Findings provide a new perspective in connective tissue disease research
New research led by Dr. David O'Gorman and PhD student Christina Raykha of the Lawson Health Research Institute has identified a possible new target for treatment of Dupuytren's disease. The Lawson research team is the first to demonstrate that insulin-like growth factor-II (IGF-II) can enhance the ability of cells in Dupuytren's disease to contract tissues. This finding could one day prove beneficial for the thousands of people who suffer from this debilitating disease.
Dupuytren's disease is a heritable condition that causes hand tissues to contract and the fingers to curl permanently onto the palm of the hand. Currently incurable, the "Gold standard" treatment for Dupuytren's disease is surgery, which for many patients can only provide temporary relief. Dupuytren's disease results in a loss of dexterity, making simple tasks like buttoning a shirt and tying shoelaces very difficult.
"Dupuytren's disease is a common and problematic condition for surgeons because the scar-like 'cord' that forms inside the hand often wraps around the adjacent tissues," says Dr. O'Gorman, who co-directs research in the Roth McFarlane Cell and Molecular Biology laboratory, located at St. Joseph's Health Care London, with Dr. Bing Siang Gan. "Your hand is full of small nerves and blood vessels, so removing this contractile cord tissue without damaging these surrounding structures makes this a difficult operation." In addition to the complexity of the surgery and weeks of post-operative rehabilitation, many of these patients will experience a recurrence of finger contractures within 5 years.
The Lawson researchers believe that their findings may profoundly impact understanding of this disease. "IGF-II is an odd and interesting molecule," says Dr. O'Gorman. "Increased levels of IGF-II are found in other connective tissue diseases such as Frozen Shoulder Syndrome, and people with Dupuytren's disease often suffer from this or other connective tissue conditions. IGF-II induces the growth of cancers, and people who have Dupuytren's disease are reported to have a slight, but significantly higher risk of cancer than the general population. Lastly, Dupuytren's disease is much more prevalent in the diabetic population than in the non-diabetic population, and IGF-II levels are increased in type-2 diabetes."
What makes this research important and exciting is that IGF-II has not been previously suspected as a link between these diverse diseases and conditions.
"It's a bit of a paradigm shift for the field because no one was looking at this molecule as a potential target," says Dr. O'Gorman. "However, in retrospect, there is a lot of complimentary information about IGF-II that now makes a lot of sense."
Using patient samples obtained through the Roth McFarlane Hand and Upper Limb Centre at St. Joseph's Hospital, Dr. O'Gorman's research team is uniquely positioned to research Dupuytren's disease. Using cells grown from the tissues removed during surgery, they can answer questions such as how does IGF-II induce these cells to contract tissues in the hand? What happens when you block IGF-II or deplete it in the hand tissues of these patients? Why is Dupuytren's disease so common in some families and not in others?
"At the end of the day we would like to come up with a therapeutic intervention that could block the signaling pathways activated by IGF-II in hopes that it might be useful as an adjunct to surgery. By doing this we might delay or even stop the recurrence of this disease...that would make a huge difference in the lives of these patients."
The finding was recently published in the scientific journal Biochimica et Biophysica Acta-Molecular Basis of Disease.