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Two McGill scientists are leading an international research team that announced a breakthrough last week: they have isolated a section of a human chromosome that makes people vulnerable to leprosy.
Medicine and human genetics professor Erwin Schurr and human genetics professor Tom Hudson were two of the co-authors of a research paper announcing the discovery in the March issue of the journal Nature Genetics. The announcement has already stirred considerable interest, for a problem that Canadians may think is relegated to the past.
"That depends on where you live," said Schurr, a genetics researcher at the McGill University Health Centre. "On a global scale, there are 500,000 to 700,000 new cases each year. These cases are not equally distributed around the world; there are a few high incidence countries that account for the vast majority of cases."
Schurr led a team that went to some of those countries to collect DNA samples from members of affected families. The most afflicted countries are India and Brazil; some African, Asian and South American nations also have new cases every year.
The disease is very rare in Europe and North America and most of the developed world, and the number of cases in afflicted countries has gone down thanks to aggressive multi-drug chemotherapy. Symptoms of leprosy include skin lesions, permanent nerve damage leading to numbness of the feet and hands and, if left untreated, the disease may result in gross disfiguration including loss of finger, toes, feet and hands. The leprosy bacteria are transmitted through direct personal contact.
"Before the introduction of drug therapies 20 years ago, there were about 3 million new cases a year. So the caseload came down, but the question is why hasn't it gone away completely? We believe our discovery is an answer to that."
While the team has not yet identified the actual gene, they have narrowed down its location to a specific area on human chromosome 6.
"The gene predisposes people to becoming infected; it provides a friendly environment for the bacterium (Mycobacterium leprae, the known cause of the disease)."
Tom Hudson, director of the McGill University and Genome Quebec Innovation Centre, says that the gene is almost certainly a mutant version of a healthy gene carried by all humans. He says the significance of the breakthrough can be placed in the context of long-term and ongoing efforts to show a genetic component to infection.
"People at the McGill Centre for Host Resistance — Schurr, (Philippe) Gros, (Emil) Skamene and others — have been working for two decades to show that we get infectious disease not just because of bugs, but also because of genes that make us susceptible. The group has shown in the past that genes played this role in animals, but this is one of the first times that the genetic link has been shown in humans."
The research team for this study used state-of-the-art gene mapping techniques to look for a common thread between affected families.
"We started off not knowing where the gene is, so it was necessary to test all chromosomes. We were looking for inheritance patterns that correlated with infection by the disease. We noticed that brothers and sisters who both have leprosy often inherited the same pieces of chromosome 6. On average, siblings share 50 percent of genes, but here the correlation was much higher than that. So that's how we know we're close to the gene."
The next step will be to identify the culprit and analyze it.
"We will identify the gene, and the molecular nature of the defect, in a year at most," Schurr predicts. "Once that is done, the most likely treatment to come down the road will be the development of new vaccines; the current vaccine in use is not very effective. If we understand where exactly the body's defence breaks down, we can develop a vaccine intervention targeted against this deficiency."
Schurr explained that the immune system of affected individuals may not be able to identify the pathogen when it invades the cells, and a more effective vaccine would help it zero in on that weak point.
"We know we can correct this vulnerability because nature has already corrected it in many people. It's a good approach, because we will be learning from nature itself."
Schurr and Hudson are collaborating with researchers at the Hôpital Necker in Paris and the Dermato-Venereology Hospital in Ho Chi Minh City, Vietnam. They also worked with graduate students, including Hudson's PhD student (and the paper's co-author) Marcelo Mira, who is from Brazil, a country heavily afflicted by leprosy. The study is funded in Canada by the Canadian Institutes of Health Research (CIHR), the Canadian Genetic Diseases Network and Genome Quebec.