Toronto Western Research Institute

Arthritis: Predicting Probability of Joint Replacement Surgery
The need for improved patient education of people with arthritis is highlighted in new work by UHN researcher Dr. Elizabeth Badley, Dr. Gillian Hawker (Women's College Hospital) and other Toronto-based researchers who looked at factors underlying a patient's decision to undergo joint replacement surgery.

In a prospective study, the researchers recorded information about 3,307 seniors who were experiencing symptoms of arthritis in 1995-1997. In 1999, the researchers followed up with 2,103 respondents and found that—out of factors including education level, height, weight, socioeconomic factors, employment and living arrangements—the most important determining factor was willingness to have the surgery.

"Joint replacement surgery is a cost-effective treatment for debilitating arthritis of the hip and knee, and disparities in rates of surgery are troubling. Willingness to consider surgery as a treatment option results from improved patient understanding. This underlines the fact that we need to continue to develop and implement strategies to educate the community about arthritis and replacement surgery outcomes," says Dr. Badley.

Arthritis Rheum. 2006 Oct;54(10):3212-20. [ Abstract ]

Brain Injury: Research at the Forefront of New Therapies
A new UHN finding is the first step towards developing new multi-pronged strategies for traumatic brain injury (TBI).

Damage to a brain cell sets off a cascade of internal and external events that combine to create a toxic environment, killing neighbouring cells over a large area. While neuroscientists are starting to understand this complex mechanism, treatments which address a single component of the cascade have proven unsuccessful in clinical trials. Thus researchers are moving to a multi-pronged paradigm to address two or more components simultaneously.

A pioneering study led by Dr. Michael Tymianski and graduate student Anthony Lau has shown that due to the effects of a lethal by-product of cell damage called peroxynitrate, TBI therapy should include both anti-oxidant and anti-apoptotic compounds.

"If we can use molecular approaches to prevent the oxidizing process, which forms hazardous reactive oxygen molecules in the brain, and the apoptosis process, which leads to programmed cell death, we may be able to reduce cell death in these injuries," explains Dr. Tymianski.

J Neurosci. 2006 Nov 8;26(45):11540-53. [ Abstract ]

Degenerative Disc Disease: Notochord Cells Help to Regenerate Disc Cartilage
Drs. Mark Erwin and Robert Inman have discovered that notochord cells-which are primitive organizing cells of the developing embryo-release a factor called connective tissue growth factor (CTGF) that may be responsible for providing certain strains of dogs with their remarkable resistance to degenerative disc disease.

Degenerative disc disease is one of today's most common and costly medical conditions, marked by a progressive loss of disc height, mechanical properties and tissue degradation. However, in resistant dog strains it does not occur or occurs much later in life.

To find out why resistant dogs are protected, the UHN team obtained notochord cells from the discs of the dogs and determined the identity of some of the proteins secreted by these cells. They then used the proteins secreted by these cells to determine what disc cell genes are turned on by these notochord cells.

"Our results suggest that certain breeds of dogs are protected against this disease because their discs contain an abundance of notochord cells that are releasing CTGF," says Dr. Inman. "This research will likely provide the groundwork to regenerate disc cartilage for patient treatment in the future."

Arthritis Rheum. 2006 Dec;54(12):3859-67. [ Abstract ]

Spinal Cord Injury: Rebuilding from the Ground Up
A team led by TWRI researcher Dr. Michael Fehlings has demonstrated a new way to reconstruct an essential element in nerve function in the spinal cord in a paper jointly co-first authored by Drs. Eftekhar Eftekharpour and Soheila Karimi.

A tissue called myelin functions as an insulating casing around nerve fibers and takes part in conducting signals from the brain to the rest of the body. After transplanting specific neural precursor cells (aNPCs) from the brain of adult transgenic mice into the spinal cords of mice which lack myelin, investigators were able to generate oligodendrocytes—the building blocks of myelin—which traveled down the spinal cord and formed mature myelin.

"This is a major step forward in spinal cord injury research," says Dr. Fehlings. "The ability to restore the myelin insulation is a key component of a therapeutic strategy, and our study is the first to show this exciting result. Our future work will focus on generating neural precursor cells from alternative sources including embryonic stem cells and in applying this technology is concert with tissue engineering approaches to repair chronic spinal cord injury."

J Neurosci. Mar 28, 27(13): 3416-28. [ Abstract ]