Stories about: Leonard Zon

Zebrafish plus iPS cells make a drug discovery platform with muscle

Cell cover about using zebrafish and iPS cells to find muscle-building drugs.
In a one-two-three punch, a rapid screen in zebrafish can quickly identify a short list of drug candidates to test in mice and in patient-derived cells.

Scientists have had little success in growing skeletal muscle for patients with muscular dystrophy and other disorders that degrade and weaken muscle. Undertaking experiments in zebrafish, mouse and human cells, researchers have identified a way to do that, creating cells that Leonard Zon, MD, hopes to see tested in patients in the next several years.

But what really excites Zon, director of the Stem Cell research program at Boston Children’s Hospital, is the power of the chemical screening platform he and his colleagues used. Described last week in the journal Cell, it found a cocktail of three compounds that induced human muscle cells to grow—in just a matter of weeks. Zon believes it could fast-track drug discovery for multiple disorders.

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New research on blood stem cells takes root

Word cloud of words associated with hematopoietic stem cells and blood development.
The demand for hematopoietic stem cell transplants is rising. But how can we get more cells? (Text from Bryder D, Rossi DJ and Weissman IL. Am J Pathol 2006; 169(2): 338–346.)
You need a lot of hematopoietic stem cells to carry out a hematopoietic stem cell transplant, or HSCT. But getting enough blood stem cells can be quite a challenge.

There are many HSCs in the bone marrow, but getting them out in sufficient numbers is laborious—and for the donor, can be a painful process. Small numbers of HSCs circulate within the blood stream, but not nearly enough. And while umbilical cord blood from newborn babies may present a relatively rare but promising source for HSCs, a single cord generally contains fewer cells than are necessary.

And here’s the rub: The demand for HSCs is only going to increase. Once a last resort treatment for aggressive blood cancers, HSCTs are being used for a growing list of conditions, including some solid tumor cancers, non-malignant blood disorders and even a number of metabolic disorders.

So how do we get more blood stem cells? Several laboratories at Boston Children’s Hospital and Dana-Farber/Boston Children’s Cancer and Blood Disorders Center are approaching that question from different directions. But all are converging on the same end result: making more HSCs available for patients needing HSCTs.

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Customized cell therapy for untreatable diseases: Your tax dollars at work

Leonard Zon (top) and Massachusetts Lt. Governor Timothy Murray in the Stem Cell Program's zebrafish facility. (Courtesy MLSC)
Ed. Note: Leonard Zon, MD, is founder and director of the Boston Children’s Hospital Stem Cell Program, which yesterday was awarded $4 million by the Massachusetts Life Sciences Center to build the Children’s Center for Cell Therapy.

As a hematologist, I see all too many children battling blood disorders that are essentially untreatable. Babies with immune deficiencies living life in a virtual bubble, hospitalized again and again for infections their bodies can’t fight. Children disabled by strokes caused by sickle cell disease, or suffering through sickle cell crises that drug treatments can’t completely prevent. Children whose only recourse is to risk a bone marrow transplant—if a suitably matched donor can even be found.

Over the past 20 years, my lab and that of George Daley, MD, PhD, at Boston Children’s Hospital have worked hard to give these children a one-time, potentially curative option—a treatment that begins with patients’ own cells and doesn’t require finding a match.

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Zebrafish make a big splash

If you look at the range of research models available to scientists today (from fungi to flies to mice and larger), one little guy stands out – a tropical freshwater fish from the rivers of Bangladesh called the zebrafish. While it may be small, this fish is having a big impact on medical science, especially in genetics, stem cell biology, and drug screening, as covered in today’s Wall Street Journal.

As we’ve mentioned previously on Vector, the zebrafish is swimming its way into many research programs, both here at Children’s Hospital Boston and across the country. As a model, they are quite attractive to researchers, in part due to their small size, their fecundity, and their surprising similarities to us (from a genetic standpoint, that is).

Richard White, who works with Leonard Zon in the Stem Cell Program at Children’s Hospital Boston, offers up an explanation for the fish’s popularity:

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From fish to people – first drug ID’d in zebrafish crosses a milestone

A recent clinical trial brings the drug FT1050 one step closer to becoming the first drug identified with the help of zebrafish (above) to make it to patients. (Soulkeeper/Wikimedia Commons)

In 2007, working with zebrafish, Leonard Zon and his team in Children’s Stem Cell Program made an unexpected discovery: That a drug originally developed to treat stomach ulcers could boost the production of blood stem cells, by about four-fold.

That drug – FT1050, a chemical variant of a fatty, hormone-like molecule called prostaglandin E2 (PGE2) – recently crossed a major milestone: the successful conclusion of a Phase I clinical trial. Led by Zon’s colleague Corey Cutler, a clinical researcher at Dana-Farber Cancer Institute, the trial aimed to determine the drug’s safety as a way of helping patients who receive umbilical cord blood stem cell transplants recover their immune function more quickly.

The trial brings the FT1050 one step closer to becoming the first drug identified with the help of zebrafish to make it to patients.

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The iSpawn: The birds, the bees, and the zebrafish

One of the characteristics that make zebrafish a fantastic model for research is that they spawn…a lot. A healthy female zebrafish can lay upwards of 1,000 eggs each week. By comparison, the mouse, another species widely used in research, may have a single 12-pup litter each month.

Sometimes, though, that isn’t enough. A researcher screening a library of chemicals for potential drugs, for instance, might need tens of thousands of zebrafish embryos, all at the same developmental stage, to have statistically meaningful results.

That researcher could really use the iSpawn.

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