In many parts of the world, babies have just one chance to be vaccinated: when they’re born. Unfortunately, newborns’ young immune systems don’t respond well to most vaccines. That’s why, in the U.S., most immunizations start at two months of age.
Currently, only BCG, polio vaccine and hepatitis B vaccines work in newborns, and the last two require multiple doses. But new research raises the possibility of one-shot vaccinations at birth — with huge implications for reducing infant mortality. …
Some 10 to 15 percent of people with asthma have severe disease that medications can’t control. A deep-dive multicenter study finds differences in these patients’ immune systems that may explain why increased dosages of corticosteroids don’t help — and could lead to steroids doing more harm than good. Findings appear online this week in Science Immunology. …
Tim Yu, MD, PhD, a neurologist and genomics researcher at Boston Children’s Hospital, was studying autism genes when he saw something on a list that rang a bell. It was a mutation that completely knocked out the so-called Deleted in Colorectal Carcinoma gene (DCC), originally identified in cancer patients. The mutation wasn’t in a patient with autism, but in a control group of patients with brain malformations he’d been studying in the lab of Chris Walsh, MD, PhD.
Yu’s mind went back more than 20 years. As a graduate student at University of California, San Francisco, he’d conducted research in roundworms, studying genetic mutations that made the worms, which normally move in smooth S-shaped undulations, move awkwardly and erratically. …
Gene therapy stalled in the early 2000s as adverse effects came to light in European trials (leukemias triggered by the gene delivery vector) and following the 1999 death of U.S. patient Jesse Gelsinger. But after 30 years of development, and with the advent of safer vectors, gene therapy is becoming a clinical reality. It falls into two main categories:
In vivo: Direct injection of the gene therapy vector, carrying the desired gene, into the bloodstream or target organ.
Ex vivo: Removal of a patient’s cells, treating the cells with gene therapy, and reinfusing them back into the patient, as in hematopoietic stem cell transplant and CAR T-cell therapy.
In honor of Rare Disease Day (Feb. 28), we salute “citizen scientists” Jocelyn and John Duff.
When Talia Duff was born, her parents realized life would be different, but still joyful. They were quickly adopted by the Down syndrome parent community and fell in love with Talia and her bright smile.
But when Talia was about four, it was clear she had a true problem. She started losing strength in her arms and legs. When she got sick, which was often, the weakness seemed to accelerate.
Talia was initially diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), an autoimmune disease in which the body attacks its own nerve fibers. Treated with IV immunoglobulin infusions to curb the inflammation, she seemed to grow stronger — but only for a time. Adding prednisone, a steroid, seemed to help. But it also caused bone loss, and Talia began having spine fractures.
“We tried a lot of different things, but she never got 100 percent better,” says Regina Laine, NP, who has been following Talia in Boston Children’s Hospital’s Neuromuscular Center the past several years, together with Basil Darras, MD. “That’s when we decided to readdress the possibility that it was genetic.” …
For more than two decades, Alan Beggs, PhD, at Boston Children’s Hospital has explored the genetic causes of congenital myopathies, disorders that weaken children’s muscles, and investigated how the mutations lead to muscle weakness. For one life-threatening disorder, X-linked myotubular myopathy (XLMTM), the work is approaching potential payoff, in the form of a clinical gene therapy trial.
Boys with XLMTM are born so weak that they are dependent on ventilators and feeding tubes to survive. Almost half die before 18 months of age. …
The global theme of this year’s Rare Disease Day (February 28) is research, and in keeping with that, we salute a very important group of people: citizen scientists. These can-do patients and family members are putting previously undiagnosed rare diseases on the map and driving the search for treatments. Citizen scientists play multiple roles: They keep scientists focused on therapeutic development, conduct online research to connect ideas, set up patient networks and data registries, raise money and start companies. They’ve earned a voice in clinical trial design and were instrumental in the passage of the 21st Century Cures Act.
Meet a few citizen scientists who have inspired us recently. …
Abraham Rudolph, MD, who recently turned 93, has watched his chosen corner of the medical profession — pediatric cardiology — grow from rudimentary beginnings into a robust, multivariate discipline. Yet while his name is known worldwide in pediatric cardiology circles, he entered cardiology more than 50 years ago only by happenstance.
Born in South Africa in 1924, Rudolph came to the United States in 1951 to train in cardiology by invitation of Charles Janeway, MD, then Physician-in-Chief at Boston Children’s Hospital. Concerned about providing for his wife and newborn daughter, he chose cardiology over hematology or neurology because it offered a salary; many other physician-training opportunities at the time were unpaid. That first year, as the hospital’s first cardiology fellow, he made $3,000 — thanks to a family donation.
He stayed on for nine years, becoming director of the cardiac catheterization laboratory. There he found his focus.
“I became more and more interested in the physiology of the circulation, particularly the problems surrounding infancy,” he said in a 1996 interview with the American Academy of Pediatrics. “At that time, there were relatively few places that were doing anything about infants with heart disease. Most of the emphasis was on older children.” …
Tuberous sclerosis complex (TSC) strikes about 1 in 6,000 people and is marked by numerous benign tumors in the brain, kidneys, heart, lungs and other tissues. Children with TSC often have epilepsy, intellectual disability and/or autism, showing disorganized white matter in their brains. Work in the lab of Mustafa Sahin, MD, PhD, has shown that the TSC1 mutation disrupts the brain’s ability to adequately wrap its nerve fibers in myelin, the insulating coating that enhances nerves’ ability to conduct signals. A new study from the lab shows why: neurons lacking functional TSC1 secrete increased amounts of connective tissue growth factor (CTGF). This impairs the development of oligodendrocytes, the cells that do the myelinating. Here, electron microscopy in a TSC mouse model shows a decreased number of nerve fibers wrapped in myelin (dark ovals) on the left. On the right, genetic deletion of CTGF increases myelination. Sahin plans to delve further to develop potential pharmaceutical approaches to restore myelination in TSC. Read more in the Journal of Experimental Medicine. (Image: Ebru Ercan et al.)
Diamond Blackfan anemia (DBA) has long been a disease waiting for a cure. First described in 1938 by Louis K. Diamond, MD, of Boston Children’s Hospital and his mentor, Kenneth Blackfan, MD, the rare, severe blood disorder prevents the bone marrow from making enough red blood cells. It’s been linked to mutations affecting a variety of proteins in ribosomes, the cellular organelles that themselves build proteins. The first mutation was reported in 1999.
But scientists have been unable to connect the dots and turn that knowledge into new treatments for DBA. Steroids are still the mainstay of care, and they help only about half of patients. Some people eventually stop responding, and many are forced onto lifelong blood transfusions.
Researchers have tried for years to isolate and study patients’ blood stem cells, hoping to recapture the disease process and gather new therapeutic leads. Some blood stem cells have been isolated, but they’re very rare and can’t be replicated in enough numbers to be useful for research.
Induced pluripotent stem (iPS) cells, first created in 2006 from donor skin cells, seemed to raise new hope. They can theoretically generate virtually any specialized cell, allowing scientists model a patient’s disease in a dish and test potential drugs.
There’s been just one hitch. “People quickly ran into problems with blood,” says hematology researcher Sergei Doulatov, PhD. “iPS cells have been hard to instruct when it comes to making blood cells.” …