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Repurposing an Anti-Inflammatory Drug to Treat a Life-Threatening Disease

– Contributed content –

Schistosome worm

Schistosome worm (Natural History Museum, London)

Susana Fares Mazloum

3 June 2019. Researchers successfully identified a common drug compound, a non-steroidal anti-inflammatory, that is active against all growing stages of the parasite that causes schistosomiasis.

Already available in the pharmaceutical market, the non-steroidal anti-inflammatory (NSAID) mefenamic acid, has shown potential to treat a life-threatening neglected disease. Although not widely known, schistosomiasis is one of the most devastating human parasitic disease after malaria, with approximately 600 million people currently affected, causing approximately 300,000 deaths per year, a number expected to increase.

Schistosomiasis is caused by the schistosoma worm, a waterborne parasite. The only treatment for this neglected disease so far is a single drug, praziquantel, widely administered to populations where the disease is most prevalent. However, this situation with only one treatment often leads to drug resistance, which is now the case for many people at risk of contracting this disease.

A team of Brazilian researchers, led by professors Josué De Moraes and Eloi Lago from The Neglected Disease Center at University of Guarulhos, has successfully tested mefenamic acid on lab animals induced with schistosomiasis, which reveals an active against all growing stages of the parasite.

The team set a goal to find a new treatment for this disease through drug repurposing. This strategy is becoming more attractive due to the high costs, long lead times, and risks of developing new drugs. The latest estimates (2016) from the Tufts Center for the Study of Drug Development, puts the cost of taking a new drug through clinical trials to pharmacy shelves at about $2.7 billion. The total cost may range from $10 million to $2 billion, depending on the purpose of the new drug.

Moreover, a major factor in the high cost of new drugs are human clinical trials. But 90% of medicines that go through the human trials process will not reach the market, because their results will show the drugs to be unsafe or ineffective. Therefore, drug repurposing, particularly with neglected diseases, makes sense.

In this study, published on 23 April in the open-access journal eBioMedicine, 73 NSAIDs already on the market, were initially evaluated for their anti-schistosomal properties using phenotypic screening strategy. Those which demonstrated effectiveness against the parasite were further tested in lab animals induced with the disease.

The most effective NSAID was mefenamic acid, which seems to reduce more worm burden, egg production, and enlarged liver and spleen conditions related to the disease. These results were further confirmed by scanning electron microscopy analysis.

The exact mechanism by which mefenamic acid is able to exert its effect on the parasite is still unknown to the researchers, yet the apparent damage to the parasite suggests that the inherent lipophilicity — ability of a compound to dissolve in fats, oils, lipids, and non-polar solvents — may aid in the drug absorption and help the drug to reach its molecular targets.

Mefenamic acid is widely used for short-term treatment of mild to moderate pain from various conditions, including pain and blood loss from menstrual periods. Although, it may not replace praziquantel, it may be used in conjunction to better treat schistosomiasis.

Susana Fares Mazloum is currently involved in cancer research, specifically melanoma, at the Federal University of São Paulo in Brazil. She’s also a co-author in this research.

Updated: 4 June 2019

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