Research Achievements

Research

A new test to help doctors monitor and treat type 1 diabetes

Researchers have developed a new blood test that could help doctors monitor patients with type 1 diabetes, potentially leading to improved predictions about disease progression and more effective, personalized treatments. UBC has filed a provisional patent in the U.S. for the test panel, which measures regulatory T cells (Tregs), a type of immune cell that doesn’t work properly in people with type 1 diabetes. The researchers identified a genetic signature that allows them to distinguish Tregs from the many other types of cells present in blood. This gene pattern can be used to measure changes in Tregs using just a small sample of a patient’s blood. This discovery has the potential both to help scientists study type 1 diabetes and improve clinical care of the condition. Dr. Megan Levings led the study, published April 2016 in the science journal Diabetes.

Genetic variation increases risk of high blood pressure and blood sugar levels in children on some antipsychotic medications

Researchers at BC Children’s Hospital and the University of British Columbia have reported an underlying biological factor that predisposes children to complications associated with second-generation anti-psychotic medication use. Their study found that children with a genetic variation called C677T on the MTHFR gene were six-times more likely to have metabolic syndrome when treated with second-generation anti-psychotic medications. These drugs are prescribed to children and youth in British Columbia for treatment of psychotic disorders, mood and anxiety disorders, attention deficit hyperactivity disorder, autism spectrum disorders, adjustment disorders and substance abuse. The researchers say it’s concerning because the medications prescribed to treatment a chronic disease – mental illness – and then the children develop risk factors for a second chronic disease. Dr. Dina Panagiotopoulos and Dr. Angela Devlin were the study co-authors on this work, which was published January 2012 in Translational Psychiatry.

New national guidelines for children on anti-psychotic medications

Youth taking certain types of anti-psychotic medications have three times the risk of developing abnormally high blood sugars (pre-diabetes) or Type 2 diabetes and two times the risk of becoming overweight or obese, according to study results published November 2009 in the Canadian Journal of Psychiatry. Approximately 5500 youth in B.C. use these medications and prescription rates are rising. The study’s principal investigator, Dr. Dina Panagiotopoulos and Dr. Jana Davidson of BC Children’s Hospital and the University of British Columbia, emphasize to patients and their caregivers that, despite these findings, patients should continue to take these medications as prescribed by their physicians. Dr. Panagiotopoulos and Dr. Davidson have also contributed to national recommendations for clinicians on monitoring and managing the care of children who take these medications. These recommendations were published in the Journal of the Canadian Academy of Child and Adolescent Psychiatry in August 2011.

Immune discovery may lead to new treatments for type 1 diabetes

Proteins called chemokines help keep our bodies’ defenses in check by preventing the immune system from mistakenly harming healthy tissue, new research has found. This discovery may lead to new therapies that stop the unwanted immune attacks that cause disorders like type 1 diabetes and multiple sclerosis or life-threatening organ rejection in transplant patients. The discovery will help researchers learn more about which immune pathways need to be ‘fixed’ to slow, stop or prevent the harmful immune responses that lead to autoimmune disorders.

Treg immune cells usually prevent the immune attacks that cause type 1 diabetes, multiple sclerosis and other autoimmune conditions. In this study, scientists found that Tregs make chemokine proteins that attract potentially harmful immune cells. Once the immune cells come into close proximity with the Tregs, the Tregs send chemical signals that stop them from attacking healthy tissue. This is the first study to reveal chemokines also help prevent the immune system from harming healthy tissue.

In comparing blood samples from children with type 1 diabetes to samples from healthy children, the scientists found that Tregs in diabetic children produced fewer chemokines, suggesting that problems with Treg function play a role in the development of diabetes.

This finding could help researchers develop new therapies that prevent or treat autoimmune disorders and tissue rejection by ensuring Tregs are making enough chemokines to work correctly. The research was led by Dr. Megan Levings and published February 2016 in The Journal of Clinical Investigation.

Preventing diabetes in mice

Children develop type 1 diabetes when their own immune system attacks the cells in the pancreas that produce insulin. A team of researchers led by Dr. Bruce Verchere at BC Children’s Hospital and the University of British Columbia have found a way to block this immune attack and prevent type 1 diabetes in mice. The researchers increased a protein called CCL22 in the mice’s insulin‐producing beta cells. This protein attracted other protective cells that blocked the immune attack and prevented diabetes. This discovery could lead to a drug that prevents the progression of type 1 diabetes in people newly diagnosed with the disease. It could also lead to new drugs for overcoming organ rejection in transplant patients. The team reported their findings August 2011 in the Journal of Clinical Investigation.

Gene discovered for Weaver syndrome

Scientists have found a gene that causes Weaver syndrome, a rare genetic disorder that typically causes large size at birth, tall stature, developmental delay during childhood and intellectual disability. Published December 2011 in the American Journal of Human Genetics, the discovery led to the development of a DNA diagnostic test that is now available internationally. Testing the EZH2 gene for mutations could help families who are seeking a diagnosis for their child.

The study was led by Dr. William Gibson at BC Children’s Hospital and BC Women’s Hospital & Health Centre. Dr. Gibson organized the first International Conference on Weaver Syndrome in 2014, bringing together families affected by the disorder and related overgrowth conditions along with the doctors, scientists and students who specialize in these rare disorders.

Cholesterol levels in beta cells play key role in diabetes

Scientists at BC Children’s Hospital and the University of British Columbia have discovered that high levels of cholesterol in the pancreatic beta cells damage the body’s ability to secrete insulin and this may contribute to the development of type 2 diabetes. The scientists found that a gene called ABCA1 is key to regulating cholesterol levels in the pancreatic beta cells, which produce and secrete insulin and are impaired in type 2 diabetes. The gene transports cholesterol out of the cell and it also plays a key role in making HDL cholesterol – the good kind – in the blood. When ABCA1 is defective, as shown in a mouse model, the body is unable to regulate cholesterol in the beta cells and therefore cannot properly secrete insulin. The researchers say these are the first data directly implicating cholesterol levels in the pancreatic beta cell as having a role in insulin secretion. The findings point to ABCA1 in the beta cell as a new target for treating diabetes, and show that cholesterol has to be very tightly regulated.

Dr. Michael Hayden and Dr. Bruce Verchere, scientists at BC Children’s Hospital and the University of British Columbia, co-led the study, which was published February 2007 in Nature Medicine.

Scientists engineer immune cells to protect transplants from rejection

Scientists have developed a gene therapy that programs Treg immune cells to protect transplanted tissues from rejection by the patient’s immune system. After transplantation, the recipient’s body sometimes identifies the transplanted tissue as foreign and mounts an immune attack against it. For this reason, most transplant patients must take immune-suppressing medications for the rest of their lives.

This finding opens up the possibility to build a gene for any disease where the immune system is overactive. This includes autoimmune diseases, which develop when the immune system destroys healthy tissues such as beta cells, the insulin-producing cells of the pancreas in Type 1 diabetes. A decade of further work is needed to develop safe and targeted treatments using modified Tregs to prevent immune attack of transplants. Led by Dr. Megan Levings, the research was published March 2016 in The Journal of Clinical Investigation.