (deep pink) in the cerebellum was assessed by immunohistochemistry and counterstained with hematoxylin (light purple). Shown are representative sections from unimmunized and immunized, vehicle and risperidone-treated mice as well as the “Iba-1 score” and “disease score” at time of euthanasia. Credit La Flamme et al./PLOS ONE.

“What makes our findings so important is that clozapine and risperidone target a very different set of pathways from all other MS drugs, and thus have the potential to treat those MS populations for which no effective therapies currently exist.”

Published this week by international scientific journal PLOS ONE, the study demonstrates that risperidone and clozapine can reduce MS significantly by reducing the inflammation in the brain that causes this disease.

Additionally, this research indicates that the way clozapine and risperidone improve disease outcomes in MS is different from how these agents work to treat mental health disorders.

“By utilising existing therapies, this work may more quickly support improved outcomes for people with MS,” says Dr La Flamme.

Notes about this Multiple Sclerosis research

This study, funded by the Neurological Foundation of New Zealand, was undertaken in collaboration with Dr Bronwen Connor, an associate professor at the University of Auckland.

Source: Communications Department – Victoria University of Wellington
Contact: Victoria University of Wellington press release
Image Source: The image is credited to La Flamme et al./PLOS ONE and is adapted from the open access research paper
Original Research: Full open access research for “Treatment with the Antipsychotic Agent, Risperidone, Reduces Disease Severity in Experimental Autoimmune Encephalomyelitis” by David O’Sullivan, Laura Green, Sarrabeth Stone, Pirooz Zareie, Marie Kharkrang, Dahna Fong, Bronwen Connor, and Anne Camille La Flamme in PLOS ONE. Published online August 12 2014 doi:10.1371/journal.pone.0104430

Open Access Neuroscience Abstract

Treatment with the Antipsychotic Agent, Risperidone, Reduces Disease Severity in Experimental Autoimmune Encephalomyelitis

Recent studies have demonstrated that atypical antipsychotic agents, which are known to antagonize dopamine D2 and serotonin 5-HT2a receptors, have immunomodulatory properties. Given the potential of these drugs to modulate the immune system both peripherally and within the central nervous system, we investigated the ability of the atypical anti-psychotic agent, risperidone, to modify disease in the animal model of multiple sclerosis (MS)4, experimental autoimune encephalomyelitis (EAE). We found that chronic oral administration of risperidone dose-dependently reduced the severity of disease and decreased both the size and number of spinal cord lesions. Furthermore, risperidone treatment substantially reduced antigen-specific interleukin (IL)-17a, IL-2, and IL-4 but not interferon (IFN)-γ production by splenocytes at peak disease and using an in vitro model, we show that treatment of macrophages with risperidone alters their ability to bias naïve T cells. Another atypical antipsychotic agent, clozapine, showed a similar ability to modify macrophages in vitro and to reduce disease in the EAE model but this effect was not due to antagonism of the type 1 or type 2 dopamine receptors alone. Finally, we found that while risperidone treatment had little effect on the in vivo activation of splenic macrophages during EAE, it significantly reduced the activation of microglia and macrophages in the central nervous system. Together these studies indicate that atypical antipsychotic agents like risperidone are effective immunomodulatory agents with the potential to treat immune-mediated diseases such as MS.

“Treatment with the Antipsychotic Agent, Risperidone, Reduces Disease Severity in Experimental Autoimmune Encephalomyelitis” by David O’Sullivan, Laura Green, Sarrabeth Stone, Pirooz Zareie, Marie Kharkrang, Dahna Fong, Bronwen Connor, and Anne Camille La Flamme in PLOS ONE. doi:10.1371/journal.pone.0104430

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