UVic research offers new promise for future treatments of genetic diseases
- Mina Tawadrous
Dr. Francis Choy and his team at the UVic’s Centre for Biomedical Research are investigating three rare, inherited diseases that affect young children and for which there are, as yet, no affordable and reliable treatments. All three diseases—Gaucher disease, Sanfilippo syndrome and glycine encephalopathy—involve the inability to produce certain enzymes necessary for intracellular structures called lysosomes and mitochondria to digest and eliminate used material.
People with Gaucher disease, a lethal condition, lack an enzyme responsible for breaking down a particular fat and preventing its accumulation in such essential organs as the spleen, liver, bones and brain. Although rare, Gaucher disease is the most common form of lysosomal storage disorder, affecting an estimated 1 in 50,000 peop#8804; however, the frequency is far greater in Eastern European Jews, estimated to be 1 in 850 people.
A promising project currently under way in Choy’s lab relies on the expression of a human synthetic (recombinant) enzyme fused to a special protein that can act as a vehicle to transport the enzyme through the blood-brain barrier. Ultimately, this method may lead to new opportunities for therapeutic treatment of Gaucher disease within the brain.
Choy’s research lab is using a similar method in its work on Sanfilippo syndrome. People with this condition lack an enzyme needed for the breakdown and disposal of certain sugar chains. Few affected children survive beyond their teens. There is no effective treatment. Choy’s research aims at producing the missing enzyme and delivering it to the target organ—the brain.
The third inherited disorder, glycine encephalopathy, is a lethal disease caused by the body’s inability to break down glycine, an amino acid that builds muscle and converts sugars into energy. It is generally diagnosed during late infancy and shows itself in jerky seizures and delays in development, progressing to difficulty in breathing, requiring artificial respiration. Those who do not die during the first year of life develop profound intellectual disability and seizures that are difficult to treat.
Choy is using synthetic DNA technology to produce a protein component of this enzyme complex and deliver it to vital organs of the body. One of his graduate students, Agnes Zay, earned the Lieutenant Governor’s Silver Medal for her master’s thesis on this disease (see http://ring.uvic.ca/07jun07/zay.html). Zay synthesized the protein, enabling researchers to produce it in large quantities—a first and critical step towards developing an inexpensive diagnostic test for the disorder. The results of Zay’s trials are expected to aid in the diagnosis of glycine encephalopathy during future prenatal screening.
A former PhD student of Choy, Dr. Graham Sinclair, is supervising the development of a program for screening every newborn in BC for 22 genetic diseases plus eight secondary conditions. As a biochemical geneticist and clinical laboratory scientist for the Newborn Screening Lab at BC Children’s Hospital, Sinclair has overseen the expansion of the program from three to 30 screened disorders as of 2011.
Choy frequently serves as a consultant to the BC government and various medical centres across Canada in order to predict which patients affected by genetic diseases might benefit from an enzyme supplement treatment.
“It is an exciting time to study these storage diseases, particularly as a result of recent advancements in stem cell research and gene studies,” says Choy. He adds that this work helps researchers understand the disease mechanisms in addition to possibly shedding light on related disorders. And the study and comparison of various symptoms may lead to potential drug targets for use in treatment.
“I am not only here as a scientist but also to motivate and inspire students,” says Choy. “Supervising graduate and post-doctorate students and teaching undergraduate students —watching them experience the acquisition and creation of knowledge, and build their confidence—that is my best reward.”