 This is the remarkable story of the discovery of a putative, topical drug for the treatment of psoriasis and for a pipeline of other drug candidates to treat a range of human ailments from cancer and neutropenia to rheumatoid arthritis and inflammatory bowel disease.
It all began in a research laboratory at Simon Fraser University where my graduate students were exploring different aspects of management of crop diseases caused by soil-dwelling nematodes and insects.
There was a particular focus on improving the success of biological control of a beetle pest of strawberries and rhododendrons by using insect pathogenic nematodes. These naturally occurring, microscopic nematode worms wriggle through the soil around the roots of plants searching for insect larvae which they parasitize and kill. Interestingly, as so often happens in the biological world, these little nematode worms don't operate alone, and in this case it is in combination with symbiotic bacteria that the nematode causes the insects' demise. The nematodes inoculate the insect with specific bacteria and, working together, they kill the insect. To effectively control the insect pests of crops large numbers of these nematodes are applied to the soil and, subsequently, the insect cadavers release large numbers of the bacteria into the soil.
My question to one of the new graduate students, Genhui Chen, was what is it that these symbiotic bacteria produce and do these bacterial substances influence the population of the naturally occurring soil fungi and bacteria? For the next several years Mr. Chen researched these questions and he was very successful. Of course, the project grew as he raised more questions whilst answering others. Additional personnel were brought in (eg. Dr. Jianxiong Li, an organic chemist) as the project evolved and the results, we judged, had very significant potential.
Around the world other research groups were also exploring different aspects of this three way nematode-bacterial-insect interaction; some kinds of antifungal substances produced by these bacteria were already known. However, the research direction on these bacterial secretions that was taken by our team was different and, subsequently, led to the creation of Welichem Technologies Ltd in 1985 that morphed, in 2000, into Welichem Biotech Inc. By this time Genhui Chen had obtained his doctorate, the research having left the University was evolving rapidly, enabling the company to become an established biotech company focused on the research and development of pharmaceutical drugs.
Through the development of its searching, chemical synthesis and screening process, Symbiochem TM, Welichem has discovered an array of compounds, many of them novel chemical structures, which have potential as chemotherapeutic drugs against inflammatory/autoimmune diseases, cancer and infectious diseases. Welichem is focused on taking its lead drug candidate (WBI-1001) for the topical treatment of psoriasis to clinical trial this summer, subject to regulatory approval. This will be followed by a novel cancer drug candidate that is currently in preclinical trials. Other compounds with putative chemotherapeutic benefit are in the pipeline ready for future testing.
Welichem is thus an exciting place with an exciting story and exciting future!
As we all reflect upon our surrounding world, on the beauties of nature and on the challenges we have in maintaining this natural grandeur while trying to manage the medical challenges of a growing human population, we tend to forget what is underground, out of sight, in the soil. We need to appreciate those treasures too, even the little worms, as they too are part of nature's beauty and balanced contribution to our planet.
The key to what we were observing in our experiments was that the nematode-bacterium complex was secreting substances into the insects' blood that overcome the insects' innate immune defence system and so enabling the bacteria and nematodes to survive and multiply rapidly. The bacteria also secrete antifungal and antibacterial substances which minimized decay of the insect cadaver, thus enabling the bacteria and nematodes to continue feeding and reproducing with minimal competition.
Dr. John M. Webster
February 2007
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