Spinal cord injury is physically and emotionally devastating. It robs people of their ability to move and forces them to adopt a completely different lifestyle.
Currently, an estimated 36,000 people live with spinal cord injuries in Canada. The causes of injury vary from car accidents to medical conditions to sports-related accidents.
For those who suffer from spinal cord injuries, the costs of home care can vary from $1.25 million to $25 million over the course of their lifetime. There are fears that these costs will only increase.
Dr. Joseph Culotti, a Senior Investigator at the Samuel Lunenfeld Research Institute at Mount Sinai Hospital, part of the University of Toronto's Health Research Network, is using research to try and eliminate the physical and emotional costs of spinal cord injury. He's hoping that, by better understanding spinal cord development, new methods for spinal cord repair will be possible.
Unlike other health researchers who use mice and rats for experiments to study the nature of spinal cord injuries, Dr. Culotti studies worms, known formally as nematode C. elegans.
"C. elegans is one of the simplest animals to which we can apply the powerful tool of genetics," says Dr. Culotti, "and understand how the nervous system develops."
Even though worms possess only 302 neurons (nerve cells) compared to billions for humans, his team is credited with discovering startling similarities between how nematode neurons grow and move and how this process operates in the developing human spinal cord.
The key to unraveling this process involves better understanding what's taking place at the molecular level: which genes are active, what signals are being sent, how these signals are received and what is the result of these communications. In other words, what gets turned on or off and how this affects the development of the spinal cord.
The process starts with a molecule called UNC-6 or netrin, also referred to as a 'guidance cue', which holds information about where and how neurons are meant to form cellular extensions. The extensions, called axons, are long fibers (which can stretch up to one meter in length in humans) that carry electrical nerve impulses from one neuron to another. Before these axons can form, information from UNC-6 must be relayed to developing neurons. This job is carried out by two other molecules, UNC-5 and UNC-40, called receptors which are programmed to respond to signals from UNC-6.
Dr. Culotti and other groups have discovered that similar molecules exist in the developing human spinal cord. In human beings, for instance, the axons can stretch up to one meter in length. But once a person reaches adulthood, the 'guidance cue' molecules are no longer as effective because other molecules prevent new neuron growth and work to maintain the status quo.
When a person sustains an injury to their spinal cord, neuron connections are severed, and these same molecules prevent any chance for regrowth through signals. A novel therapy would be to figure out how to encourage the neurons to reject these signals and reconnect. This would, in effect, convince the body that the spinal cord is still in a state of development.
In order to allow for these kinds of new therapies, Dr. Culotti has focused on the details of how UNC-6, UNC-5 and UNC-40 signal to one another. In other words, how do these molecules know how to send and receive signals from one another? And what are the exact steps that occur during this process?
This work led to the recent discovery of a protein called UNC-129. UNC-129 provides novel insights into how molecules like UNC-6, UNC-5 and UNC-40 are regulated in fine detail. Regulation of a molecule involves defining its structure and function. Any absence of regulation can lead to defects that are important to the development and potential regeneration of the nervous system. If UNC-129 exists in humans, Dr. Culotti may be able to find further clues to spinal cord repair.
"Dr. Culotti's efforts are world-class," says Dr. Rémi Quirion, Scientific Director of CIHR's Institute of Neurosciences, Mental Health and Addiction (INMHA). "Results from his work have already led to novel hypotheses regarding the treatment of persons suffering from spinal cord injuries. I'm optimistic that some of these new treatment strategies will be applied in clinics sometime in the near future."
The Barbara Turnbull Award in Spinal Cord Research
In March 2006, Dr. Culotti was named the 2005 recipient of the Barbara Turnbull Award for Spinal Cord Research.
In 1983, at the age of 18, Barbara Turnbull was the victim of a shooting at a Toronto convenience store. The gunshot severed her spinal cord and left her paralyzed from the neck down. After the incident, Ms. Turnbull graduated with a degree in journalism from Arizona State University (class valedictorian) and secured a job as a reporter at the Toronto Star. On top of her duties as a reporter, Ms. Turnbull lectures in various cities about the benefits of spinal cord research, and directs a foundation established in her name.
The $50,000 annual prize established in her name in 2001 represents a partnership of The Barbara Turnbull Foundation (BTF), NeuroScience Canada (NSC), and CIHR's Institute of Neurosciences, Mental Health and Addiction (CIHR-INMHA). It supports an outstanding CIHR-funded researcher who contributes to the advancement of world-leading spinal cord research conducted in Canada.
Dr. Culotti was pleased to have been selected as the 2005 recipient.
"Barbara is a tremendously well balanced individual and a true inspiration," says Dr. Culotti. "I am pleased to accept the award on behalf of my laboratory. We all feel tremendously honoured by it."
Ms. Turnbull feels that the award recognizes Dr. Culotti's significant research achievements which are motivational for other health researchers.
"This is important scientific work," she says. "It provides inspiration and encouragement to all those following this increasingly promising path toward spinal cord remediation and, ultimately, a cure."
"NeuroScience Canada is proud to be a partner on the Barbara Turnbull Award for Spinal Cord Research. Recipients have focused on the basic level of cell repair, to rehabilitation and developing devices to improve the lives of patients," said Inez Jabalpurwala, President of NeuroScience Canada. "We congratulate Dr. Culotti for his excellent work, and thank Barbara Turnbull for her untiring efforts to raise awareness about the devastating impact of spinal cord injuries, and the need to accelerate the pace of neuroscience research."
As for future prospects of a cure, Dr. Culotti considers scientific collaboration to be the essential ingredient that will lead to success in spinal cord repair.
"What our lab does is only the beginning," he says. "We provide some pieces to the puzzle, but not all of them. Getting all the pieces and putting them together is an effort requiring the entire scientific community."
Next Month in the June Research Profile - Every day, the average adult breathes about 15,000 to 20,000 litres of air. But there are toxic pollutants in this air, such as sulphur oxides and ammonia, that people just don't even consider. Given that June 7 is Clean Air Day, the next research profile will look into one CIHR-funded researcher's environmental research efforts that look at the negative implications of air pollution on human health.
