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MS Society funded study identifies antipsychotic drug as potential therapy for progressive MS

  • Canadian Study
  • MS Society Funded

Background:

Developing a new drug is a complex process involving an enormous amount of time, money and effort. Taking basic research findings about a disease like MS, and translating them into viable, safe, and effective therapies can take decades, and even after that there are still additional regulatory check-points that need to be passed before people can access medication. It is critical to advance strategies that will reduce this time frame while decreasing costs and ensuring that the drug remains effective.

One approach that researchers and industry players have taken is to survey currently available drugs and look for biological characteristics that may be beneficial in another disease. This process is called drug repurposing, and bears significant advantage over traditional drug development as the therapy has already passed preliminary safety tests that would otherwise take up valuable time and resources.

Drug repurposing and MS:

Currently there are a number of drugs, originally indicated for specific conditions, which may be useful in treating MS.

Amiloride (Midamor) – An oral blood pressure medication that has shown neuroprotective effects in mice with MS-like disease. This led to the first human trials led by a research team in the UK. Results of the pilot trial showed that treatment with amiloride resulted in a reduction in brain shrinkage in people with primary progressive MS.

MN-166 (Ibudilast) – This anti-inflammatory drug has been widely used in Japan and Korea to treat post-stroke complications and asthma. In early trials with MS patients, Ibudilast was unable to reduce new disease activity, but showed other benefits such as a decrease in brain volume loss. A newly approved trail is set to launch in the US to determine the safety, tolerability and activity of Ibudilast in people with progressive MS. Details of the trial can be found here.

MS-Society funded researchers identify another potential treatment for MS:

Last month, MS Society funded-postdoctoral fellow Simon Zhornitsky from the University of Calgary published a review in the journal CNS Neuroscience & Therapeutics on an antipsychotic drug that has the potential to treat MS, specifically progressive MS. The drug is called quetiapine fumarate, and it has previously shown benefits in conditions such as mood disorders, pain disorders, anxiety and insomnia.

More recently, quetiapine fumarate - marketed as Seroquel - has demonstrated remyelinating and neuroprotective capabilities in mice with MS-like disease, making it an attractive candidate for future treatment. According to the article, remyelination and neuroprotection are the next frontiers of MS therapy, and as such significant research activity is now being directed towards these areas.

What is remyelination and neuroprotection?

Remyelination: During an MS attack, immune cells enter the central nervous system and cause inflammatory damage to myelin, which surrounds and protects nerve cells. Without myelin, the structure and function of the nerve cells are severely compromised. Studies show that there is some degree of recovery, during which new myelin re-forms around the nerve cells. This process is referred to as remyelination. Remyelination is critical in preventing further damage to the nerves and allow the nerves to maintain the necessary communications required to direct functions like seeing, walking, speaking and thinking.

Neuroprotection: In some cases myelin cannot be rebuilt, and the exposed nerves are suddenly prone to deterioration which could have grave consequences. Protecting the nerves is critical in managing MS, as it could be the most important step in preventing transition from relapsing-remitting MS to progressive MS, or preventing someone from acquiring progressive MS from the start. This process – referred to as neuroprotection – is crucial in keeping nerves healthy and stopping degeneration of the tissues in the brain and spinal cord.

Quetiapine Fumarate and MS:

In recent studies, quetiapine fumarate was shown to promote remyelination and reduce damage to neurons in mice with MS-like disease. In one pivotal study, researchers created a condition in mice resembling progressive MS, which he refers to “chronic demyelination”. They separated the mice into two groups: one received quetiapine fumarate for 5 weeks, and the other did not. The group that was given quetiapine showed significantly less myelin breakdown, while the other group exhibited ongoing breakdown of myelin throughout the brain. The same study also demonstrated that administration of quetiapine fumarate led to recruitment of young brain cells, and stimulated those cells to become oligodendrocytes – the cells which produce myelin.

The review goes on to describe the immunomodulatory properties of quetiapine fumarate. This means that the drug can control the activity of cells in the immune system. One study revealed that, in mice with MS-like disease, quetiapine fumarate dampened the activity of T-cells and other harmful immune culprits of MS.

In addition to its remyelination, neuroprotective, and immunomodulatory qualities, quetiapine fumarate may be valuable in treating MS due to its other well-documented benefits. The review eloquently describes the lines of evidence which demonstrate the drug’s ability to mitigate many of the symptoms and co-existing health conditions associated with MS, including depression, anxiety, sleep disturbance, headaches and pain.

Mechanisms of Action:

It is thought that this quetiapine can enhance the repair of myelin and maintain the structural integrity of nerve cells by stimulating the growth and development of myelin-producing oligodendrocytes and increasing antioxidant activity. Furthermore, quetiapine has been shown to control the expression of genes which are important to the survival, development and function of nerve cells.

Future Work:

Dr. Zhornitsky emphasized the need for therapies that jumpstart the remyelination process following immune attacks on the nervous system. With a small list of agents available to do this, research into new treatment avenues as well as looking to other available drugs that can induce myelin repair and slow the progression of MS are moving up the priority list.

“Research is shifting focus to promoting remyelination (myelin repair) in MS. We can start by creating new knowledge about the biological basis of remyelination and by evaluating new therapies to promote remyelination in mice. Ultimately, the goal is to test such therapies in people with MS.”

Dr. Zhornitsky is hopeful that preliminary research in this area will lead to better treatments for people with all forms of MS as well as improved tools for measuring myelin repair.

“We now have one candidate medication (quetiapine fumarate) that could provide a new avenue for promoting repair in both relapsing-remitting and progressive MS patients. The resulting data will also help to further evaluate and improve cutting-edge magnetic resonance imaging (MRI) techniques in their ability to detect and measure remyelination in MS patients.”

The MS Society of Canada is currently funding Dr. Zhornitsky’s work in this area, which has and will continue to provide the groundwork to conduct future clinical trials. These trials will determine the safety and tolerability of quetiapine in people with MS, as well as examine the ability for this drug to stimulate myelin repair in humans. If the remyelination effects of quetiapine – which already been seen repeatedly in mice – are evident in humans, this drug may be used to treat both relapsing-remitting and progressive MS in the future.


Sources:

Zhornitsky S et al. Quetiapine fumarate for the treatment of multiple sclerosis: focus on myelin repair. CNS Neuroscience and Therapeutics 2013;19(10):737-44.

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