Antidepressant drug clomipramine may help combat the course of multiple sclerosis (MS), suggests a study.

As yet, drugs for this type of MS have been virtually non-existent. In MS patients, leukocytes damage the layer surrounding nerve cells, the so-called myelin sheath. This results in neurological disturbances; in 85 per cent of patients, the disease is characterised by clearly defined relapses and may cause e.g. visual impairment, paralysis or numbness. The majority of patients experience gradual deterioration after 15 to 20 years, which is referred to as progression. In ten per cent of the patients, the disease is progressive from the outset, without any relapses along the way. Researchers collaborating with Prof V. Wee Yong, PhD, from the University of Calgary and Dr Simon Faissner from Ruhr-Universität Bochum screened 1,040 generic therapeutics and, based on preclinical studies, identified one that is suitable for the treatment of multiple sclerosis. 

Today, twelve drugs have been approved for the treatment of relapsing-remitting multiple sclerosis; for the progressive types, on the other hand, only a few therapy approaches exist. "The mechanisms causing damage in progressive MS are not always the same as in relapsing-remitting MS. This is why the latter requires different therapeutic approaches," says Simon Faissner. The team worked with approved drugs, the side effects of which have already been amply documented. From among those drugs, the researchers selected 249 well-tolerated therapeutics that enter the nervous system safely; this is where chronic inflammation occurs in progressive MS. 

Using cell cultures, they tested which of the 249 substances are capable of protecting nerve cells from the damaging influence of iron. In MS patients, iron is released due to cell damage, damaging nerve cells in turn. Following those tests, 35 potential candidates were identified; the researchers subsequently analysed them with regard to additional properties: investigating, for example, if they can reduce damage to mitochondria - the powerhouses of the cells - or if they minimise the activity of leucocytes that attack the insulation of nerve cells in MS patients. In the process, the drug clomipramine proved promising. 

In the next step, the researchers analysed the substance in mice suffering from a disease comparable with relapsing-remitting multiple sclerosis in humans. The therapy suppressed the neurological disturbances completely; as a result, damages to the nerve cells and inflammation were minimised. In a subsequent test, they treated mice with a disease that resembles progressive MS in humans. Here, too, the therapy proved effective, provided the researchers applied it immediately after the first clinical symptoms became apparent. Symptoms such as paralysis were thus reduced - unlike in control animals that were treated with placebo drugs. The findings have been published in the journal Nature Communications.