While people with relapsing-remitting multiple sclerosis (MS) are getting assistance from successful studies and new treatments, those with progressive MS may feel they’re less likely to find help.
But a new study out of Canada has made two major discoveries to help end this pattern.
The first is a clinical way to measure currently approved oral generic drugs that benefit people with MS in a timely manner.
The second is to further study the benefits of the antidepressant clomipramine as a potential therapy for progressive MS.
According to the study, in order to successfully treat progressive MS, the treatment should simultaneously target three MS disease drivers.
These drivers include iron-mediated neurotoxicity, lymphocyte activity, and oxidative stress.
What the study uncovered
The study looked at generic, orally available medicines that target the three drivers of progressive MS.
A successful drug must be able to cross the blood-brain barrier and have a positive effect on all three disease drivers.
Out of the initial 1,040 drugs tested, 249 were able to cross this barrier. Of these, 35 prevented iron-mediated neurotoxicity in culture.
This list was further narrowed down based on how the drugs managed the remaining two disease drivers.
Among the semifinalists were several antipsychotics and antidepressants.
One antidepressant that stood out was clomipramine. It also showed the ability to inhibit lymphocyte activity.
In addition, clomipramine is a well-tolerated antidepressant.
What is clomipramine?
Discovered in 1964, clomipramine has been used to treat obsessive-compulsive disorder, panic disorder, major depressive disorder, and chronic pain.
It’s on the World Health Organization’s Model List of Essential Medicines, considered to be the most effective and safe medicines needed in a health system.
Common side effects include constipation, dry mouth, loss of appetite, sleepiness, sexual dysfunction, trouble urinating, and weight gain.
It also runs a risk of affecting the liver. This could interfere with some MS disease-modifying therapies.
In some cases, the risk of suicide increases, around 25 years of age. The drug may also not be safe during pregnancy.
More testing is needed.
Clomipramine works by reducing inflammation and microglial activation.
The human body manages inflammation by activated microglia. These are the immune cells of the central nervous system.
The microglia respond to neuronal damage and remove the damaged cells by phagocytosis — a fancy word for a Pac-Man sort of behavior where one cell engulfs another.
Of mice and humans
The study also looked at clomipramine in mice, specifically those with autoimmune encephalomyelitis, which is considered a model for MS.
In mice, clomipramine significantly improved the clinical signs of acute and chronic phases of MS.
“This is an interesting approach of ‘repurposing’ old drugs for new uses,” explained Dr. Barbara Giesser, professor of clinical neurology at the David Geffen School of Medicine at UCLA and clinical director of the UCLA MS program.
“The animal results are very intriguing,” Giesser told Healthline, “and if they are shown to translate into efficacy in human trials, [that] would represent significant advances in treating progressive MS.”
Mark Allegretta, PhD, associate vice president of commercial research at the National Multiple Sclerosis Society, did issue a caution.
“This is early laboratory research, so there is no immediate consequence yet for people living with MS,” Allegretta told Healthline.
But, he added, “this kind of systematic approach to screen based on multiple readouts relevant to progressive MS may lead to a compound with greater efficacy.”
“It is always good for people living with MS to communicate with their clinical care professionals,” he advised. “However, clomipramine has not been tested in people with MS, and much more testing is needed to determine if it is safe and efficacious.”