Parasitic worm genomes reveal novel treatment possibilities

Parasitic worm genomes reveal novel treatment possibilities

5 Nov 2018 - 16:00

About the study

  • A new genomic study of parasitic worms has identified almost a million new genes 
  • Analysis of the parasitic worm genomes predicts many new potential drug targets
  • These drug targets could potentially be used to discover new drugs to prevent and treat the diseases caused by parasitic worms worldwide

5 November, Hinxton – The largest ever genomic study of parasitic worms has identified hundreds of thousands of new genes and predicted many new potential drug targets which could be used to discover new drugs for the prevention and treatment of diseases caused by parasitic worms.

The research, published in Nature Genetics, was carried out by the Wellcome Sanger Institute, EMBL’s European Bioinformatics Institute (EMBL-EBI), Washington University in St. Louis, Edinburgh Genomics and other collaborators. It will help scientists understand how parasitic worms infect humans, evade the immune system and cause disease.

Parasitic worms cause many neglected tropical diseases (NTDs) – conditions which receive relatively little funding for research and treatment. NTDs caused by parasitic worms include river blindness, schistosomiasis and hookworm disease, and blight the lives of over a billion people globally. Infections can last many years or even decades, leading to severe pain, major physical disabilities, delayed development in children, and social stigma associated with deformities. There has been little investment in parasitic worm research, despite the huge health burden that parasitic worm diseases inflict – often on the poorest countries of the world.

To understand how worms can infest and live inside people, the researchers compared the genomes of 81 species of roundworms and flatworms, including 45 that had never been sequenced previously. Their analysis revealed almost a million new genes that had not been seen before.

Data vs disease

Anti-worm treatments have remained unchanged for years and are often inadequate. In addition, an over-reliance on just a few existing drugs may lead to the development of drug resistance in worms. To search for new interventions, the researchers mined the dataset of 800,000 worm gene sequences to predict drug targets and identify compounds that could be used to develop anti-worm drugs. Making use of ChEMBL (EMBL-EBI’s database of bioactive molecules with drug-like properties), they narrowed the list down to 40 high-priority drug targets in worms, and hundreds of possible existing drugs that could act upon them.

“We compared the data from the sequencing work with the extensive drug discovery data in the ChEMBL database,” explains Andrew Leach, Head of Chemistry Services at EMBL-EBI. “We used this to identify potential compounds, based on their known bioactivity profiles, which are more likely to be relevant for one of the presumed protein targets in these parasitic worms. This information can then be used to help us develop new drugs, or utilise existing ones, to treat diseases caused by parasitic worms.”

Repurposing drugs

Further research could lead to a raft of new treatment possibilities to help improve the lives of the millions of people suffering from diseases caused by these worms.

“The spectrum of drugs available to treat worm infections is still very limited,” adds Avril Coghlan, a senior bioinformatician at the Wellcome Sanger Institute. “We focused our search by looking at existing drugs for human illnesses. This may provide a fast-track route to pinpointing existing drugs that could be repurposed for deworming.”   

Source article

Avril Coghlan et al. (2018) Comparative genomics of the major parasitic worms, Nature Genetics DOI 10.1038/s41588-018-0262-1

Image credit: Dave Goulding, Wellcome Sanger Institute, Genome Research Limited

Funding
This work was supported by Wellcome, UK Medical Research Council, US National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases, National Institute of General Medical Sciences, and other funders. Please see the paper for full list of funders.

Contact the news team

Oana Stroe
Communications Officer
stroe@ebi.ac.uk
+44 (0)1223 494 369

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