MS therapy enters new grounds after surprising discovery.
Multiple Sclerosis (MS) is a disease characterized by lesions in the nervous system induced by the loss of the protective sheaths that cover nerve fibers and assure the proper transmission of electric impulses. This is caused in part by an autoimmune reaction, in which immune cells attack and progressively damage the protein myelin that is the main constituent of the protective neuronal coating. Current therapies are based on immunosuppressive drugs that can restrain this detrimental activity of immune cells . But these drugs also have harmful effects.
Another known characteristic of MS patients is that certain cells – called oligodendrocytes – that should deposit new myelin, and thus repair the lesions, are unable to do so, being blocked in an undifferentiated (non mature) state. This leaves us, and researchers, with an important question: Could oligodendrocytes be reactivated and induced to produce myelin in MS patients, thus possibly curing the disease?
In a study published in Nature, scientists from the Scripps Research Institute screened a collection of about 100’000 drugs to find molecules that can promote oligodendrocyte differentiation and stimulate myelination. Among the molecules that were able to induce myelin production in oligodendrocytes in vitro, they suprisingly identified benztropine. This is a well-known drug already used in the treatment of Parkinson’s disease, but its effects on oligodendrocyte differentiation had never been described.
The researchers went on to test if benztropine is also effective in vivo and administered it to mice suffering from MS-like lesions. They observed that benztropine could significantly decrease the severity of the disease by promoting the formation of new myelin sheaths and the recovery of the lesions. Moreover, when benztropine was combined with immunosuppressive drugs commonly used in MS treatment their effects were additive.
This study is an important advancement in the research for MS treatment. It demonstrates that drugs that promote oligodendrocytes differentiation, that have never been tested before, may effectively induce the repair of the myelin sheaths and prevent their destruction at least in an animal model.
Unfortunately, benztropine can have neurological and psychic side effects at certain doses, so the goal now is to identify other molecules that are able to induce myelin deposition but lack benztropine’s undesirable properties. It’s also essential to confirm the effects of benztropine, or of similar compounds, on human cells and in MS patients.
The combination of molecules promoting remyelination with immunosuppressors is a new, promising therapeutic strategy for MS. The two types of drugs have different mechanisms of action and they can cooperate in promoting the recovery of the lesions. Moreover, therapeutic effects can be achieved with lower doses of drugs when they are administered together, and hence their side effects can be remarkably reduced.
Photo: Flickr, kharied
Source: Deshmukh VA, Tardif V, Lyssiotis CA, Green CC, Kerman B, Kim HJ, Padmanabhan K, Swoboda JG, Ahmad I, Kondo T, Gage FH, Theofilopoulos AN, Lawson BR, Schultz PG, & Lairson LL (2013). A regenerative approach to the treatment of multiple sclerosis. Nature PMID: 24107995
multiple sclerosis, parkinson, immune, cells, molecules, therapy, benztropine, lesions, drugs, medicine, myelin