Identification of drugs that can be repurposed to prevent neurodegeneration

2012  -  Toronto, ON, CA

Organizations

The Hospital for Sick Children

Project description

Neurodegenerative disorders represent one of the largest unmet medical needs. One of the characteristics of these disorders is the degeneration or death of axons, the portion of nerves that transmit information. As a consequence, the processes by which cells communicate in the brain are altered, resulting in significant functional, cognitive and mental impairments and, in many cases, death. There have been few approaches to discover agents and therapies that specifically block axon degeneration. We have identified two drugs approved to treat cancer that are unusually effective at preventing degeneration, and that have not previously been thought of as potential treatments for nervous system-related diseases.

Relevance to the acceleration of therapeutics in neurodegenerative diseases of aging

In this project, we will investigate whether these cancer drugs are effective on many nerve populations, and if they prevent degeneration in Parkinson’s and Alzheimer’s disease rodent models.

Anticipated outcome

If the cancer drugs prove to be neuroprotective and effective in treating neurodegeneration, we will have identified two drugs already available to patients that can be rapidly “repurposed” to use for neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease.


Final abstract

Neurodegenerative disorders represent one of the largest unmet medical needs. One of the characteristics of these disorders is the degeneration or death of axons, the portion of nerves that transmit information. As a consequence, the processes by which cells communicate in the brain are altered, resulting in significant functional, cognitive and mental impairments and, in many cases, death. There have been few approaches to discover agents and therapies that specifically block axon degeneration. We identified two drugs approved to treat cancer that are unusually effective at preventing degeneration, and that have not previously been thought of as potential treatments for nervous system-related diseases. Both drugs suppressed the degeneration of a number of different kinds of nerve cells grown in a dish, including dopamine, cortical, or sympathetic neurons that degenerate in Parkinson’s disease. One of the drugs also protected dopamine axons from degeneration in a rodent Parkinson’s disease model. We have thus identified drugs that can be readily and rapidly “repurposed” to use for neurodegenerative disorders.

This project was a collaboration between the laboratories of Drs. David Kaplan (team leader) and Freda Miller at the hospital for Sick Children, and Dr. Jonathan Brotchie at the Toronto Western Research Institute. During the one and half years of this research, the team expanded to include Dr. Louis-Eric Trudeau (University of Montreal), Dr. Larry Kromer (Georgetown University, U.S.A.), Dr. Doug Zochodne (University of Alberta), and Dr. Lee Rubin (Harvard University).