The hope to improve people’s lives is what drives many members of industry and academia to bring new products and therapies to market. At the BIO International Convention last week in Boston, there was lots of discussion about how translational science intersects with patients’ needs and why the best therapeutic developmental pipelines are consistently putting patients first.
“Our mission is to de-risk entry of new therapies in the ASD drug discovery and development space,” said Sahin, who is also a professor of neurology at Harvard Medical School.
One big challenge, says Sahin, is knowing how well — or how poorly — autism therapies are actually affecting people with ASD. Externally, ASD is recognized by its core symptoms of repetitive behaviors and social deficits. …
This is part I of a two-part blog series recapping the 2018 BIO International Convention.
At the 2018 BIO International Convention last week, it was clear what’s provoking scientific minds in industry and academia — or at least those of the Guinness-world-record-making 16,000 people in attendance. Artificial intelligence, machine learning and their implications for tailor-made medicine bubbled up across all BIO’s educational tracks and a majority of discussions about the future state of biotechnology. Panelists from Boston Children’s Hospital also contributed their insights to what’s brewing at the intersection of these burgeoning fields.
Isaac Kohane, MD, PhD, former chair of Boston Children’s Computational Health and Informatics Program, spoke on a panel about how large-scale patient data — if properly harnessed and analyzed for health and disease trends — is a virtual goldmine for precision medicine insights. Patterns gleaned from population health data or electronic health records, for example, could help identify which subgroups of patients who might respond better to specific therapies.
According to Kohane, who is currently the Marion J. Nelson Professor of Biomedical Informatics and Pediatrics at Harvard Medical School (HMS), we will soon be leveraging artificial intelligence to go through patient records and determine exactly what doctors were thinking when they saw patients.
“We’ve seen again and again that data abstraction by artificial intelligence is better than abstraction by human analysts when performed at the scale of millions of clinical notes across thousands of patients,” said Kohane.
And based on what we heard at BIO, artificial intelligence will revolutionize more than patient data mining. It will also transform the way we design precision therapeutics — and even vaccines — from the ground up. …
Since the late 1970s, biologists have known that blood develops in a specific body location. But they’ve wondered why different creatures house their blood stem cells in different places. In humans and other mammals, they’re in the bone. In fish, they’re in the kidney. Why?
Over-prescribing has long been thought to increase antibiotic resistance in bacteria. But could much bigger environmental pressures be at play?
While studying the role of climate on the distribution of antibiotic resistance across the geography of the U.S., a multidisciplinary team of epidemiologists from Boston Children’s Hospital found that higher local temperatures and population densities correlate with higher antibiotic resistance in common bacterial strains. Their findings were published today in Nature Climate Change.
“The effects of climate are increasingly being recognized in a variety of infectious diseases, but so far as we know this is the first time it has been implicated in the distribution of antibiotic resistance over geographies,” says the study’s lead author, Derek MacFadden, MD, an infectious disease specialist and research fellow at Boston Children’s Hospital. “We also found a signal that the associations between antibiotic resistance and temperature could be increasing over time.”
During their study, the team assembled a large database of U.S. antibiotic resistance in E. coli, K. pneumoniae and S. aureus, pulling from hospital, laboratory and disease surveillance data documented between 2013 and 2015. Altogether, their database comprised more than 1.6 million bacterial specimens from 602 unique records across 223 facilities and 41 states. …
Anti-seizure drugs don’t work in about a third of people with epilepsy. But for people with focal epilepsy, whose seizures originate in a discrete area of the brain, surgery is sometimes an option. The diseased brain tissue that’s removed also offers a rare opportunity to discover epilepsy-related genes.
Many mutations causing epilepsy have been discovered by testing DNA taken from the blood. But it’s becoming clear that not all epilepsy mutations show up on blood tests. So-called somatic mutations can arise directly in tissues like the brain during early prenatal development. Even within the brain, these mutations may affect only a fraction of the cells — those descended from the original mutated cell. This can create a “mosaic” pattern, with affected and unaffected cells sometimes intermingling.
One of the first such mutations to be described, by Ann Poduri, MD, MPH, and colleagues at Boston Children’s Hospital in 2012, was in Dante, a young boy who was having relentless daily seizures. The entire right side of Dante’s brain was malformed and enlarged, and he underwent a drastic operation, hemispherectomy, to remove it. Only later, studying brain samples from Dante and similar children, did Poduri find the genetic cause: a mutation in the gene AKT3. It affected only about a third of Dante’s brain cells. …
Pulmonary vein stenosis (PVS) is a rare disease in which abnormal cells build up inside the veins responsible for carrying oxygen-rich blood from the lungs to the heart. It restricts blood flow through these vessels, eventually sealing them off entirely if left untreated. Typically affecting young children, the most severe form of PVS progresses very quickly and can cause death within a matter of months after diagnosis.
Until recently, treatment options have been limited to keeping the pulmonary veins open through catheterization or surgery. Yet this approach only removes the cells but does nothing to prevent their regrowth. Now, a clinical trial shows that adding chemotherapy to a treatment regimen including catheterization and surgery can deter abnormal cellular growth and finally give children with PVS a chance to grow up.
“Through this approach, we’ve created the first-ever population of survivors who are living with severe PVS,” saysChristina Ireland, RN, MS, FNP, who has managed enrolling patients in the trial and treating new patients since the trial ended. “We’ve changed this disease from an acute killer to a chronic, manageable condition.” …
Interestingly, the same portal, known as the Frizzled receptor, also receives signals that maintain the intestine’s stem cells. When toxin B docks, it blocks these signals, carried by a molecule known as Wnt. But exactly how it all works remained a puzzle — until new research published today in Science.
Liang Tao, PhD in Dong’s lab, working with the labs of Rongsheng Jin, PhD, at UC-Irvine, and Xi He, PhD, at Boston Children’s, captured the crystal structure of a fragment of toxin B (in orange above) as it joined to the Frizzled receptor (in green). The structure revealed lipid molecules within the Frizzled receptor (in yellow and red) that play a central role. Normally, when Wnt binds to Frizzled, it nudges these lipids aside. But the team showed that when the toxin fragment binds to Frizzled, it locks these lipids in place, preventing Wnt from engaging with the cell.
Just as stem cells rely on Wnt signaling for growth and regeneration, so do many cancers. Now that its mechanism is known, Dong thinks this toxin B fragment, which by itself isn’t toxic, could be a useful anti-cancer therapeutic. They’re currently developing a new generation of Wnt signaling modulators and testing them in animal models of cancer. (For further information, contact Rajinder.Khunkun@childrens.harvard.edu of Boston Children’s Technology & Innovation Development Office.)
David Ludwig, MD, PhD, an endocrinologist at Boston Children’s Hospital, has written popular books espousing a low-glycemic, low-carbohydrate diet for weight control. He has argued that high-glycemic diets are contributing to the epidemic of type 2 diabetes. But he hadn’t given much thought to carbohydrate restriction for type 1 diabetes until 2016.
At a conference, Ludwig met a surgeon with type 1 diabetes who maintains normal hemoglobin A1c levels (indicating high blood sugar control) on a very-low-carbohydrate diet. This surprised and impressed him: he had never seen any patient with type 1 diabetes able to completely normalize their hemoglobin A1cs. Moreover, most diabetes experts discourage very-low-carb diets, believing they pose a risk for hypoglycemia, or a dangerous drop in blood sugar. …
Their plan is to optimize the ability for CAR T-cell therapies, which use a patient’s genetically modified T cells to combat cancer, to more specifically kill tumor cells without setting off an immune response “storm” known as cytokine release syndrome. The key ingredient is a unique small molecule that greatly enhances the specificity of the tumor targeting component of the therapy. …
Hutchinson-Gilford Progeria Syndrome, better known as progeria, is a highly rare genetic disease of premature aging. It takes a cruel toll: Children begin losing body fat and hair, develop the thin, tight skin typical of elderly people and suffer from hearing loss, bone problems, hardening of the arteries, stiff joints and failure to grow. They die at an average age of 14½, typically from heart disease resembling that of old age.