Another pathway to remyelination-Anti-inflammatories

Preisner A et al. Non-steroidal anti-inflammatory drug indometacin enhances endogenous remyelination.Acta Neuropathol. 2015 May 6. [Epub ahead of print]

Multiple sclerosis is the most frequent demyelinating disease in the CNS that is characterized by inflammatory demyelinating lesions and axonal loss, the morphological correlate of permanent clinical disability. Remyelination does occur, but is limited especially in chronic disease stages. Despite effective immunomodulatory therapies that reduce the number of relapses the progressive disease phase cannot be prevented. Therefore, promotion of neuroprotective and repair mechanisms, such as remyelination, represents an attractive additional treatment strategy. A number of pathways have been identified that may contribute to impaired remyelination in MS lesions, among them the Wnt/β-catenin pathway. Here, we demonstrate that indometacin, a non-steroidal anti-inflammatory drug (NSAID) that has been also shown to modulate the Wnt/β-catenin pathway in colorectal cancer cells promotes differentiation of primary human and murine oligodendrocytes, myelination of cerebellar slice cultures andremyelination in cuprizone-induced demyelination. Our in vitro experiments using GSK3β inhibitors, luciferase reporter assays and oligodendrocytes expressing a mutant, dominant stable β-catenin indicate that the mechanism of action of indometacin depends on GSK3β activity and β-catenin phosphorylation. Indometacin might represent a promising treatment option to enhance endogenous remyelination in MS patients.

Indometacin (INN and BAN) or indomethacin (AAN, USAN and former BAN) is a non-steroidal anti-inflammatory drug (NSAID) commonly used as a prescription medication to reduce fever, pain, stiffness, and swelling. It works by inhibiting the production of prostaglandins, molecules known to cause these symptoms.Since indomethacin inhibits both COX-1 and COX-2, it inhibits the production of prostaglandins in the stomach and intestines, which maintain the mucous liningof the gastrointestinal tract. Indomethacin, therefore, like other non-selective COX inhibitors can cause peptic ulcers. These ulcers can result in serious bleeding and/or perforation requiring hospitalization of the patient. To reduce the possibility of peptic ulcers, indomethacin should be prescribed at the lowest dosage needed to achieve a therapeutic effect. So the question here is what is the dose and dose it work.

I have been posting these types of post because you want to hear about remyelination treatments and I think you can see over the past few years there have been more and more and more and more of these types of claims about finding remyelination switches. Therefore, it is becoming a bit like “EAE cure of the week” and so accept my apologises if my comments become more and more bland. Because we need to see evidence that the approaches can work before our enthusiasm levels go up.

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