Stories about: Drug discovery

Solving puzzles with Cigall Kadoch

Cigali Kadoch-Rubiks cube-croppedGrowing up in the San Francisco area, Cigall Kadoch, PhD, had a passion for puzzles. The daughter of a Moroccan-born, Israeli-raised father and a mother from Michigan who together developed an interior design business, Kadoch excelled in school and pretty much everything else. Above all, she loved to solve brain-teasers.

For Kadoch, the Rubik’s cube represents a love of puzzles, as well as the structure of the protein complexes she studies in her research at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. Dana-Farber Chief of Staff Stephen Sallan, MD, describes her as “addicted to discovery.”

In high school, however, Kadoch came up against a problem that defied solution. Breast cancer took the life of a beloved family caretaker who had nurtured her interests in science and nature. She knew little about cancer except that it took lives far too early.

“I was deeply saddened and very frustrated at my lack of understanding of what had happened,” recalls Kadoch. “I thought to myself, cancer is a puzzle that isn’t solved, let alone even well-defined, and I want to try. As naïve a statement as that was, it was a defining moment—one which I never could have predicted would actually shape my life’s efforts.”

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Supercharged marrow transplant: Zebrafish reveal drugs that aid engraftment

Zebrafish stem cell engraftment bone marrow
(Jonathan Henninger and Vera Binder)

Bone marrow transplantation, a.k.a. stem cell transplantation, can offer a cure for certain cancers, blood disorders, immune deficiencies and even metabolic disorders. But it’s a highly toxic procedure, especially when a closely matched marrow donor can’t be found. Using stem cells from umbilical cord blood banked after childbirth could open up many more matching possibilities, making transplantation safer.

Except for one problem. “Ninety percent of cord blood units can’t be used because they’re too small,” says Leonard Zon, MD, who directs the Stem Cell Research Program at Boston Children’s.

But what if the blood stem cells in those units could be supercharged to engraft more efficiently in the bone marrow and grow their numbers faster? That’s been the quest of the Zon lab for the past seven years, in partnership with a see-through zebrafish called Casper.

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Daniel Kohane, MD, PhD, at TEDMED: “Smart vehicles for safer medications”

“The drugs that I take don’t just go to the places in my body they’re supposed to go to do the things they do. They actually go everywhere. And what they do in those other places can be whatever.”

With those words, Daniel Kohane, MD, PhD—director of the Laboratory for Biomaterials and Drug Delivery at Boston Children’s Hospital—launched into a TEDMED talk about technologies that get drugs to where they need to go with much greater precision, like:

“Progress in this field is limited only by the imagination of the investigators and, to some degree, by reality,” says Kohane, who also sees patients in Boston Children’s Department of Critical Care Medicine. “You can achieve really big things by thinking really small.”

Click the image above to watch his whole talk.

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Breaking the allergic asthma cycle…by targeting nerve endings

asthma therapeuticsExisting asthma medications work by suppressing inflammatory signaling by immune cells or by dilating constricted airways. Over time, though, these drugs’ benefits can wane. New research supports a surprising new tactic for controlling asthma: targeting sensory nerve endings in the lungs with a selective drug.

Our lungs are known to contain specialized sensory neurons known as nociceptors that connect to the brainstem. Best known for causing the perception of pain, nocieptors also trigger the cough reflex in the lungs when they detect potential harms like dust particles, chemical irritants or allergens. Nociceptor nerve endings are known to be more plentiful and more readily activated in people with asthma. Now it’s also clear that they help drive allergic inflammation.

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Targeting inflammation in sickle cell disease with fatty acids

sickle cell disease red blood cells
(OpenStax College/Wikimedia Commons)

Painful, tissue-damaging vaso-occlusive crises (a.k.a. pain crises) are one of the key clinical concerns in sickle cell disease (SCD). The characteristic C-shaped red blood cells of SCD become jammed in capillaries, starving tissues of oxygen and triggering searing pain. Over a patient’s life, these repeated rounds of oxygen deprivation (ischemia) can take a heavy toll on multiple organs.

There’s some debate as to why these crises take place—is the sickled cell’s shape and rigidity at fault, or are the blood vessels chronically inflamed and more prone to blockage? Either way, doctors can currently do little to treat vaso-occlusive crises, and nothing to prevent them.

The inflammation view, however, is leading some researchers to ask whether omega-3 fatty acids—which can alleviate inflammation—might be part of the solution. A recent mouse study in the journal Haematologica, led by Mark Puder, MD, PhD, of Boston Children’s Vascular Biology Program, and Carlo Brugnara, MD, of the hospital’s Department of Laboratory Medicine reveals some molecular clues and suggests that human trials of omega-3s might be a good next step.

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Treating chronic pain: From humans to mice and back

"Reverse engineering" reveals the enzyme sepiapterin reductase (SPR)—the large gray molecule in the background—as a new target for pain treatment. This take on Michelangelo's famous Sistine Chapel image symbolizes the link between human pain patients and the mouse model. The lab-designed SPR inhibitor (in green), shown within SPR’s active pocket, is the "bridge" between the two species. (Image: Alban Latremoliere)
“Reverse engineering” reveals the enzyme sepiapterin reductase (SPR)—the large gray molecule in the background—as a new target for pain treatment. This take on Michelangelo’s famous Sistine Chapel image symbolizes the link between human pain patients and the mouse model. The lab-designed SPR inhibitor in green, shown within SPR’s active pocket, is the “bridge” between the two species. (Image: Alban Latremoliere)

Non-narcotic treatments for chronic pain that work well in people, not just mice, are sorely needed. Drawing from human pain genetics, an international team demonstrates a way to break the cycle of pain hypersensitivity without the development of addiction, tolerance or side effects. Their findings were published online today in the journal Neuron.

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Souped-up fish facility boosts drug discovery and testing

closeup of zebrafish-20150526_ZebraFishCeremony-60The care and feeding of more than 250,000 zebrafish just got better, thanks to a $4 million grant from the Massachusetts Life Sciences Center to upgrade Boston Children’s Hospital’s Karp Aquatics Facility. Aside from the fish, patients with cancer, blood diseases and more stand to benefit.

From a new crop of Boston-Children’s-patented spawning tanks to a robotic feeding system, the upgrade will help raise the large numbers of the striped tropical fish needed to rapidly identify and screen potential new therapeutics. It’s all part of the Children’s Center for Cell Therapy, established in 2013. We put on shoe covers and took a look behind the scenes. (Photos: Katherine Cohen)

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What we’ve been reading: Week of May 18, 2015

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From cancer to feet: the power of Twitter in healthcare (MedCity News)
Why does Twitter care about the healthcare industry? Craig Hashi, one of two Twitter engineers dedicated to healthcare, details the opportunities.

MIT’s implantable device could help docs determine best cancer medicine (Boston Business Journal)
Removing the trial and error associated with cancer drug treatments is high on oncologists’ wish lists. Heeding that call, MIT has developed an implantable device (about the size of a grain of rice) that can carry up to 30 different drug doses to a cancerous tumor, and then be removed to test responses.

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First six months of life are best for stimulating child heart growth

heart-regeneration-study2
In these sample sections of mouse heart, the color blue signifies scar tissue. Damage from scarring was minimized by early administration of the drug neuregulin.

Developing a child-centric approach to treating heart failure is no easy task. For one thing, the underlying causes of decreased cardiac function in children vastly differ from those in adults. While most adults with heart failure have suffered a heart attack, heart failure in children is more likely the result of congenital heart disease (CHD), or a structural defect present at birth that impairs heart function. And most therapies designed for adults haven’t proven equally effective in children.

Stimulating heart muscle cells to regenerate is one way cardiac researchers at Boston Children’s Hospital’s Translational Research Center hope to restore function to children’s ailing hearts. In this area, children actually have an advantage over adults: their young heart cells are better suited for regrowth.

Reporting in the April 1 Science Translational Medicine, Brian Polizzotti, PhD, and Bernhard Kuhn, MD, demonstrate that not only does the drug neuregulin trigger heart cell regeneration and improve overall heart function in newborn mice, but its effects are most potent for humans within the first six months of life.

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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.

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