In recent years, there have been considerable advancements in treating the most common form of MS: relapsing remitting. However, for people with progressive forms of MS (both primary and secondary), advances have been limited. For the most part, trials that have tested current treatments for relapsing MS in people with progressive MS have been unsuccessful, with the exception of Ocrevus, a drug recently approved by a number of countries for the treatment of progressive MS.
A possible explanation for this is that the underlying mechanisms of progressive MS are thought to be very different to those in the relapsing remitting form of MS; progressive MS displays less involvement of the immune system, but involves greater degeneration of nerve cells.
In an effort to find a new treatment for progressive MS, a group of Canadian scientists have screened 249 medications that are already used 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’, in which 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 may therefore pass through the clinical trials and regulatory approval processes more quickly.
In this study, recently published in the prestigious Nature Communications journal, the scientists started out with 1040 medications. They then ruled out all of the medications that cannot be administered orally and cannot cross the blood brain barrier, which reduced the total number to 249. Next, the team tested the ability of these 249 medications to protect neurons against a range of damaging scenarios. From this process, they identified 14 medications that could protect neurons and, after further testing, reduced this to four medications. The next step was to identify whether these four medications could influence certain immune cells that are involved in progressive MS. This narrowed the list down to just one medication: an antidepressant called clomipramine.
The research team was then able to take this promising candidate forward into the more complex and expensive experiments required to assess whether clomipramine could slow disease progression.
To test this, the scientists 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 the reduction of 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; not only has it identified a possible medication that might be beneficial for people with progressive forms of MS, but it has also demonstrated a thorough and systematic approach that could be used to screen other large panels of medications and identify drugs that could be repurposed for progressive MS.
Whilst this research has not yet reached the clinical trial stage, the fact that it involves the testing of known compounds means that these can be more rapidly translated from the laboratory into clinical trials.
With thanks to MS Research Australia – the lead provider of research summaries on our website.