Stories about: Drug discovery

Six emerging trends in vaccine development

boy receiving vaccine-shutterstock

Vaccines to protect against infectious disease are the single most effective medical product, but developing new ones is a challenging and lengthy process, limiting their use in developing countries where they are most needed. Once a new vaccine is developed, it undergoes animal testing, which is time-consuming and does not necessarily reflect human immunity.

“It can take decades from the start of vaccine development to FDA approval at huge cost,” says Ofer Levy, MD, PhD, a physician and researcher in the Division of Infectious Diseases at Boston Children’s Hospital. “We are working on making the process faster and more affordable.”

A variety of new strategies are emerging to facilitate vaccine development and delivery:

1. Modular approaches to vaccine production

The Multiple Antigen Presenting System (MAPS) is one innovative modular method to more efficiently produce vaccines that provide robust immunity.

Read Full Story | Leave a Comment

New Human Neuron Core to analyze ‘disease in a dish’

Human Neuron CoreLast week was a good week for neuroscience. Boston Children’s Hospital received nearly $2.2 million from the Massachusetts Life Sciences Center (MLSC) to create a Human Neuron Core. The facility will allow researchers at Boston Children’s and beyond to study neurodevelopmental, psychiatric and neurological disorders directly in living, functioning neurons made from patients with these disorders.

“Nobody’s tried to make human neurons available in a core facility like this before,” says Robin Kleiman, PhD, Director of Preclinical Research for Boston Children’s Translational Neuroscience Center (TNC), who will oversee the Core along with neurologist and TNC director Mustafa Sahin, MD, PhD, and Clifford Woolf, PhD, of Boston Children’s F.M. Kirby Neurobiology Center. “Neurons are really complicated, and there are many different subtypes. Coming up with standard operating procedures for making each type of neuron reproducibly is labor-intensive and expensive.”

Patient-derived neurons are ideal for modeling disease and for preclinical screening of potential drug candidates, including existing, FDA-approved drugs. Created from induced pluripotent stem cells (iPSCs) made from a small skin sample, the lab-created human neurons capture disease physiology at the cellular level in a way that neurons from rats or mice cannot.

Read Full Story | Leave a Comment

Five new developments in hemophilia

Ellis Neufeld hemophiliaEllis Neufeld, MD, PhD, is a hematologist at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center.

From new longer-acting drugs to promising gene therapy trials, much is changing in the treatment of hemophilia, the inherited bleeding disorder in which the blood does not clot. Hemophilia Awareness Month comes at a time of both progress and remaining challenges.

1. Many more treatment products are being introduced, including some that last longer.

People with hemophilia lack or have defects in a “factor”—a blood protein that helps normal clots form. Of the approximately 20,000 people with hemophilia in the U.S., about 80 percent have hemophilia A, caused by an abnormally low level of factor VIII, and most of the rest have hemophilia B, caused by abnormally low levels of factor IX. Many patients with severe hemophilia give themselves prophylactic IV infusions of the missing factor to prevent bleeding (which otherwise can lead to crippling joint disease when blood seeps into the joint and enzymes released from blood cells erode the cartilage).

Hemophilia factors traditionally have such a short half-life that we tend to treat patients every other day with factor VIII and twice a week with factor IX. The first two longer-lasting products came onto the market within the past year, and more are on the way. So now, with factor IX, it is possible to get an infusion just once a week and not bleed. This is really changing how we think about the disease. So far, the longer-acting factor VIII products are not yet long-lasting enough to make as dramatic a difference in the frequency of infusions. And creating really long-acting factors remains a challenge.

Read Full Story | Leave a Comment

Can rare disease genes be protective?

Carriers of the rare disease Niemann-Pick C1 may be protected against Ebola.
Carriers of the rare disease Niemann-Pick C1 may be protected against Ebola.
First of several posts to commemorate (Feb 28, 2015).

Evolution is a strange thing: sometimes it favors keeping a mutation in the gene pool, even when a double dose of it is harmful—even fatal. Why? Because a single copy of that mutation is protective in certain situations.

A classic example is the sickle-cell mutation: People carrying a single copy don’t develop sickle cell disease, but they make enough sickled red blood cells to keep the malaria parasite from getting a toe-hold. (Certain other genetic disorders affecting red blood cells have a similar effect.)

Or consider cystic fibrosis. Carriers of mutations in the CFTR gene—some 1 in 25 people of European ancestry—appear to be protected from typhoid fever, cholera and possibly tuberculosis.

Read Full Story | Leave a Comment

A link between cystic fibrosis and arsenic poisoning?

boys playing in arsenic-endemic area of Bangladesh

Since its causative gene was sequenced in the 1980s, cystic fibrosis (CF) has been the “textbook” genetic disease. Several thousand mutations have been identified in the CFTR protein, which regulates the flow of chloride in and out of cells. When CFTR is lost or abnormal, thick mucus builds up, impairing patients’ lungs, liver, pancreas, and digestive and reproductive systems, and making their lungs prone to opportunistic infections.

But new research could add a chapter to the textbook, pinpointing an unexpected environmental cause of CF-like illness. A study reported in the February 5 New England Journal of Medicine found that people with arsenic poisoning have high chloride levels in their sweat—the classic diagnostic sign of CF.

Read Full Story | Leave a Comment

Advancing clinical trials for Niemann-Pick type C: Sweet news for cyclodextrin

cyclodextrin Febreze Niemann-Pick type cOlaf Bodamer, MD, PhD, is associate chief of the Division of Genetics and Genomics at Boston Children’s Hospital and is launching a multidisciplinary clinic this spring for lysosomal storage diseases—including Niemann-Pick type C, sometimes referred to as “childhood Alzheimer’s.”

Niemann-Pick disease type C (NP-C) has come a long way since its first description as an entity in the 1960s. Part of a group of rare metabolic disorders known as lysosomal storage diseases, NP-C leaves children unable to break down cholesterol and other lipid molecules. These molecules accumulate in the liver, spleen and brain, causing progressive neurologic deterioration.

I still vividly remember when I diagnosed my first patient with this devastating disease, a 3-year-old boy who had global developmental delay, restricted eye movement, loss of motor coordination and loss of speech. I spent hours with the family, explaining what was known about NP-C. When faced with the question about treatability and outcome, I could barely find the right words, but had to acknowledge that the outcome was inevitably fatal and that there was no specific treatment other than supportive measures to treat his symptoms.

Read Full Story | Leave a Comment

Live imaging captures how blood stem cells take root in the body

For years, the lab of Leonard Zon, MD, director of the Stem Cell Research Program at Boston Children’s Hospital, has sought ways to enhance bone marrow transplants for patients with cancer, serious immune deficiencies and blood disorders. Using zebrafish as a drug-screening platform, the lab has found a number of promising compounds, including one called ProHema that is now in clinical trials.

But truthfully, until now, Zon and his colleagues have largely been flying blind.

“Stem cell and bone marrow transplants are still very much a black box: cells are introduced into a patient and later on we can measure recovery of their blood system, but what happens in between can’t be seen,” says Owen Tamplin, PhD, in the Zon Lab. “Now we have a system where we can actually watch that middle step.”

Read Full Story | Leave a Comment

Is pediatric cancer research entering a “post-genomic” period?

Epigenome_shutterstock_52453933_resize

“Genome” has been the biggest word in cancer research in the last decade. Thanks largely to the high throughput and relatively low cost of “next generation” DNA-sequencing technologies, researchers have screened thousands of tumors for gene mutations that could explain their malignant properties and reveal possible treatment targets.

Sequencing of adult tumors has revealed a broad spectrum of cancer-causing gene mutations. Childhood tumors, by contrast, have turned out to be relatively simple from a genomic point of view. By and large, they harbor few mutations in genes that code for relatively “druggable” targets with discrete effects, like kinases.

“Pediatric tumors are very ‘pure,’ with very low mutation rates,” says Carlos Rodriguez-Galindo, MD, director of the Solid Tumor Center at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. “To really understand the nature of pediatric cancer, we need to turn to epigenetics and gene regulation.”

Rodriguez-Galindo is not alone in this view. There is a trend afoot in pediatric cancer research: the study of gene regulation and epigenetics is beginning to overshadow classic tumor genetics and genomics.

Read Full Story | Leave a Comment

Overturning dogma to open the black box of DIPG

pons DIPG brain tumor brainstem glioma

You can’t advance the care of a disease that you can’t study. And for 40 years, that was the case with a rare, uniformly fatal pediatric brain tumor called diffuse intrinsic pontine glioma, or DIPG.

DIPG isn’t like most brain tumors. Rather than forming a solid mass, it weaves itself among the nerve fibers of the pons—a structure in the brain stem that controls vital functions like breathing, blood pressure and heart rate—making it impossible to biopsy. At least, that’s been the dogma.

“DIPG is the only tumor that historically has not been biopsied, because it’s found in such a critical place in the brain,” says Mark Kieran, MD, PhD, director of the Brain Tumor Center at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. “In the 1970s and ‘80s, children with DIPG who underwent biopsy had multiple neurologic complications, so the dogma became ‘no biopsies.'”

As a result, research was stalled by a lack of available tumor tissue to study. To address this, Kieran and his colleagues Nalin Gupta, MD, and Michael Prados, MD, PhD, of the University of California, San Francisco, launched a new clinical trial of DIPG in 2012. The trial is leveraging advances in microsurgery and genomics to give researchers their first peek into the molecular nature of DIPGs.

Read Full Story | 3 Comments | Leave a Comment

15 health care predictions for 2015

Crystal ball fortuneteller-Shutterstock-cropped
2014 continued to see massive evolution in health care—from digital health innovations to the maturation of technologies in genomics, genome editing and regenerative medicine to the configuration of the health care system itself. We asked leaders from the clinical, research and business corners of Boston Children’s Hospital to weigh in with their forecasts for 2015. Click “Full story” for them all, or jump to:
The consumer movement in health care
Evolving care models
Genomics in medicine
Stem cell therapeutics
Therapeutic development
New technology
Biomedical research

Read Full Story | Leave a Comment