Stories about: gene therapy

Forty years waiting for a cure: ALD gene therapy trial shows early promise

Ethan and me, June 1977
Ethan and me, June 1977

A small piece of notepaper, folded twice, sits tucked in a slot of the secretary desk in the living room. Every so often, I pull it out, read it, then reread.

Addressed to my mom, the paper has a question and two boxes, one “yes” and one “no,” written with the careful precision of a 7-year-old.

I am sad of Ethan. You too?

A check marks the box.

Yes. Yes, I am sad too.

Learning about adrenoleukodystrophy

My brother Ethan Williams was 9 years old in the fall of 1976, when he began to lose his sight. For my parents, that winter brought an endless round of doctor visits, therapists and lab tests.

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Drug ‘cocktail’ could restore vision in optic nerve injury

regenerating optic nerves cropped
Gene therapy achieved extensive optic nerve regeneration, as shown in white, but adding a potassium channel blocking drug was the step needed to restore visual function. In the future, it might be possible to skip gene therapy and inject growth factors directly. (Fengfeng Bei, PhD, Boston Children’s Hospital)

When Zhigang He, PhD, started a lab at Boston Children’s Hospital 15 years ago, he hoped to find a way to regenerate nerve fibers in people with spinal cord injury. As a proxy, he studied optic nerve injury, which causes blindness in glaucoma — a condition affecting more than four million Americans — and sometimes in head trauma.

By experimenting with different growth-promoting genes and blocking natural growth inhibitors, he was able to get optic nerve fibers, or axons, to grow to greater and greater lengths in mice. But what about vision? Could the animals see?

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Storify: The science and business of cystic fibrosis

Cystic Fibrosis panelWhat happens when you put a doctor who specializes in cystic fibrosis in the same room as two biotech executives, one of whom is a ‘dadvocate’ of a teenager with CF? View the highlights and reactions to a a dynamic panel discussion at the Boston Children’s Hospital Global Pediatric Innovation Summit + Awards with Gregory Sawicki, MD, MPH, director of the Boston Children’s Cystic Fibrosis Center; David Meeker, MD, Genzyme president and CEO; Bob Coughlin, Massachusetts Biotechnology Council president and CEO; and moderator Luke Timmerman, founder and editor of The Timmerman Report.

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So far, so good for gene therapy patient Emir Seyrek

Emir Seyrek gene therapy Wiskott-Aldrich ThrivingRemember Emir Seyrek, the Turkish boy who last year was the first patient in gene therapy trial for a genetic immunodeficiency called Wiskott-Aldrich Syndrome? Emir traveled back to the U.S. earlier this month for an annual follow-up visit with his care team at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. The news was quite good.

“Emir is the star of the trial,” Sung-Yun Pai, MD—a Dana-Farber/Boston Children’s gene therapy and immunodeficiency transplant specialist and lead (along with David Williams, MD, and Luigi Notarangelo, MD) of the U.S. arm of the trial—tells our sister blog, Thriving. “He has the highest platelet count of all of the children who have gone through gene therapy with this vector so far. His immune function is excellent, and we have no worries whatsoever from a bleeding standpoint. He’s perfectly safe to play like a normal child.”

Learn more about Emir’s progress on Thriving.

 

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Gene therapy restores hearing in deaf mice

A closeup of the sensory hair bundles in the cochlea (inverted v's), each containing 50 to 100 microvilli tipped with TMC proteins. Cell bodies are below the bundles. (Gwenaelle S. Geleoc & Artur A. Indzhykulian)
The inverted V’s above are sensory hair bundles in the ear, each containing 50 to 100 microvilli tipped with TMC proteins. Gene therapy restores hearing by providing working copies of those proteins. (Gwenaelle Geleoc & Artur Indzhykulian)

More than 70 different genes are known to cause deafness when mutated. Jeffrey Holt, PhD, envisions a day when patients with hearing loss have their genome sequenced and their hearing restored by gene therapy. A proof-of-principle study published today by the journal Science Translational Medicine takes a clear step in that direction, restoring hearing in deaf mice.

“Our gene therapy protocol is not yet ready for clinical trials—we need to tweak it a bit more—but in the not-too-distant future we think it could be developed for therapeutic use in humans,” says Holt, a scientist in the F.M. Kirby Neurobiology Center at Boston Children’s Hospital and an associate professor of Otolaryngology at Harvard Medical School.

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Advances in SCID (“bubble boy” disease): A Q&A with a child hematologist/oncologist

David Williams, Luigi Notarangelo and Sun-Yung PaiSung-Yun Pai, MD, a pediatric hematologist/oncologist at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, was lead author on two recent articles on severe combined immune deficiency (SCID) in The New England Journal of Medicine. The first reviewed outcomes after bone marrow transplantation; the second reported the first results of a new international gene therapy trial for X-linked SCID. Here, she discusses what’s known to date about these therapies.

Q: What is SCID?

A: SCID is a group of disorders that compromise the blood’s T cells, a key component of the immune system that helps the body fight common viral infections, other opportunistic infections and fungal infections. T-cells are also important for the development of antibody responses to bacteria and other microorganisms. A baby born with SCID appears healthy at birth, but once the maternal antibodies that the baby is born with start to wane, the infant is at risk for life-threatening infections. Unless diagnosed and treated—with a stem cell transplant from a healthy donor or a more experimental therapy like gene therapy—babies with SCID typically die before their first birthday.

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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.

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CRISPR gene editing is creating a buzz in Boston

CRISPR gene editing Boston

You have an immune system. Your cat has an immune system. And bacteria have an immune system, too—one that we’ve tapped to make one of the most powerful tools ever for editing genes.

The tool is called CRISPR (for “clustered regularly interspaced short palindromic repeats”), and it makes use of enzymes that “remember” viral genes and cut them out of bacterial genomes. Applied to bioengineering, CRISPR is launching a revolution. And the Boston Globe reported over the weekend that while researchers at the University of California at Berkeley first developed CRISPR, the technique is booming in labs around Boston.

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A first for CRISPR: Cutting genes in blood stem cells

CRISPR T-cells stem cells HIV gene editing
The CRISPR system (red) at work.

CRISPR—a gene editing technology that lets researchers make precise mutations, deletions and even replacements in genomic DNA—is all the rage among genomic researchers right now. First discovered as a kind of genomic immune memory in bacteria, labs around the world are trying to leverage the technology for diseases ranging from malaria to sickle cell disease to Duchenne muscular dystrophy.

In a paper published yesterday in Cell Stem Cell, a team led by Derrick Rossi, PhD, of Boston Children’s Hospital, and Chad Cowan, PhD, of Massachusetts General Hospital, report a first for CRISPR: efficiently and precisely editing clinically relevant genes out of cells collected directly from people. Specifically, they applied CRISPR to human hematopoietic stem and progenitor cells (HSPCs) and T-cells.

“CRISPR has been used a lot for almost two years, and report after report note high efficacy in various cell lines. Nobody had yet reported on the efficacy or utility of CRISPR in primary blood stem cells,” says Rossi, whose lab is in the hospital’s Program in Cellular and Molecular Medicine. “But most researchers would agree that blood will be the first tissue targeted for gene editing-based therapies. You can take blood or stem cells out of a patient, edit them and transplant them back.”

The study also gave the team an opportunity to see just how accurate CRISPR’s cuts are. Their conclusion: It may be closer to being clinic-ready than we thought.

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A double-shot of good news for SCID: Promising transplant and gene therapy data

Hematopoietic hierarchy aging blood cell hematopoietic stem cell blood disorder Derrick Rossi
Blood-forming hematopoietic stem cells (top) give rise to all blood and immune cell types. In children with SCID, the steps leading to immune cells are broken.

In the world of fatal congenital immunodeficiency diseases, good news is always welcome, because most patients die before their first birthday if not treated. Babies with severe combined immunodeficiency disease, aka SCID or the “bubble boy disease,” now have more hope for survival thanks to two pieces of good news.

Transplants are looking up

First came a July paper in the New England Journal of Medicine (NEJM) by the Primary Immune Deficiency Treatment Consortium. This North American collaborative analyzed a decade’s worth of outcomes of hematopoietic stem cell transplant (HSCT), currently the only standard treatment option for SCID that has a chance of providing a permanent cure.

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