New tools and technologies fueled biomedicine to great heights in 2017. Here are just a few of our top picks. All are great examples of research informing better care for children (and adults).
1. Gene therapy arrives
In 2017, gene therapy solidly shed the stigma of Jesse Gelsinger’s 1999 death with the development of safer protocols and delivery vectors. Though each disease must navigate its own technical and regulatory path to gene therapy, the number of clinical trials is mounting worldwide, with seven gene therapy trials now recruiting at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. In August, the first gene therapy won FDA approval: CAR T-cell therapy for pediatric acute lymphoblastic leukemia. This “ex vivo” form of gene therapy, now being offered at Dana-Farber/Boston Children’s, treats patients’ T cells outside the body, then reinfuses them to enhance the body’s immunologic attack on the cancer. In October, Dana-Farber/Boston Children’s researchers announced in The New England Journal of Medicine that gene therapy had halted cerebral adrenoleukodystrophy, the debilitating brain disease depicted in the movie “Lorenzo’s Oil,” in 15 of 17 boys. The ability to route gene therapy directly into the brain, reported earlier this month, offers even more promise for treating central nervous system diseases and neurodegenerative disorders that are genetic or metabolic in origin.
2. Stem-cell-based therapeutic possibilities expand
In May, Boston Children’s Stem Cell Research program achieved a goal that’s been held for more than 20 years: making blood stem cells in the lab from patients’ own cells. Blood stem cell transplants can rebuild the body’s blood system and even reboot it, treating certain cancers, blood disorders, immune deficiencies and even metabolic disorders. The ability to derive blood stem cells from patients’ own cells eliminates the need to find a matched donor and makes transplant safer and less toxic.
Blood disorders aren’t the only diseases to potentially benefit. Separate Boston Children’s studies in November and December found that pre-treated blood stem cells reverse type 1 diabetes in mice and demonstrated the potential from blood stem cells, delivered into the brain, to treat lysosomal storage disorders, severe metabolic disorders that affect the central nervous system.
Other types of stem cells also showed promise. A Boston Children’s study published in October found that fetal mesenchymal stem cells isolated from amniotic fluid, multiplied in the lab and reinfused into the womb, make their way to the fetal bone marrow. The cells had previously been shown to treat certain birth defects like spina bifida that are in contact with the amniotic fluid. The surprising new finding suggests the possibility of also treating unexposed defects, like congenital diaphragmatic hernia or even blood disorders, before a baby is even born.
3. Genome-based treatment of childhood cancers
In 2017, the buzz around “precision medicine” became a firm reality for pediatric cancer. Brain tumors have led the way, with molecular “signatures” first characterized in 2002 by Boston Children’s researchers. In January, a comprehensive dataset compiled by a multi-institutional team including Dana-Farber/Boston Children’s revealed just how diverse and individual childhood cancers are. Even within a tumor subtype, tumors can arise from different genetic mutations. In fact, genomic profiling can trump standard tumor classification schemes, pointing to more effective therapies.
Arising from this work, the first-of-its kind Pediatric MATCH trial is now offering nationwide genetic profiling services to pediatric and young adult cancer patients across the U.S. Patients’ tumors will be screened for more than 160 cancer-related mutations in order to match them with a targeted therapy.
4. Gene editing emerges as powerful discovery tool
With the first editing of the genome directly in the body reported in November, therapeutic gene editing will explode in 2018. But gene editing is also a powerful tool for scientific discovery, enabling researchers to systematically delete or alter genes to find which ones are important to disease. Boston Children’s researchers employed it in 2017 to investigate a rare kidney disorder, intestinal C. difficile infection and Sturge Weber syndrome. In July, using CRISPR-Cas9 gene editing, researchers at Dana-Farber/Boston Children’s deleted thousands of tumor genes to test their function in mice. The exercise revealed new potential targets to enhance the effectiveness of PD-1 checkpoint inhibitors, a promising new class of cancer immunotherapy.
5. Hope for hydrocephalus
Hydrocephalus, or “water on the brain,” often requires children to have a shunt implanted to drain the excess cerebrospinal fluid. Unfortunately, shunts have a tendency to plug up, requiring emergency surgery to correct or replace the shunt. 2017 saw two exciting advances that could spare children from a lifetime of shunt operations. In November, the FDA cleared a shunt-flushing device originally conceived at Boston Children’s that allows doctors to clear many blockages in the office, with the press of a button. And just last week, a clinical trial in The New England Journal of Medicine showed good results with a one-time operation for hydrocephalus that could avoid the need for shunting altogether. Its developer at Boston Children’s is training surgeons around the world in the operation, with the help of an ultra-high-fidelity model co-created with Hollywood special effects artists.
6. Robotics and biomaterials advance pediatric cardiology
Boston Children’s Heart Center reported several innovations this year. A proof-of-concept study showed in January that robotic device, hugging a failing heart, can provide the natural twist and squeeze of normal ventricular contractions. A follow-up study in November showed that the device can be adapted for single-sided heart failure. These devices do not come into contact with a patient’s blood, unlike other implantable ventricular assist devices that require patients to take anti-clotting medications. They were co-developed with Harvard’s School of Engineering and Applied Sciences and the Wyss Institute for Biologically Inspired Engineering. Additional devices included a sticky, stretchy, slug-inspired adhesive for cardiac repairs and a growth-accommodating implant for use in valve annuloplasty, a procedure that repairs leaking mitral and tricuspid valves in the heart, inspired by the braided, expanding design of a Chinese finger trap.
7. Opening up the brain to drugs
Researchers found a way to selectively control openings in the blood-brain barrier to allow passage of small drug molecules, potentially enabling the treatment of hard-to-reach neurodegenerative and neuroinflammatory diseases and neurological cancers.
8. What fuels autoimmunity’s runaway train
A discovery reported in August could change the way we look at autoimmune diseases and our understanding of how and why immune cells begin to attack different tissues in the body. It revealed how rogue B cells — which produce antibodies and program the immune system to attack certain antigens — can trigger an “override” that launches the body into attacking its own tissues as if responding to a foreign pathogen.
9. Moving closer to a blood test to determine SIDS risk
In postmortem studies spanning more than a decade, Boston Children’s researchers have linked sudden infant death syndrome with abnormally-decreased serotonin levels in the brainstem. In July 2017, the team found a link between SIDS death and increased blood levels of serotonin in certain babies. This finding provides hope SIDS risk could be detected in live newborn infants and avoided through preventive measures.
10. Man’s best medical friend?
Thanks to partnerships with veterinary researchers, dogs have led scientists to new treatment leads for osteosarcoma, Duchenne muscular dystrophy and X-linked myotubular myopathy, for which a human gene therapy trial is now beginning.
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