Canadian Gene Cure Foundation
Foundation Canadienne Géne Cure 

Dr. Alex MacKenzie of Children's Hospital of Eastern Ontario Research Institute showed us in 2009 what was possible with a grant of just $25,000 by assessing a different use of a drug that is already available.

Dr. MacKenzie shares with us a bit about his project: Spinal Muscular Atrophy or SMA is a disorder which involves the nerve cells which carry impulses from the brain and spinal cord to our muscular system. This type of nerve cell known as the motor neuron dies off in SMA leaving infants and children weaker and in the most severe cases unable to breathe. SMA is one of the most common inherited causes of infant death with an incidence of 1 in 10,000 live births. Although a gene is usually deleted in SMA, there is a second almost identical gene present in all children with SMA. This gene makes lower levels of the protein which when missing causes SMA; the ability to turn up this second gene to make more of the missing protein has become a goal of our lab and a number of others.

We have identified drugs in use in the clinic today which we have shown turn up this rescue gene in nerve cell culture. We would now like to test the drugs in mice, both normal and mice with SMA, to establish whether what we have observed in the Petri dish holds true in living organisms. We shall establish whether the protein levels are indeed increased in motor neurons as well as monitoring for a reduction in the disease severity seen in the mouse that have been genetically engineered to develop SMA. What is observed in mice frequently is also seen in humans as well; thus if the effect is recapitulated it would suggest that we should move directly to human clinical trials. The advantage of assessing drugs which are in clinical use is that we shall be able take this step rapidly.

Dr. William Foulkes who specializes in cancer genetics as a physician and researcher was awarded $70,000 for his research titled, "Correcting the splicing in the mismatch repair gene PMS2 as a model for therapy of genetic diseases". Dr. Foulkes explains:
"We are particularly keen to see this project progress because the disease in question, early-onset cancer, affects a very under-served Canadian population, that is, the Inuit of Nunavik, Quebec. This region of Quebec is huge, but has a very small population (less than 12,000) and has poorly developed infrastructure and multiple health needs. We have now identified several different unrelated families who carry the same alteration in a cancer-related gene. In this project, we will explore possible mechanisms of correcting splicing of the gene PMS2, which when mutated, is a cause of early onset cancers, particularly of the brain, blood system and gastrointestinal tract. We will try to use molecules called morpholinos to interrupt the function of the new mutation, which creates a de novo splice site. If this is successful, we should see more normal protein being produced by the cells, instead of the non-functioning protein produced by the mutation. The normal protein acts a kind of "genome protector", so that if we can restore protein levels to something near normal, we may see, at least in the laboratory, evidence for correction of the cancer phenotype."

He also tells us that the funding he received will greatly impact the work because it will "allow it to continue!" and that "it is very difficult to get work funded for diseases that affect just a few people".

Dr. Robinson and his team were awarded $75,000 to do testing on a series of compounds to identify possible drug treatment for mitochondrial diseases. Approximately one child every week is born with a genetic abnormality, which seriously decreases the ability of their cells to produce energy. Their organs are not able to function normally, and without treatment these children suffer progressive nerve and organ failure. In this present grant, Dr. Robinson's approach should lead to new uses for existing FDA approved drugs and also add new naturally occurring compounds to the potential list for mitochondrial disease therapy.

Dr. Goodyer and his team were awarded $75,000 to investigate possible new treatments for cystinosis. This rare genetic condition is ten times more prevalent in Quebec, where it is responsible for nearly one third of childhood kidney transplants. These children lack the ability to recycle the amino acid cystine, which then accumulates to toxic levels causing progressive tissue damage. Patients can be treated with cysteamine, but results are far from optimal. Dr. Goodyer says, "Our research program offers a multi-faceted approach to the development of new therapeutic strategies for this rare but devastating disease."

Dr. Rosenblatt and his team were awarded $65,000 to explore the use of different forms of vitamin B12 to treat a rare disorder of vitamin B12 metabolism. In 2006, Dr. Rosenblatt's team discovered a new gene (MMACHC) responsible for the most common genetic cause of vitamin B12 deficiency. Mutations to this gene prevent the body from converting vitamin B12 into its active forms. A lack of this essential nutrient leads to a variety of symptoms, from severe anemia to birth defects and developmental delay in childhood. Dr. Rosenblatt's laboratory is one of only two in the world that is providing clinical diagnosis as well as research in this area.

Dr Jacques Galipeau and his team at McGill University were awarded a $65,000 grant to study genetic enhancement of stem cells. This will enable them to develop a new treatment for patients affected by the neuronopathic forms of Gaucher disease. Gaucher disease is a lysosomal storage disorder caused by a deficiency of the enzyme glucocerebrosidase. Patients typically suffer an enlargement of the liver and spleen, low blood platelets and anemia. In some patients - as many as 300 Canadians - the disease also affects the brain, resulting in a debilitating loss of motor skills. The brain dysfunction, which can prove to be fatal, is currently untreatable because enzyme supplements cannot cross the blood-brain barrier.

University of Montreal researcher, Dr. Daniel Bichet was awarded a $65,000 grant for his studies into Nephrogenic Diabetes Insipidus (NDI). One of the few rare and inherited human genetic disorders, NDI can be fatal. This disease affects the kidney, leaving young children to suffer from chronic dehydration. If undiagnosed, the severe bouts of dehydration can also lead to mental retardation. Dr. Bichet's human genetics research currently targets the V2 receptor and its role in causing the disease and offers free testing for families affected by this disease.

Research Update: The grant he received was extremely helpful and permitted testing of a novel rescue compound which, however, brought negative but new interesting knowledge related to the maturation and endocytosis of mutant vasopressin receptors. There is considerable interest for the treatment of Nephrogenic Diabetes Insipidus with pharmacological chaperones and Dr. Daniel Bichet's research is continuing to contribute to the general knowledge, early detection and treatment of this rare genetic disease.

McGill University endocrinologist, Dr. Constantin Polychronakos was awarded $65, 000 for his research of Type 1 juvenile diabetes. His initial research confirmed that children, whose disease is the result of a rare genetic mutation, can be treated with oral medication rather than painful injections. Oral medication allows children to produce their own insulin, which assures near-perfect control of their blood sugar. Control of blood sugar for those suffering from Juvenile Diabetes can never be achieved with insulin injections.

Research Update: Dr. Constantine Polychronakos says, "We are optimistic that molecular medicine is ushering in the era of personalized medicine. Genetic profiling will allow us to distinguish, from among individuals with the same diagnostic label, the ones that are likely to benefit from a given treatment. Even the most successful treatments have responders and non-responders; in many cases, response will be able to be predicted from genetic profiling in the not too-distant future."

Dr. Michael Hayden and Dr. Bruce Carleton of the University of British Columbia were granted $65,000 to continue their research into adverse drug reactions in children. The ultimate objective of this study is to provide safe and effective drug therapy for children suffering from human genetics disorders. Hayden and Carleton will work in conjunction with many other children's hospitals and health centers across Canada to further their genetics research.

Dr. Eyal Grunebaum was awarded $40,000 for his human genetics research into gene therapy strategies in Purine Nucleoside Phosphorylase Deficiency (PNP). PNP causes increased frequency of severe life threatening infections as well as hematological and neurological abnormalities in children. Most of the children affected with this disease will die in their first decade of life. There is no treatment currently available, thus Dr. Grunebaum's goal is to develop an effective gene therapy approach that may ultimately offer a remedy for children with PNP deficiency, with a secondary goal of shedding light on the treatment of other human genetic disorders.

Dr. Cheryl Wellington was granted $40,000 for her research into Down syndrome, a very common genetic disorder caused by inheritance of an extra copy of chromosome 21. Individuals with Down Syndrome have several ongoing health problems, including: diabetes, obesity, gallstones and eventually, early-onset Alzheimer's Disease. The focus of Dr. Wellington's project is the gene ABCG1, which is a cholesterol transporter that is found on chromosome 21. This research will determine whether treatment can be made available to those suffering from health problems associated with Down Syndrome by influencing ABCG1 function.