Old drugs learn new tricks


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The development and approval of new drugs is a difficult and costly task with a high rate of failure. In the majority of the cases failure comes from unexpected side effects that appear while testing is made on human subjects. Drug repurposing is done by using a drug that has already been tested in humans with little to no side effects. Such compounds are then used for a medical condition other than originally intended, limiting therefore unexpected toxicities.

Normally drugs work by targeting specific signaling pathways in the cells. In some cases, the compound never succeeded in their intended application and then are resurrected for a new use in a different disease that can be influenced by the mode of action of the drug. In others, the original intended use is a success, and the repurposing adds an additional indication. Such is the case for the non-steroidal anti-inflammatory drug ibuprofen.

Repurposing of ibuprofen

Studies showed that ibuprofen has the capacity of blocking GTPase RhoA, a key protein that stops neuronal regeneration after damage. Further studies in experimental models led to the conclusion that given at high doses, ibuprofen has indeed a positive effect on functional recovery after spinal cord injury. Different groups using different models confirmed this effect, a fact that greatly justifies the risks and efforts of a clinical trial.

This led to the development of SCISSOR (Spinal Cord Injury Study on small molecule-derived Rho inhibition), a phase I clinical trial designed to test whether the high doses of ibuprofen have any adverse effect of the treated subjects. The study will enroll 12 patients with acute traumatic, motor complete spinal cord injury. They will be enrolled in two groups treated with 2400 mg per day of ibuprofen for 4 (group 1) or 12 weeks (group 2). Each of them will then be carefully monitored for 24 weeks.
SCISSOR is actually the first designed in Germany intervention study aiming pharmacological augmentation rehabilitation after spinal cord injury. The Charité Universitätsmedizin Berlin and the Else Kröner-Fresenius Foundation jointly support it.

What will happen next?

The clinical trial already started recruiting patients and considering the long monitoring time of 24 weeks is expected to be finished by the end of 2017. If no major adverse effect will be recorded in any of the subjects by then this will clear the way to expand the treatment to a larger group of spinal cord injury patients hoping to detect a significant recovery.

Scientists actually hope that ibuprofen might display other beneficial effects such as limiting of neuropathic pain and diminishing of heterotopic ossifications.