Genetic work carried out at Memorial University in Newfoundland has contributed to the identification of the gene mutation responsible for a rare condition known as congenital indifference to pain (CIP). Patients with this condition are normal in every way except that they do not feel pain, although they can feel sensations like touch and temperature. With further research this discovery may lead to the development of pain medications which can be used by the general population with fewer side effects than drugs currently available.
Results from work done by Xenon Pharmaceuticals Inc. to identify the gene mutations responsible for CIP, were recently reported in the Globe and Mail and will soon be published online in Clinical Genetics. CIP is an extremely rare condition, with fewer than 30 reported cases in the world literature, and the Xenon study has the largest collection of families reported to date. The study included nine families from seven different countries, including one multi-generation Newfoundland family with four affected individuals. The Xenon paper in Clinical Genetics describes the CIP families and the discovery of the gene mutations. Researchers from the U.K. reported on the relationship of the SCN9A gene to CIP in a paper in the December 2006 edition of Nature, based on three CIP families from Northern Pakistan.
David King, president and CEO of the Genesis Group, the technology commercialization arm of Memorial University, said the discovery of this gene mutation is an excellent example of how families from Newfoundland and Labrador have contributed to recent developments in genetic research. “Memorial has been collaborating in a number of Canadian and international studies addressing rare diseases related to pain and heart disease as well as more common diseases.”
Mr. King said, “Newfoundland and Labrador is an excellent location to conduct genetic research because of its unique founder population descended of a small group of Irish and English immigrants from the late 1700s and because we have, unlike most jurisdictions, ready access to long-term census data. In this province we also have a medical research community and healthcare system that can gather excellent clinical data.”
In the CIP gene mutation discovery, genetic researchers in Memorial’s Faculty of Medicine identified and diagnosed the subjects with CIP, carefully documented the medical condition and then traced back their family trees. The expansion of the study to identify CIP families in other parts of the world was important in the verification of the Newfoundland findings and to confirm the applicability to other populations. This genetic information then opened the door for other researchers to determine the mechanism of the disorder at a molecular level.
Mr. King pointed out that “the province’s emerging biotechnology sector, together with recent research initiatives at Memorial, are allowing us to progress further along the discovery pathway from genetics to the molecular levels of genomics and proteomics and then to clinical trials.” He noted that there are already two Newfoundland companies investigating a variety of diseases. Newfound Genomics has the capacity for large-scale gene sequencing and is investigating type II diabetes, inflammatory bowel disease and osteoarthritis. NewLab is involved in clinical research on conditions associated with psoriasis.
At Memorial, Dr. Terry-Lynn Young, in partnership with Genome Atlantic and Dalhousie University, has established a facility to conduct genomic research on inherited diseases and Dr. Valerie Booth, in partnership with NewLab, has created a proteomics facility, which can work on ways to identify and control proteins produced from target genes. Memorial and the local companies are currently pursuing a public/private partnership initiative to create a major integrated facility to accelerate the growth of this promising new biotechnology sector.
The willingness of family members is what allows this type of genetic research to take place. Memorial University bioethicist Dr. Daryl Pullman said that one of the important ethical considerations in genetic research is the concept of “benefit sharing.” The International Human Genome Organization recognizes that the human genome is part of the common heritage of humanity and that genetic research should foster health for all human beings. In genetic research on some diseases such as diabetes or cancer, the benefit to families participating in the study is very direct and significant. Potentially, diagnostics, therapeutics or even vaccines may result from the research, which may control or even cure the disease for the participating subjects and all their descendants. In the case of rare diseases the research participants are providing a tremendous, unselfish donation to society in total while a much smaller benefit may accrue to them directly. In the studies in which Memorial is participating the university ensures that the extended families of participants will receive genetic counselling and will be given the option of molecular testing to determine who is a carrier of the genetic change. This allows families to better plan their future and, in the case of CIP, allows parents to find out if an infant has the disease so that protective measures can be taken to control the child’s environment to prevent injuries that might otherwise occur due to their lack of pain sensation.
An example of where research on a rare genetic disease in Newfoundland and Labrador has proved of benefit to the families involved is ARVC (arrhythmogenic right ventricular cardiomyopathy). ARVC is a disease which results in the sudden and unanticipated death of a person usually well before middle age. Genetic researchers have pinned down the location of the gene responsible for ARVC. While there is presently no cure, those at risk can have a small cardio-defibrillator implanted in their chest, which can restart the heart if it stops. This procedure has already saved the lives of a number of ARVC patients in this province.
Mr. King said that moving from gene discovery to the development and approval of new treatments is a lengthy and expensive process, which requires a huge investment from the private sector. “However, if information learned from these recent exciting genetic discoveries contribute to the development of new drugs, a portion of the profit generated will be returned to the province to underwrite the public health care system which supports the people who suffer from these diseases and to provide research funding to search for treatments for other diseases that have such a profound impact on society.”
Dr. Pullman noted that these are the sort of issues that can be addressed by the new Provincial Health Research Ethics Board, about to come into existence to oversee all human research in the province.