Putting the Ice Bucket Challenge Funds to work
The ALS Society of Canada announced the team led by Dr. Lawrence Korngut, MD at the University of Calgary received the first Arthur J. Hudson Translational Team Grant. The team also includes Dr. Lorne Zinman, MD from Sunnybrook Health Sciences Centre and University of Toronto. Together, they will pursue “A randomized controlled trial of pimozide in subjects with ALS”; a Phase II study involving 100 participants across 8 ALS clinics across Canada.
This trial, led by the Principal Investigator of the Canadian Neuromuscular Disease Registry (CNDR) and the Chair of the Canadian ALS Research Network (CALS) will examine whether pimozide will examine whether pimozide, a drug already approved by Health Canada for schizophrenia and Tourette’s syndrome, might slow progression of ALS. Pimozide can stabilize neuromuscular function, which means it can strengthen the connection between the motor neuron and the muscle (called the neuromuscular junction or NMJ). It is hoped that by strengthening this connection, there will be preservation of transmission of signals from the brain to the muscle and slowing of paralysis in ALS.
This Hudson Grant will also fund the validation of an exciting new potential biomarker. Biomarkers are ways of monitoring the body (eg. looking for something in blood or doing a particular physical examination) to either diagnose ALS earlier, select individuals for a trial or monitor effectiveness of a treatment. In recent years, ALS researchers have placed great emphasis on clinical trial biomarkers that ensure the drug is doing the action it is intended to in humans. Without knowing this, it is impossible to determine if an experimental ALS treatment worked or didn’t work as a result of affecting the body function scientists think it was targeting.
In ALS clinics, neurologists utilize a procedure to stimulate an individual’s motor neurons and examine their ability to trigger muscle function. For decades, neurologists have observed that repetitive stimulation of motor neurons can lead to decreased response of muscles in many people with ALS (called decremental response) and it is hypothesized that this may be a result of poor NMJ connectivity and transmission as motor neurons degenerate. Since pimozide strengthens or restores the NMJ, Dr. Korngut’s team will measure whether this decremental response can be a biomarker to recruit individuals likely to benefit from pimozide, but also to monitor whether pimozide is acting as hypothesized so a positive or negative result on ALS can be properly interpreted. This means if pimozide does slow ALS progression, we will know whether or not it is a result of NMJ connectivity.
“What is most exciting about this portion of the project is that Dr. Korngut will examine the effectiveness of this biomarker in a small pimozide human trial that is already underway at the University of Calgary,” said Dr. David Taylor, Director of Research for ALS Canada. “Should it work, the biomarker can also be used to recruit individuals with the highest likelihood to respond to pimozide treatment for the Hudson Grant funded, 100 participant clinical trial across the country.”
The CNDR, led by Dr. Korngut, is an innovative platform for organizing patient information to facilitate clinical research and is routinely recognized as one of the best organized ALS registries in the world. In this trial, the CNDR will allow for more efficient recruitment of participants, better data management and improved monitoring of participants following the trial. Furthermore, CALS, led by Dr. Zinman, is the incorporated network of 15 academic ALS multidisciplinary clinics across Canada. Working together the CNDR and CALS are utilizing optimal infrastructure to initiate and execute clinical trials in a manner that is unique to Canada.
Testing pimozide in the clinic is the next step in a series of projects that have taken several years to develop. Pimozide was first discovered as a potential treatment for ALS in the Canadian labs of Drs. Pierre Drapeau, Alex Parker and Richard Robitaille at Université de Montréal working with zebrafish, worm and mouse genetic models. These individuals are pioneers of the translational team concept in Canada and ALS Canada/Brain Canada are fortunate to have the opportunity to support the first large clinical study produced by this visionary pipeline. We look forward to watching the progress of this study with great excitement. ALS Canada is committed to increasing the opportunity for Canadians living with ALS to participate in clinical trials of exciting new experimental therapeutics. The first Arthur J. Hudson Translational Team Grant will provide this opportunity and lay further groundwork for future clinical trials in Canada.
The Arthur J. Hudson Translational Team Grant was first announced on May 3, 2014 at the ALS Canada Research Forum. This new grant program funds teams of Canadian researchers to accelerate the movement of ideas out of the laboratory and into the clinic with the hope of assisting development of new therapeutics for ALS. It is the cornerstone of our ALS Canada Research Program designed to emphasize bench-to-bedside translation. For the first time ever, ALS Canada, in partnership with Brain Canada, have utilized an International Peer Review Panel consisting of seven European and American ALS experts, spanning the basic to clinical spectrum, who convened in Toronto in November to determine the top project amongst strong competition.