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About Sickkids
About SickKids

April 11, 2007

Chemicals that regulate neurotransmitter signaling in neurons can also prevent neural stem cell proliferation

Using drugs as probes to interrogate the mechanisms of neural stem cell growth, researchers at The Hospital for Sick Children and Mt. Sinai Hospital have found some surprising facts about how these cells are wired that have important implications for understanding human brain diseases, drug action in the human brain and brain cancer. A number of neuromodulator drugs currently in clinical use for brain disorders have been thought to mainly regulate mature nerve cell circuits in the brain. But chemical screens reveal that these also play a role in regulating the regenerative capabilities of neural stem cells--a potentially important therapeutic target for neurological diseases--and they also show activity against brain tumour stem cells in culture.

This discovery opens the door to the potential of new classes of drugs for the development of brain cancer treatments, and gives new insight into how these compounds may affect normal brain function. Since the drugs are already in clinical use for other diseases, they could be more rapidly deployed or "fast tracked" for use in treating human brain cancer if they show promise in further laboratory studies.

Dr. Peter Dirks, scientist in the Developmental & Stem Cell Biology Program at SickKids, staff neurosurgeon and associate professor of Neurosurgery at University of Toronto, in collaboration with Mike Tyers, investigator in the Samuel Lunenfeld Research Institute at Mt. Sinai Hospital and professor of Medical Genetics and Microbiology at U of T, and Phedias Diamandis, an MD PhD student in the Dirks and Tyers labs, performed a chemical screen on normal neural stem cells using a library of drug compounds currently used in treatment for a variety of diseases, and then applied promising drugs in that screen to brain tumour stem cells in culture. The identification of neural stem cells in the mammalian brain began an era of promise for the treatment of neurological diseases and has yielded new insight into brain cancer. Dr. Dirks' laboratory was the first to report the identification of brain tumour stem cells in 2004, giving a new cellular target for brain cancer treatment.

The study, funded by CIHR, the National Cancer Institute of Canada through the Canadian Cancer Society, the Stem Cell Network, Genome Canada, BrainChild, SickKids Foundation, Jessica's Footprint, and the Baker, Blyth and Kolic families, was published on-line in Nature Chemical Biology's Web site on April 8th.

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The Hospital for Sick Children