Will Ward’s birthday falls on Rare Disease Day (Feb. 28). That’s an interesting coincidence because he has a rare disease: X-linked myotubular myopathy (MTM), a rare, muscle-weakening disease that affects only boys. Originally on Snapchat, this video captures the Ward family’s recent visit to the lab of Alan Beggs, PhD to learn more about MTM research.
Beggs, director of the Manton Center for Orphan Disease Research at Boston Children’s Hospital, has known Will since he was a newborn in intensive care. In this lab walk-though you’ll see a freezer filled with muscle samples, stored in liquid nitrogen; muscle tissue under a microscope; gene sequencing to identify mutations causing MTM and other congenital myopathies and a testing station to measure muscle function in samples taken from animal models.
Beggs’s work, which began more than 20 years ago, led to pivotal studies in male Labrador retrievers who happen to have the same mutation and are born with a canine form of MTM. By adding back a healthy copy of the gene, Beggs’s collaborators got the dogs back on their feet running around again. (Read about Nibs, a female MTM carrier whose descendants took part in these studies.)
Based on the canine results, a clinical trial is now testing gene therapy in boys under the age of 5 with MTM. The phase I/II trial aims to enroll 12 boys and measure their respiratory and motor function and muscle structure after being dosed with a vector carrying a corrected MTM gene. In the meantime, observational and retrospective studies are characterizing the natural history of boys with MTM.
As the opioid epidemic deepens and drug overdoses increase, effective non-addicting painkillers are desperately needed. Efforts to discover new pain pathways to target with new drugs have thus far had little success. Other promising research is investigating triggerable local delivery systems for non-opioid nerve blockers, but it’s still in the early stages.
A new collaboration between Boston Children’s Hospital and the biopharmaceutical company Amgen is aimed at accelerating new pain treatments. Announced yesterday, it will revolve around patients with rare, perplexing pain syndromes. The scientists hope that the genetic variants they find in these patients will shed new light on pain biology and lead to new ways of controlling pain.…
Boys born with X-linked myotubular myopathy (XLMTM) face a grim prognosis. Extreme muscle weakness leaves many ventilator-dependent from birth, and most infants need feeding tubes. About half pass away before 18 months of age.
Last week, the biotechnology company Audentes Therapeutics announced the dosing of the first patient in a gene-therapy clinical trial — 21 years after the MTM1 gene was first cloned.
Hopes are high. Gene therapy has already shown striking benefits in dogs with XLMTM in studies co-authored by Alan Beggs, PhD, director of the Manton Center for Orphan Disease Research at Boston Children’s Hospital, and colleagues at Généthon and the University of Washington. In the most recent study, 10-week-old Labrador retrievers already showing signs of the disease showed improvements in breathing, limb strength and walking gait after a single dose of the gene therapy vector. …
At first, Corrie and Adam Mendes thought their daughter Emmie had an inner ear problem. She was late with several early milestones, including walking, and when she did walk, she often lost her balance. The family pediatrician sent them to a neurologist, who ordered a brain MRI and diagnosed her with pachygyria, a rare condition in which the brain is smoother than normal, lacking its usual number of folds.
Additionally, Emmie’s ventricles, the fluid-filled cushions around the brain, looked enlarged, so the neurologist recommended brain surgery to install a shunt to drain off fluid. He advised Corrie and Adam that Emmie’s life expectancy would be greatly reduced.
Back in the 1990s, rheumatologist Richard Weisbart, MD, of University of California, Los Angeles (UCLA), was studying lupus in a mouse model and found that the mice were making an antibody that had the intriguing ability to get inside tissues and cells.
Dustin Armstrong, PhD, a postdoc at Novartis at the time, was trying to find molecules that could activate growth in weakened muscles—without activating possibly cancerous growth in other tissues. He saw Weisbart’s work and contacted UCLA. In 2008, he obtained seed money and founded a company around 3E10-based therapeutics for muscular diseases, now known as Valerion Therapeutics (formerly 4s3 Bioscience).
“There’s a huge need for therapies for genetic muscle diseases, and muscle was a tissue we could target well with our technology,” says Armstrong. …
This two-part series examines two potential treatment approaches for myotubular myopathy, a genetic disorder that causes muscle weakness from birth.
Sixth-grader William Ward cruises the hallways at school with a thumb-driven power chair and participates in class with the help of a DynaVox speech device. Although born with a rare, muscle-weakening disease called X-linked myotubular myopathy, or MTM, leaving him virtually immobile, he hasn’t given up.
“From the very beginning, Alan connected with our family in a very human way,” says Will’s mother, Erin Ward. “In the scientific community, he’s been the bridge and the connector of researchers around the world. That makes him unique.”
Since the 1990s, Beggs has enrolled more than 500 patients with congenital myopathies from all over the world in genetic studies, seeking causes and potential treatments for congenital myopathies—rare, often fatal diseases that weaken children’s skeletal muscles from birth, often requiring them to breathe on a ventilator and to receive food through a gastrostomy tube. …