At a glance:
In recent years there has been considerable advancements in treating the most common form of MS – relapsing-remitting MS. Unfortunately, for people with progressive forms of MS, both primary and secondary, there have not been such advances. Trials testing the current treatments for relapsing MS in people with progressive MS have not worked, with the recent exception of Ocrevus, which (has recently been approved by a number of countries as a progressive MS treatment).
A possible explanation for this is that the underlying mechanisms of progressive MS is likely very different to those in the relapsing-remitting form of MS. Progressive MS displays less involvement of the immune system, but has more degeneration of nerve cells.
In an effort to find a new treatment for progressive MS, a group of Canadian scientists have screened 249 medications which are already in use to treat other diseases to see if they could influence some of the underlying mechanisms of progressive MS. This is known as drug repurposing, or drug repositioning, where a known drug is used to treat a different disease. The advantage of drug repurposing is that the drug has usually already passed safety tests and so may pass through the clinical trials and regulatory approval processes more quickly.
This study has been recently published in the highly prestigious Nature Communications journal.
The scientists started out with 1040 medications and first ruled out all the medications which couldn’t be taken orally and couldn’t cross the blood brain barrier. That reduced the number to 249. They then tested the 249 medications for their ability to protect neurons against a range of damaging scenarios. From this they identified 14 medications which could protect neurons and further reduced that to four after further testing. They then looked at whether these four medications could influence certain immune cells involved in progressive MS. This narrowed the list down to just one medication – an antidepressant called clomipramine.
The research team were then able to take this most promising candidate forward into the more complex and expensive experiments needed to assess if clomipramine could slow disease progression.
To test this they used mice with two different types of progressive MS-like disease. In both models clomipramine was able to reduce the clinical severity of the disease including reducing disability progression. Their results suggested that this may be due to a reduction in the number and activity of immune cells moving into the brain and spinal cord. There was also less degeneration of nerve cells in the animals treated with clomipramine.
This study is exciting because it not only identified a possible medication that might be beneficial for people with progressive forms of MS, but it also demonstrates a really thorough and systematic approach that could be used to screen other large panels of medications to identify drugs that could be repurposed for progressive MS.
While this research hasn’t reached the clinical trial stage yet, the advantage of testing known compounds is that they can be more rapidly translated from the laboratory into clinical trials.