SMARD - spinal muscular atrophy with respiratory distress
The term “orphan disease” is commonly applied to any debilitating medical condition that affects fewer than 200,000 Americans, young or old. These are rare diseases, but, regrettably, at last count, there were at least 6,000 of them, including SMARD—spinal muscular atrophy with respiratory distress.
SMARD is a life-threatening motor neuron disorder. Symptoms of SMARD are commonly seen within the first six months of life. Because SMARD undermines voluntary muscle function, infants who inherited a defective gene from both parents may be unable to lift their heads or may have other mobility limitations. Their inability to breathe or cough makes them susceptible to pneumonia and other respiratory infections. Children with the disorder stop breathing due to a paralyzed diaphragm and often die in their sleep. As a result, many children with SMARD never see their first birthdays.
Thanks to research taking place at The Jackson Laboratory, there is hope for the future for those affected by this disorder.
Professor Greg Cox, Ph.D., and his research team within The Jackson Laboratory in Bar Harbor, Maine, is one of the few genetic scientists committed to better understanding SMARD—spinal muscular atrophy with respiratory distress. This rare motor neuron degenerative disorder is a devastating scourge for the children and families who are coping with it.
“As genetic diseases go, SMARD is the rarest of the rare,” Dr. Cox says. “It’s a very early onset and very rapidly progressing motor neuron disease. One of the nerves affected is the phrenic nerve, which impacts the diaphragm. When the diaphragm is paralyzed, you lose the ability to breathe and, survival requires a ventilator.”
Jackson Laboratory research utilizes a laboratory mouse model of SMARD, which emerged as a spontaneous mutation within the massive vivarium maintained in Bar Harbor to study an extensive array of human diseases. It’s the only mouse model of the rare disease, and it’s a key tool used by the few researchers worldwide who are exploring potential therapies that would modify or neutralize the defective gene that underlies SMARD.
“This mouse very closely models the progressive loss of motor neurons seen in the human disease,” Dr. Cox says. “There is one area where the mice seem to differ; the phrenic nerve is less severely affected. While the mouse model doesn’t exactly match the pattern we see in human patients, it’s the best tool we now have.”
Dr. Cox is eager to advance his SMARD research by studying motor neurons from mouse stem cells to determine if the disorder can be reproduced in a system that can be directly observed. He also wants to expand this work to use cells derived from human skin tissue, which would allow human forms of SMARD to be cultivated in a laboratory setting, offering the opportunity to test the efficacy of various genetic modification strategies. That work will require additional funding.
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