In 1938, Louis K. Diamond, MD, and Kenneth Blackfan, MD, at Boston Children’s Hospital described a severe congenital anemia that they termed “hypoplastic” (literally, “underdeveloped”) because of the bone marrow’s inability to produce mature, functioning red blood cells. Eighty years later, the multiple genetic origins of this highly rare disease, now known as Diamond-Blackfan anemia, or DBA, are finally coming into view.
In 2004, a surgeon and a hospital pharmacist went against the prevailing dogma. They began revising the IV nutrition formula being given to children unable to take food by mouth. In doing so, they saved many lives. Yet, it wasn’t until last month that their intervention, a new fat emulsion called Omegaven, gained formal approval from the Food and Drug Administration.
Children with intestinal failure due to gastroschisis, necrotizing enterocolitis or other diseases are typically placed on parenteral nutrition, an intravenous method of feeding. Without it, they would die. But prolonged use of IV nutrition — using the traditional formula — had a massive side effect: injury to the liver. The majority of children either died from liver failure or required a liver transplant.
By 2001, surgeon Mark Puder, MD, at Boston Children’s Hospital was tired of watching babies slowly die from liver disease that should be preventable. He suspected something needed to be adjusted in the IV nutrition formula — particularly the fat component, derived from soybean oil and known as Intralipid. …
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. …
For more than 15 years, pediatric neuro-oncologist Mariella Filbin, MD, PhD, has been on a scientific crusade to understand DIPG (diffuse intrinsic pontine glioma). She hopes to one day be able to cure a disease that has historically been thought of as an incurable type of childhood brain cancer.
“While I was in medical school, I met a young girl who was diagnosed with DIPG,” Filbin recalls. “When I heard that there was no treatment available, I couldn’t believe that was the case. It really made a huge impression on me and since then, I’ve dedicated all my research to fighting DIPG.”
Her mission brought her to Boston Children’s Hospital for her medical residency program and later, to do postdoctoral research at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. Now, she’s starting her own research laboratory focused on DIPG — which has also been called diffuse midline glioma (DMG) in recent years — and continuing to treat children with brain tumors at the Dana-Farber/Boston Children’s pediatric brain tumor treatment center. She’s also a scientist affiliated with the Broad Institute Cancer Program.
This year, Filbin has made new impact in the field by leveraging the newest single-cell genetic sequencing technologies to analyze exactly how DIPG develops in the first place. Her latest research, published in Science, entailed profiling more than 3,300 individual brain cells from biopsies of six different patients.
Using what’s known as a single-cell RNA sequencing approach to interrogate the makeup of DIPG/DMG tumors, Filbin was able to identify a particularly problematic type of brain cell that acts forever young, constantly dividing over and over again in a manner similar to stem cells. …
During the 1918 influenza pandemic, the average life expectancy in the U.S. dropped below 40 years old. Today, public health and medical professionals need to be actively preparing for the next great pandemic, according to leaders of the Massachusetts Medical Society, The New England Journal of Medicine and Microsoft founder Bill Gates, who delivered the keynote address at a Boston-based meeting on April 27 called Epidemics Going Viral: Innovation vs. Nature. Here’s recap of what we heard from various panelists.
The five key drivers of epidemics are population growth/urbanization, travel, animals, environmental/climate changes and conflicts/natural disasters, according to Harvey Fineberg, MD, PhD, President of the Gordon and Betty Moore Foundation and former president of the Institute of Medicine. When it comes to predicting and preventing the next epidemic, Fineberg believes that data from a social media platform like Twitter isn’t going to help identify the next big outbreak.
But John Brownstein, PhD, an epidemiologist and Chief Innovation Officer at Boston Children’s Hospital, disagreed with that idea.
“I believe it’s possible for Twitter to find the next microbe,” Brownstein said. “This information comes in real time and at global scale.” Attendees who were live tweeting with the hashtag #epidemicsgoviral were quick to highlight this difference of opinion.
Uber flu shot, “a cool millennial thing to do”
Anne Schuchat, MD, deputy director of the Centers of Disease Control, busted the myth that non-vaccination rates are rising. She explained that media stories about anti-vaccination supporters can make it seem as though vaccination rates are falling when they actually aren’t.
“Less than one percent of kids aren’t vaccinated in the U.S.,” Schuchat said.
But some vaccinations, like the annual flu shot, still have big gaps to close. Brownstein described how a partnership with Uber — dispatching flu vaccines and nurses to people’s homes — was able to influence people to get their first-ever flu shot. …
What drives me as a scientist has changed over the course of my career. It was my fascination with experimentation that first got me interested in biology. In high school, I took vials of fruit flies to a radiation oncology department and tested the effects of radiation on the mutation rate. When I came to the U.S. to study biochemistry in college, I was drawn to the mysteries of the brain. While my PhD and postdoctoral work continued on very fundamental questions about how neurons connect to each other, advances in genetics and neuroscience allowed me to bring rigorous basic science approaches to clinical questions. So more and more, my science is driven by a need to bring treatments to the patients I see in the clinic. Fortunately, this is no longer a long-term, aspirational goal, but something within reach in my career. …
By taking a deep dive into the molecular underpinnings of Diamond-Blackfan anemia, scientists have made a new discovery about what drives the development of mature red blood cells from the earliest form of blood cells, called hematopoietic (blood-forming) stem cells.
For the first time, cellular machines called ribosomes — which create proteins in every cell of the body — have been linked to blood stem cell differentiation. The findings, published today in Cell, have revealed a potential new therapeutic pathway to treat Diamond-Blackfan anemia. They also cap off a research effort at Boston Children’s Hospital spanning nearly 80 years and several generations of scientists.
Diamond-Blackfan anemia — a severe, rare, congenital blood disorder — was first described in 1938 by Louis Diamond, MD, and Kenneth Blackfan, MD, of Boston Children’s. The disorder impairs red blood cell production, impacting delivery of oxygen throughout the body and causing anemia. Forty years ago, David Nathan, MD, of Boston Children’s determined that the disorder specifically affects the way blood stem cells become mature red blood cells.
Then, nearly 30 years ago, Stuart Orkin, MD, also of Boston Children’s, identified a protein called GATA1 as being a key factor in the production of hemoglobin, the essential protein in red blood cells that is responsible for transporting oxygen. Interestingly, in more recent years, genetic analysis has revealed that some patients with Diamond-Blackfan have mutations that block normal GATA1 production.
Now, the final pieces of the puzzle — what causes Diamond-Blackfan anemia on a molecular level and how exactly ribosomes and GATA1 are involved — have finally been solved by another member of the Boston Children’s scientific community, Vijay Sankaran, MD, PhD, senior author of the new Cell paper. …
The basic biological mechanisms that underpin autoimmune disorders are finally coming to light. Researchers in Boston’s Longwood medical area — a neighborhood where the streets are flanked by hospitals, research institutions and academic centers — are setting the stage for a new wave of future therapies that can prevent, reduce or even reverse symptoms of disease.
Inside the lab of Michael Carroll, PhD, scientists are working to understand how and why immune cells start to attack the body’s own tissues; it turns out the immune system’s B cells compete with each other in true Darwinian fashion. On the way to this discovery, the lab has flushed out new potential drug targets that could ease autoimmune symptoms — or stop them entirely — by “resetting” the body’s tolerance to itself.
The implications for a link between inflammation and synapse loss go beyond lupus because inflammation underpins so many diseases and conditions, ranging from Alzheimer’s to viral infection and even to to chronic stress. In which case, are we all losing synapses to some varying degree? Carroll plans to find out.
“We’ve found that chronic inflammation and autoinflammatory disorders can originate from genetic mutations to MDA5 that cause it to misrecognize ‘self’ as ‘non-self,’ essentially launching the immune system into self-attack mode,” said Hur. …
Will Ward’s birthday falls on Rare Disease Day (Feb. 28). That’s an interesting coincidence because he has a rare disease: X-linked myotubular myopathy (MTM), a rare, muscle-weakening disease that affects only boys. Originally on Snapchat, this video captures the Ward family’s recent visit to the lab of Alan Beggs, PhD to learn more about MTM research.
Beggs, director of the Manton Center for Orphan Disease Research at Boston Children’s Hospital, has known Will since he was a newborn in intensive care. In this lab walk-though you’ll see a freezer filled with muscle samples, stored in liquid nitrogen; muscle tissue under a microscope; gene sequencing to identify mutations causing MTM and other congenital myopathies and a testing station to measure muscle function in samples taken from animal models.
Beggs’s work, which began more than 20 years ago, led to pivotal studies in male Labrador retrievers who happen to have the same mutation and are born with a canine form of MTM. By adding back a healthy copy of the gene, Beggs’s collaborators got the dogs back on their feet running around again. (Read about Nibs, a female MTM carrier whose descendants took part in these studies.)
Based on the canine results, a clinical trial is now testing gene therapy in boys under the age of 5 with MTM. The phase I/II trial aims to enroll 12 boys and measure their respiratory and motor function and muscle structure after being dosed with a vector carrying a corrected MTM gene. In the meantime, observational and retrospective studies are characterizing the natural history of boys with MTM.
The 2018 Winter Olympics have brought nearly 3,000 delegates from 206 countries together in PyeongChang, South Korea. But just a week after kicking off on February 8, the games and its attendees are already being interrupted by a fast-spreading norovirus outbreak.
Norovirus is an extremely infectious disease transmitted through food, water or by touching a contaminated surface. Infection causes inflammation of the stomach and intestines, which can lead to symptoms including stomach pains, nausea, vomiting and diarrhea.
In PyeongChang, there have already been 199 confirmed cases of norovirus — many of those sickened have been security guards hired for the games. Due to severe gastrointestinal symptoms, 41 guards have been hospitalized and more than 1,200 were placed in quarantine. …