“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.”
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.
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.
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 Globereported over the weekend that while researchers at the University of California at Berkeley first developed CRISPR, the technique is booming in labs around Boston.
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.
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.
Technology sometimes unfolds at a slow, measured pace and sometimes at lightning speed. Right now, we are witnessing what is arguably one of the fastest moving fields in biomedical science: a form of genome editing aptly known as CRISPR.
CRISPR allows researchers to make very precise—some would say crisp—changes to the genomes of human cells and those of other organisms. You might think of it as a kind of guided missile. Its precision is opening the doors to a wide variety of research and, hopefully, medical applications. Indeed, the possibilities seem to be bound only by scientists’ imaginations.
“For a long time, we have been accumulating new knowledge about which gene mutation causes which disease. But until very recently, we haven’t had the ability to go in and correct those mutations,” explains Feng Zhang, PhD, a core member of the Broad Institute of Harvard and MIT, and one of the method’s pioneers. “CRISPR is one of the tools that is starting to allow us to directly go in and do surgery on the genome and replace the mutations.”
CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. While this name is a bit verbose, it points to the technology’s origins: a set of genetic sequences first discovered in bacteria.
Seeing that his mother, Kadriye, wasn’t looking, Emir Seyrek got an impish grin on his face, the kind only a two-year-old can have. He quietly dumped his bowl of dry cereal out on his bed and, with another quick look towards his mother, proceeded to pulverize the flakes to dust with his toy truck. The rest of the room burst out laughing while his mother scolded him. Despite the scolding, though, the impish grin remained.