📋 Tender Overview
Ancestry.com wont help you find your common relative with a mouse humans evolutionary path diverged from that of mice about 65 million years ago. But that doesnt mean we dont share family traits with the little mammals including all of our physiological systems and most of our genes.So mice can develop the same diseases as humans for the same genetic reasons. Because they breed prolifically and are small and easy to maintain in laboratory conditions mice were the natural choice for study by the first mammalian geneticists in the early 20th century. And today mice are the premier model for the entire spectrum of biomedical research from basic investigations into the role of individual genes to the design of targeted therapies for human diseases.You can find that full spectrum in a lab in Bar Harbor Maine. Rob Burgess a professor at The Jackson Laboratory JAX is now developing a gene therapy for a rare variant of an inherited form neurodegenerative condition called Charcot-Marie-Tooth CMT disease based on discoveries he made in mice some 15 years ago.CMT is actually a collection of inherited diseases of the peripheral nervous system Burgess says. These hereditary neuropathies are neurological disorders that cause damage to the peripheral nerves the bundles of nerve cell fibers that connect the brain and spinal cord to muscles and sensory organs. The neuropathies in the CMT category involve more than 100 different genetic mutations with varying impact on the severity of symptoms which include sensory deficits and muscle atrophy.In 2006 in a paper in the journal Neuron Burgess published his labs discovery of a mouse model with the mutation in the gene known as GARS for glycyl-tRNA synthetase corresponding to the mutation in patients with the category of CMT known as CMT2D. GARS like other tRNA synthetase genes is essential for protein production in every cell of the body. So it might be expected that a mutation in GARS causing CMT2D in mice would involve failure of protein production. Instead Burgess demonstrated that the mutation had a destructive role specifically targeted to peripheral neurons.Collectively the diseases known as CMT may be the worlds most common inherited neuromuscular disorder with an estimated incidence of one case per 3000 people. But many of the subtypes represent tiny populationsCMT2D for example is rarer than one in 250000. Burgess lab works to understand the genetic mechanisms involved in CMT2D with the long-term goal of finding ways to prevent and treat all CMT patients.That work exclusively involved mouse models until the day eight years ago when Burgess opened an email from Houston pediatric neurosurgeon Stephen Fletcher M.D.A cure for CarolineFletchers granddaughter Caroline was a doe-eyed two-year-old who was not keeping up with the first steps of her twin brother Henry. A genetic test revealed that Caroline had been born with the CMT2D mutation.Burgess work in CMT2D put him at the top of Fletchers search results. Burgess responded to Fletchers initial email inquiry with sympathy expressing regret that he couldnt offer any immediate help and recommending that Fletcher reach out to clinical researchers who work with patients not mice.Soon Fletcher would connect with Scott Q. Harper Ph.D. a gene therapy researcher at Nationwide Childrens Hospital in Columbus Ohio. It took some time but ultimately Harper would team up with Burgess in the hunt for a genetic therapy for CMT including the version Caroline carries.By 2019 Burgess and Harper would coauthor a paper in the Journal of Clinical Investigation in which they demonstrated an effective gene therapy in a mouse model engineered to carry Carolines mutation. As promising as this proof of concept is there are currently huge regulatory and financial hurdles to overcome before the treatment can be administered to Caroline. Together with Fletcher the researchers are reaching out to foundations set up to expedite gene therapies.When Burgess talks about Caroline now nine his face clouds with concern. Shes a really bright kid and she reads well above grade level but shes confined to a wheelchair he says quietly. We want to help her now to see if we can stop her disease from progressing.Principal investigators are often pulled in many different directions and sometimes arent able to provide 100 percent focus to all things. Not Rob. One of his special qualities is presence.Fletcher says It was evident after my search for help on a rare problem that Burgess was the go-to person. His track record of excellence in the field was clearly the right choice for our family. As important and maybe even more of a factor was his compassion for our family and his passion for what he was doing to help us. We are eternally thankful for Dr. Burgess and the Jackson Lab team. Any and every discussion about Carolines story he says always includes the Burgess-JAX factor.It has been an absolute pleasure to collaborate with Rob says Harper who is a principal investigator in the Center for Gene Therapy at Nationwide Chldrens Abigail Wexner Research Institute in Columbus Ohio as well as professor of pediatrics at The Ohio State University College of Medicine. Seems like hes always the smartest person in the room and yet disarming and humble. Principal investigators are often pulled in many different directions and sometimes arent able to provide 100 percent focus to all things. Not Rob. One of his special qualities is presence.
