- Tropical plants can be a valuable source of new anticancer drugs.
- A formal collaboration with the Sarawak Biodiversity Centre, a Malaysian research organization, has been initiated to study a new experimental agent called silvestrol, which is derived from a rainforest tree growing in Sarawak, Malaysia.
- This agreement will help control costs and expedite further development of silvestrol for potential use in multiple types of cancer.
COLUMBUS, Ohio – The Ohio State University has signed an agreement with the Sarawak Biodiversity Centre in Malaysia to collaborate on the further development and commercialization of a promising anticancer agent derived from a tropical tree that grows on the island of Borneo.
Researchers with Ohio State's College of Pharmacy and Ohio State's Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute have worked together on silvestrol since 2004. The team's early studies indicated that the agent might help treat acute and chronic leukemia, as well as mantle cell lymphoma and other currently incurable malignancies. Silvestrol kills cancer cells in an unusual way, by directly blocking the initial step in the process cells use to make proteins.
Ohio State's new Office of Technology Commercialization and Knowledge Transfer (TCO) brokered the agreement with the Sarawak Biodiversity Centre (SBC), the Malaysian state-run entity responsible for research on biological resources in the state of Sarawak.
Under the agreement with SBC, Ohio State is granted the rights to Sarawak's patent on silvestrol – rights needed to develop and commercialize silvestrol as an anticancer agent. SBC has agreed to carry out the survey and inventory of the resources to provide the raw plant materials to Ohio State in exchange for a share of royalties if silvestrol makes it successfully through clinical trials and is commercialized.
"Representatives from SBC traveled for 36 hours to meet in Columbus this past March," says David Mess, a TCO technology licensing associate. "The meeting at TCO led to an agreement that makes sense for the Ohio State research team, SBC and patients afflicted with cancer."
The SBC was established in 1998 to initiate programs for the research, use, protection and sustainable development of biodiversity in the state of Sarawak.
"The Centre's mission is to discover and harness Sarawak's biodiversity through research and development for the benefit of Sarawak and mankind. The natural product, silvestrol, is one of the most promising candidates that came through" explains Dr. Rita Manurung, SBC's Chief Executive Officer.
During this project, the SBC will oversee the collection and processing of plant material from the Aglaia tree, which grows in Sarawak and from which silvestrol is derived. They are also investigating other leads to maximize silvestrol yields and to identify potential new agents that might be useful for semisynthetic production of silvestrol.
"At Ohio State, we will isolate and purify the agent and conduct the laboratory and animal studies needed to demonstrate its safety and effectiveness," says Dr. Michael Grever, professor and chair of the Department of Internal Medicine, Charles Austin Doan Chair of Medicine and co-leader of the OSUCCC Experimental Therapeutics Program.
"If all goes well, we then hope to begin a clinical trial with silvestrol in three to four years," Grever says.
Dr. David Lucas, a researcher in Grever's laboratory, led recent laboratory studies suggesting that silvestrol might be effective for treating mantle cell lymphoma. The findings were published in the journal Clinical Cancer Research.
"Drug development is a long process, and an agent can be found to be insufficient at any step in that process," says Lucas. "If an agent proves to be too toxic, for example, work on it can come to an end. This agreement takes such contingencies into consideration."
Dr. A. Douglas Kinghorn, professor and Jack Beal Chair of Natural Products Chemistry and Pharmacognosy in the College of Pharmacy, and a researcher with the OSUCCC – James, led the work that fully characterized the molecular structure of silvestrol and also named this compound.
"I have worked in natural-product drug discovery for over 35 years, and the possibility of advancing the new plant-derived agent silvestrol toward the clinic through this agreement as a very positive step," Kinghorn says.
"Not only is silvestrol a very good lead compound for the potential treatment of B-cell malignancies, but if its preclinical development is successful, it may stimulate additional federal grant funding for future natural-products investigators at Ohio State and elsewhere."
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 41 National Cancer Institute (NCI)-designated Comprehensive Cancer Centers and one of only seven centers funded by the NCI to conduct both phase I and phase II clinical trials. The NCI recently rated Ohio State's cancer program as "exceptional," the highest rating given by NCI survey teams. As the cancer program's 210-bed adult patient-care component, The James is a "Top Hospital" as named by the Leapfrog Group and one of the top 25 cancer hospitals in the nation as ranked by U.S.News & World Report.
Journal
Clinical Cancer Research