Over one million Canadians suffer from a rare disease. In Dr. Bill Gibson’s lab at BC Children’s Hospital, scientists are studying rare mutations and their effects on the human body. Their efforts are helping doctors care for children with rare diseases and revealing the origins of more common health conditions.
In a study recently published in Diabetes by Dr. Gibson and UBC PhD student Chi Kin Wong, one patient’s rare mutation has led to the discovery of two proteins that help prevent diabetes from developing. Wong talks about how this research could lead to new treatments for diabetes and what rare diseases can teach us about how the human body works.
You recently published research in Diabetes that began with a mutation in a single patient. Tell us about what happened.
In addition to pursuing scientific research, my supervisor, Dr. Bill Gibson sees patients as a geneticist. In his clinical role, he diagnosed a young adult patient with a mutation in the gene that codes for a protein called p300. This patient had developed a rare form of diabetes despite having none of the usual risk factors like obesity or inactivity. We wondered if her mutation might have contributed to her diabetes, so we decided to study the p300 protein and its role in the body.
What did you discover?
Diabetes occurs when the body either can’t produce insulin or can’t properly use the insulin it creates. Without insulin, the body can’t process sugars for energy. This leads to high levels of sugar in the blood, which can damage organs, blood vessels and nerves.
We suspected that p300 might play some role in body’s ability to create and use insulin so we studied mice with the p300 mutation and mice with a mutation in the gene that codes for a protein called CBP, which is similar to p300. In both kinds of mice, we found defects in cells in the pancreas that produce insulin and glucagon, another hormone that helps the body maintain a steady blood sugar level. These mice developed glucose intolerance, a condition in which the body has trouble processing sugars that is known to lead to the development of diabetes.
This research shows us that p300 and CBP help prevent diabetes from developing by ensuring the pancreas has enough insulin-producing cells. There’s more work to do, but this is our first step towards fully understanding the role these proteins play in diabetes in humans. One day, we may be able to develop treatments that target these proteins to prevent or treat diabetes.
Does this research improve care for patients with the p300 mutation?
Yes, this research suggests that people with a p300 mutation may be at a high risk of developing diabetes at a young age. During our work, we came across several BC Children’s Hospital patients with different p300 mutations who have not yet developed diabetes. Now that doctors know these children may be at risk for diabetes, they can monitor them more closely.
If there is one thing about this research you’d like to share with the general public what would it be?
Rare diseases are relevant to all of us, not just to people who are directly affected by one. When we study rare diseases, we not only learn about these conditions and how to help affected patients, we also gain important insights about more common illnesses.
Many common diseases, including obesity, diabetes and cardiovascular disease that are usually caused by a complex combination of genetic and environmental factors also have “rare versions,” that are caused by one specific genetic mutation. By studying these rare versions, we can understand how these diseases develop and the role certain genes play in the human body.
In this case, finding a patient with a rare version of diabetes and a mutation in the gene that codes for p300, suggested to us this protein plays an important role in the hormone-secreting part of the pancreas. Studying p300 is helping us understand how insulin producing cells work, and may eventually lead to insights that help us prevent, treat or cure diabetes.
This research is supported by the Canucks for Kids Childhood Diabetes Laboratory at BC Children’s Hospital, BC Children’s Hospital Foundation, National Sciences and Engineering Research Council of Canada, and the Canadian Institutes of Health Research.