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Open-Source Discovery Seeks Neglected Disease Drug

Mycetoma regions

Regions where mycetoma occurs (Drugs for Neglected Diseases initiative)

7 February 2018. An international online collaboration is using an open process to discover new drug compounds to treat mycetoma, a slow-progressing inflammatory fungal disease occurring mainly in developing regions, which up to now is largely neglected. The initial draft manuscript of a paper outlining the project was posted on 2 February in the journal bioRxiv for comment by interested researchers worldwide.

The Mycetoma Open Source project is led and the paper authored by researchers from University of Sydney in Australia, Erasmus Medical Center in Rotterdam, the Netherlands, Drugs for Neglected Diseases initiative, or DNDi, in Geneva, Switzerland, and Medicines for Malaria Venture, also in Geneva. Mycetoma, also known as eumycetoma, results from a fungus entering the body through the outer skin layers, usually the feet among people walking barefoot. The disease progresses slowly but often results in an inflamed mass under the skin, which can spread to the bones, causing deformities, loss of function, and even death.

Mycetoma is found in tropical and sub-tropical regions, with cases reported in Chad, Ethiopia, India, Mauritania, Mexico, Venezuela, Senegal, Somalia, Sudan, and Yemen. World Health Organization says the disease is so neglected that accurate data on its incidence and prevalence are not available. There are no known dedicated diagnostics, and the only treatments available are antibiotics. In some cases, says WHO, the disease is caught so late in its progression, amputation is often the only treatment.

In the paper, the team led by Sydney chemistry professor Matthew Todd and Erasmus microbiologist Wendy van de Sande are seeking collaborators to contribute to the discovery of compounds to treat mycetoma. The paper reports on an initial screening of 800 molecules, resulting in first in 215, then 35 candidates. Among the most active compounds is an analog of fenarimol, an anti-fungal agent known to act against against rusts, blackspot, and mildew fungi. DNDi reviewed fenarimol as a treatment for Chagas disease, a parasite-born disease.

The researchers so far narrowed down the fenarimol analogs to 4 candidates, with tests in lab cultures and with larvae models, and is asking for collaborators to continue the drug discovery process. The team plans to communicate online with Twitter and Reddit, and share files over GitHub.

The Mycetoma Open Source, or MycetOS. project hopes to follow the same successful path as an earlier  similar open-source malaria drug-discovery initiative. In a DNDi statement, van de Sande points out that the initial research team does not “own” the work done so far, and needs full-scale colleagues to carry it forward. “This early work merely starts a process of discovering potential new chemical entities for eumycetoma,” says van de Sande, “and we invite anyone interested to identify how they might contribute and participate as an equal partner in this search for a new treatment for this most neglected of tropical diseases.”

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