David Williams, MD, the principal investigator of the clinical trial, discusses gene therapy and its impact on children with adrenoleukodystrophy
Adrenoleukodystrophy — depicted in the 1992 movie “Lorenzo’s Oil” — is a genetic disease that most severely affects boys. Caused by a defective gene on the X chromosome, it triggers a build-up of fatty acids that damage the protective myelin sheaths of the brain’s neurons, leading to cognitive and motor impairment. The most devastating form of the disease is cerebral adrenoleukodystrophy (CALD), marked by loss of myelin and brain inflammation. Without treatment, CALD ultimately leads to a vegetative state, typically claiming boys’ lives within 10 years of diagnosis.
The Center for Disease Control estimates that influenza virus–related illnesses account for more than 200,000 U.S. hospitalizations and 12,000 deaths annually. Young children, the elderly and people with respiratory, cardiac and other chronic health conditions are at particularly high risk for being hospitalized for influenza-related complications. Until now, there has not been a clear reason to explain why some individuals become severely ill from flu and not others.
New findings published in Nature Medicine, however, might change that.
“We’ve identified a genetic variant that we believe may put people at risk of getting life-threatening influenza infections,” says Adrienne Randolph, MD, MSc, a senior associate in pediatric critical care medicine at the Boston Children’s Hospital. …
Recently announced preliminary results of the BabySeq study included pathogenic or “likely pathogenic” variants linked to heart conditions in three apparently healthy babies. Two are being followed at Boston Children’s Hospital and have had cardiac testing. But is this testing necessary, and are these infants truly at risk? It’s too soon to tell.
Then, last week, a report from the Mayo Clinic raised an alarm about overzealous use of genetic testing in healthy individuals. After a 13-year-old boy died from a heart syndrome, about two dozen family members had genetic testing. All tested positive for variants in a gene linked to long-QT syndrome and were diagnosed with the disease. Yet none had cardiac symptoms, and only one had a positive EKG at any point — the boy’s brother, who had a defibrillator implanted. When the Mayo team reanalyzed the test results using a more up-to-date genetic database, they concluded the variant is harmless.
And this week, in Science Translational Medicine, researchers at Brigham and Women’s Hospital, Boston Children’s and Massachusetts General Hospital address the question: If people carry a genetic mutation linked to a condition, what are the chances they will develop that condition over time? As part of the genomes2people project, the researchers tested participants in two long-term population studies — the Framingham Heart Study and the Jackson Heart Study — for 56 genes representing 24 hereditary cancer and cardiac syndromes. They did not know the participants’ actual health status. As it turned out, carrying a mutation increased risk for the related disease 4.7-fold in African Americans and 6.4-fold in European Americans, who had longer follow-up. This was true regardless of family history.
Vector sat down with Nina Gold, MD, a senior resident in Pediatrics and Medical Genetics at Boston Children’s, for her perspective. Gold is a first author on this week’s report. …
Nicole D. Kling, PhD, is a patent specialist at Nixon Peabody LLP who focuses on patent prosecution in biotechnology, the life sciences and biomedical advances. David Resnick, JD, of Nixon Peabody contributed to this post. Opinions expressed in this article represent only those of the authors, not Nixon Peabody or its clients.
The recent ruling by the U.S. Supreme Court brought Association for Molecular Pathology v. Myriad Genetics back to the headlines, with interest being stoked by Angelina Jolie’s recent disclosure of her double mastectomy.
The lawsuit revolved around patents owned by Myriad related to its BRACAnalysis test, which assesses the likelihood that a person will develop certain cancers, including breast cancer, by searching the DNA for disease-causing sequences. The patents under focus in this lawsuit claim genetic sequences isolated from, or derived from, human DNA—molecules created by manipulating, changing or adding to the DNA.
Myriad argued that the molecules they claimed do not exist as such in human cells and are instead the result of human manipulation and innovation. …
Though autism can respond well to early behavioral interventions, it’s typically not diagnosed in the U.S. until around age 5, when these interventions are less effective. Autism is diagnosed based on a child’s behaviors and language, which take time to develop to the point where clinicians can reliably assess them. What’s really needed is a fast, objective test when a child is much younger, before symptoms even show up.
In the past decade, researchers have chipped away at the problem, linking more than a dozen genetic mutations to autism—from small DNA “spelling” changes to lost or extra copies of a gene or genes (known as copy number variants) to wholesale chromosome abnormalities. Tests have been created, such as the chromosomal microarray test. But together, the known mutations account for, at best, 1 in 5 autism cases among tested patients. …
It’s been more than a decade since the Human Genome Project cracked our genetic code. DNA sequencing is getting cheaper and cheaper. So why isn’t it being used every day in medicine?
The truth is that while we have the technology to blow apart a patient’s DNA and piece it back together, letter by letter, and compare it with normal “reference” DNA, doctors don’t really know what to do with this information. How much of it is really relevant or useful? Should they be giving it back to patients and their families, and how?
Handled badly, the information could do more harm than good. “We don’t want to scare patients for no reason, or for the wrong reason,” says Isaac Kohane, MD, PhD, who chairs the Children’s Hospital Informatics Program.
Seeking a set of best practices for safe, clinically useful genomic sequencing, Boston Children’s Hospital took a crowd-sourcing approach. …
Sequencing a patient’s genome to figure out the exact source of his or her disease isn’t standard operating procedure — yet. But falling sequencing costs and a growing number of successes are starting to bring this approach into the mainstream, helping patients and families while advancing a broader understanding of their diseases.
The Stone family is a case in point. When John and Warren Stone were born, their parents were envisioning life raising identical twins, when suddenly everything changed. On their second day of life, the twins started to have seizures with stiffening of their arms and legs; more alarmingly, they would stop breathing from time to time, requiring a ventilator to help them breathe. Further work-up revealed that both John and Warren were having persistent seizures consistent with Ohtahara syndrome, a rare, debilitating seizure disorder.
Warren died a few weeks later, and the family transferred John’s care to Boston Children’s Hospital. An extensive clinical and genetic work-up here and at several other hospitals involved in his care — including sequencing all the genes known to cause Ohtahara syndrome – identified no cause for John’s unique seizures. …
How do you find the genetic cause of a disease that doesn’t appear to be inherited, presents with a variety of symptoms—and has been diagnosed in just a few hundred people worldwide? Add to that the fact that the genetic defect occurs in only a portion of a patient’s cells, and a formidable challenge emerges.
It all started in 2006. That’s when, after poring over years’ worth of patient records and photos, Ahmad Alomari, MD, an interventional radiologist at Boston Children’s and co-director of its Vascular Anomalies Center, defined a condition he called CLOVES syndrome. CLOVES is complex and looks somewhat different in every patient, causing a combination of vascular, skin, spinal and bone or joint abnormalities. It’s a rare and progressive disease for which no known cure or “one-size-fits-all” treatment exists. …
When I tell people I work at the Technology and Innovation Development Office at Children’s (TIDO), they usually think I work to commercialize patented blockbuster drug candidates. But many of the most satisfying projects I help promote are innovations that don’t involve as much risk, time and investment, yet make a big difference for patients. Commercializing these innovations can help the greater good, and is part of what propels me to work at a licensing office at a pediatric hospital.
And sometimes it doesn’t take much to help them along.
As an Ashkenazi Jew planning to have a baby, I sure as heck wanted carrier screening for Tay-Sachs disease. But that disease is incurable and lethal. What about diseases that don’t severely limit lifespan and aren’t that disabling? During my pregnancy, I went on to have amniocentesis, which included testing for Down syndrome and – because of my family history — for a few genes associated with autism and mental retardation. But even as I was tested, I had no idea what I’d do if results came back positive.