Previously existing drugs for multiple sclerosis (MS) can mainly relieve the initial relapsing disease. In many patients, however, the disease later turns into progressive MS, in which the disability of those affected increases gradually. This form can not be treated adequately at present. Possible reasons for the lack of effective treatment for progressive MS have been summarized by an international team of researchers in a review article in Nature Reviews Drug Discovery of 9 August 2019.
The Bochum physician Prof. dr. Simon Faissner and Prof. Dr. med. Ralf Gold from the Department of Neurology at the St. Josef Hospital, Klinikum der Ruhr-Universität Bochum, cooperated with Prof. Dr. med. V. Wee Yong from the University of Calgary and Prof. Dr. med. Jason Plemel from the University of Alberta in Edmonton. In the article, they discuss the mechanisms underlying progressive MS and discuss laboratory and clinical data on potential therapeutic approaches. The authors combine the discussion of therapy goals with the results of pharmacological studies from cell culture and animal models as well as ongoing clinical studies.
A disease, many mechanisms
“A bottom line of our analysis is that it is so difficult to treat progressive MS because the progression of the disease is driven by various mechanisms,” says Simon Faissner. “To make the treatment more efficient, we will probably need more precise therapeutic approaches that target multiple disease mechanisms simultaneously.” Another problem, according to the authors, is that so far there is not a sufficiently good animal model that maps the abundance of underlying mechanisms , “Therefore, it is challenging to identify drug candidates for a clinical trial,” said Faissner.
In addition, previous clinical trials have often followed different endpoints, so therapeutic success was defined differently from study to study. Uniform criteria, according to the authors, would be desirable to make work comparable and to demonstrate reliable treatment effects.
But there are also financial aspects that are an obstacle to the development of drugs. Although there are indications that drugs that are approved for another indication could also act against multiple sclerosis. “However, as patent protection for these funds has already expired, pharmaceutical companies can not develop them further,” explains Simon Faissner. “Therefore, conducting studies on the effectiveness of these agents in MS often fails because there is no funding for it.”
Better therapy possible
Nonetheless, the authors conclude that progressive MS could be better treated in the future because researchers are increasingly understanding the underlying disease mechanisms. “With these findings, a more targeted therapy will be possible, which prevents those affected in the course of the disease are increasingly exposed to adverse effects,” predicts Faissner.