Part 2 of a two-part series. (Read part 1.)
Joshua Frase, who died from X-linked myotubular myopathy (MTM), with his father, Paul Frase, in 2006.
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.
Weisbart shifted his work away from studying lupus to studying and refining the antibody, called 3E10, and he and others showed that proteins could be delivered into different tissues of the body simply by attaching them to a fragment of 3E10.
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. Full story »
Will Ward at the NSTAR Walk for Boston Children’s Hospital in 2012—his family’s fifth year leading a team to raise funds for the Beggs Laboratory.
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.
Neither has Alan Beggs, PhD, who directs the Manton Center for Orphan Disease Research at Boston Children’s Hospital, and who has known Will since he was a newborn in intensive care.
“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. Full story »
Ed. Note: Leonard Zon, MD, is founder and director of the Boston Children’s Hospital Stem Cell Program, which yesterday was awarded $4 million by the Massachusetts Life Sciences Center to build the Children’s Center for Cell Therapy.
Leonard Zon (top) and Massachusetts Lt. Governor Timothy Murray in the Stem Cell Program's zebrafish facility. (Courtesy MLSC)
As a hematologist, I see all too many children battling blood disorders that are essentially untreatable. Babies with immune deficiencies living life in a virtual bubble, hospitalized again and again for infections their bodies can’t fight. Children disabled by strokes caused by sickle cell disease, or suffering through sickle cell crises that drug treatments can’t completely prevent. Children whose only recourse is to risk a bone marrow transplant—if a suitably matched donor can even be found.
Over the past 20 years, my lab and that of George Daley, MD, PhD, at Boston Children’s Hospital have worked hard to give these children a one-time, potentially curative option—a treatment that begins with patients’ own cells and doesn’t require finding a match. Full story »
Vector has been deliberating about its predictions for 2013, consulting its many informants. Here’s where we’re putting our money this year; if you have other ideas, scroll to the bottom and let us know.
Genome sequencing scaling up at health care institutions
Last year we predicted genome sequencing’s entry into the clinic; this could be the year it goes viral. Technology companies with ever-faster sequencers and academic medical centers are teaming up at a brisk pace to offer genomic tests to patients. Just in the past two weeks, a deal was announced between The Children’s Hospital of Philadelphia and BGI-Shenzhen to sequence pediatric brain tumors; Partners HealthCare and Illumina Inc. announced a network of genomic testing laboratories; Full story »
A new spinoff business will make large-scale genomic diagnostics a reality in medical practice (Image: Rosendahl)
Genomic sequencing and molecular diagnostics are becoming a global business. At the recent American Society of Human Genetics meeting, dazzling technologies for reading genetic code were on display—promising faster, cheaper, sleeker.
Nevertheless, it’s become clear that the ability to determine someone’s DNA or RNA sequence doesn’t automatically translate into useful diagnostics or even actionable information. In fact, the findings are often confusing and hard to interpret, even by physicians.
That’s where academic-industry partnerships can flourish—tapping the deep expertise of medical research centers to bring clinical meaning to sequencing findings. Yesterday, Boston Children’s Hospital and Life Technologies Corp. announced a new venture with a great list of ingredients: fast, accurate, scalable sequencing technology—Life’s Ion Proton® Sequencer—but also research and clinical experience in rare and genetic diseases, bioinformatics expertise to handle the big data, and the medical and counseling expertise to create meaning from the results. Full story »
What will happen to medically complex children if insurance coverage is reduced and fewer pediatricians are trained to care for them? (Image: Wikimedia Commons)
Jay Berry, MD, MPH, is a pediatrician and hospitalist in the Complex Care Service at Boston Children’s Hospital. His most recent research appears in the JAMA Pediatrics, accompanied by editorials on the findings’ implications for health care and residency training. Berry further discusses its implications in this podcast.
My first encounter with a children’s hospital was as a first grader in 1980, when my 5-year-old cousin was diagnosed with cancer. Although her family was challenged to afford her cancer treatments, St. Jude Children’s Hospital in Memphis welcomed her and treated her cancer into remission. I remember my parents saying, “Everybody in that hospital loves children. No child is turned away.”
In 1997, walking into the Children’s Hospital of Alabama as a medical student, I felt the same sense of hope and courage. Everyone on the staff believed that they could make a difference in the lives of the children and families, despite the horrific illnesses that many of the children endured. I knew, immediately, that I wanted to become a pediatrician and to learn how to care for sick children. Full story »
Mice with the mutation causing Rett syndrome (middle panel) have an excess of inhibitory connections as compared with normal mice (left panel) and mutated mice reared with no visual stimulation (right panel). Inhibitory connections were also reduced by manipulating the NMDA receptor, restoring a more normal balance of inhibition/excitation.
Research just published in Neuron offers some interesting clues about Rett syndrome, a tragic disease that causes initially healthy girls to lose their ability to speak and to develop motor and respiratory problems. Working with a mouse model, the Boston Children’s Hospital lab of Michela Fagiolini, PhD, explored how the causative mutations, affecting the MECP2 gene, disrupt brain circuitry and function. The team found that the circuit damage can be undone by targeting the NMDA receptor, tipping the brain toward the right balance of inhibition and excitation. They’re now exploring possible pharmaceutical approaches.
The study also suggests that changes in the visual system are a tip-off to what’s going on in the brain as a whole. Full story »
Agustín Cáceres, once a virtual "bubble boy," is no longer on infectious disease precautions.
For the Cáceres family of Argentina, it’s a joyous holiday homecoming. Agustín, who received gene therapy at 5½ months of age, journeyed with his family to Boston for a check-up and got a clean bill of health.
Agustín was born with the rare immune-deficiency disorder SCID-X1. More popularly known as “bubble boy” disease, it left him defenseless against infections, unable to make enough T-cells to fight them off. His baptism was the only time his family could come near him, all wearing masks, gloves and gowns. His infancy was spent in isolation with his mother.
Now, at age 2½, Agustín has been cleared to go to nursery school, ride a bus and attend large family gatherings without fear of contracting a life-threatening infection. When we caught up with him, he was chasing and tumbling with his older brother Jeremías while waiting to bid farewell to his care team. Full story »
Colombian twins Miranda and Olivia Agudelo (with their parents) were the first patients in a clinical trial aimed at making the bone marrow transplant process less toxic.
One thing that most people don’t realize about stem cell transplants (also called bone marrow or hematopoietic stem cell transplants) is that for patients, the transplant itself is probably the easiest part of the process. The grueling part is the preparation for a transplant, called conditioning.
There’s been a lot done at Dana-Farber/Children’s Hospital Cancer Center (DF/CHCC) and elsewhere to make conditioning less toxic. With a new clinical trial in a rare genetic syndrome called dyskeratosis congenita (DC), doctors at DF/CHCC are taking an even bolder step. Full story »