A cancer-treating technique being studied at the University of Pennsylvania has had dramatic results for some of the patients involved. Thanks to an experimental leukemia treatment the team first tried last year, 7-year-old Emma Whitehead is now in remission, the scientists have reported at a meeting of the American Society of Hematology this week. She is one of a dozen patients that have undergone the treatment; a third of those patients are now cancer-free.
Hemophilia, a disease whose victims can suffer serious internal bleeding and may bleed to death from injuries, has a long and eventful history. Caused by defective blood clotting factors, the disease has been with us since at least the second century, when a rabbi gave mothers whose first two sons had bled to death from circumcision wounds permission to leave the third sons uncircumcised. It also famously afflicted several members of European royal families. But a study published in the New England Journal of Medicine brings us a bit closer to a new kind of historic event: a cure.
Vaccines usually work by getting the body to make antibodies against a virus, so when the virus appears on the scene, the immune system is prepared to tag it for destruction. But getting the body excited about making such antibodies isn’t always easy. It’s this stumbling block that has made HIV vaccines so disappointing so far, and in response, some scientists have reached for the big guns of biology. In a paper published today in Nature, one team reports that they’ve been able to make mice immune to HIV using, of all things, gene therapy.
Best known as a process for replacing faulty genes with fresh ones to treat chronic diseases, gene therapy seems, at first glance, like overkill. It involves engineering a lab-grown virus to permanently insert a gene into a patient’s genome, and it can be dicey, to say the least. Despite two decades of research, no gene therapy treatments have made it out of clinical trials. But given the difficulty of getting the immune system to buckle down and make antibodies against HIV on its own, using gene therapy starts to make a kind of sense. Read More
What’s the News: After a bone marrow transplant cured a Berlin man of HIV in 2008, scientists have been working to see whether similar, though less drastic, measures could be a treatment for the disease. And judging from the results of a recent clinical trial that used gene therapy to accomplish the goal, there’s potential.
What’s the Context:
Biologist George Church, examining a molecular model.
George Church, the geneticist behind the Personal Genome Project, is envisioning a package deal: get your genome sequenced, and he and his collaborators will develop a line of induced pluripotent stem cells (IPS) from your tissue, so in the future, you’ll be able upgrade your system with organs and tissues bearing both your genes and special extras like genes from centenarians. It’s combining stem cells with gene therapy. In an interview with Church, David Ewing Duncan over at Technology Review asks him to elaborate. Why does he think this science fiction scenario is in our near future?
What’s the News: Medicine in the age of genes overflows with daring new techniques and treatments, from personalized chemotherapy to prenatal genetic testing, each heralded as a game-changer. But rarely do we get an assessment of a treatment’s long-term good, which is why recent papers following up on one of the most controversial genetic treatments, gene therapy, are making waves: though one patient developed leukemia from the treatment, 13 of 16 kids treated with gene therapy for a severe immune disorder at least 9 years ago have been cured, adding to the sense that the field is on its way to recovery from early setbacks.
Modified immune cells decimated chronic lymphocytic leukemia, scientists found.
What’s the News: Striking results in a very small study have got the web a-buzz about a new cancer treatment: With three leukemia patients at the ends of their ropes, scientists modified some of their immune cells with a gene that enabled them to hunt down cancer cells. Remarkably, the treatment wiped out more than two pounds of tumor tissue in each patient, and the three have now been in remission for a year.
But what weight does such a small study carry, what about the side effects, and what do these results mean for people with other cancers?
What’s the News: Hemophilia is perhaps best known as a disease of nineteenth-century royalty (specifically, of the oft-intermarried Hapsburgs), but it has evaded our efforts at a cure for thousands of years. And its effects are gruesome: mutations in the gene for a crucial clotting factor mean that victims can rapidly bleed to death from even small cuts.
Now, researchers working with hemophiliac mice have demonstrated a simple and apparently safe technique to swap in a functioning gene, giving hope for a future respite for sufferers of the disease.
Back in the 1980s, gene therapy was one of science’s greatest hopes and hypes, and researchers predicted the technique would be used to cure a huge range of illnesses. During the 90s, many early gene therapy trials were effective or downright dangerous, some causing cancer or even death. But more recently, scientists who stuck with gene therapy have started to see positive results, with promising treatments for malformed hemoglobin, color blindness, and depression. (See the DISCOVER magazine feature “The Second Coming of Gene Therapy” for more.) Now, researchers have announced that they’ve successfully treated the symptoms of Parkinson’s disease in a small group of people—a far cry from a cure, but still a step in the right direction.
I Once Was Blind but Now I See
The theory behind gene therapy is simple: A healthy gene hitches a ride into the patient’s genome on a virus, replacing the genes responsible for some genetic disease or disorder. Actually doing this is more difficult, because humans have a little thing called an immune system that’s remarkably efficient at finding and destroying foreign bodies. After the first U.S. death from gene therapy in 1999, and leukemia cases in France the same year, many started to think that gene therapy was more of a problem than an answer.
The early and awful failures forced all of the researchers in the field to retreat and reconsider the staggering complexity that challenged them. They could not just replace a bad gene with a good gene, as some early pundits had hoped—they also had to orchestrate the nuanced and elaborate dance between the gene products (proteins) and the patient’s immune system, which could recognize a foreign body and viciously attack it. After that was settled, gene therapists still had to find a suitable virus, or vector, to carry replacement genes into human cells without inciting a damaging or deadly immune response…. It was this new perspective more than anything else that turned gene therapy from a simple but failed and frustrated hope into, once again, medicine’s next big thing—a stunning spectacle of hubris, ignominy, and redemption on the scientific stage. [DISCOVER]
New: Gene Therapy and Parkinson’s Disease
While there’s no cure for Parkinson’s as of yet, doctors have an arsenal of methods, ranging from drugs, brain stimulation, and (now) gene therapy that help reduce the disease’s symptoms. Hopes for using gene therapy to alleviate Parkinson’s effects aren’t new. What is new is that scientists have successfully completed the first randomized, controlled, double-blind trial of treating Parkison’s patients with gene therapy—and they found that it significantly improved debilitating symptoms such as tremors, motor skill problems, and rigidity. Read More
Earlier this week at a scientific conference in Boston, HIV researchers announced a remarkable success in countering the virus’ drain on the immune system. But this early step is far from a cure.
Why it’s exciting:
Carl June and colleagues tested six male patients who already had HIV and were taking a standard antiviral regimen. Like many HIV patients, the drugs helped them, but their counts of immune cells stayed low. June’s team tested a therapy created by Sangamo BioSciences in Richmond, California, that alters a patient’s actual white blood cells to make them more HIV-resistant.
Researchers removed a sample of CD4+ T cells, the type of immune cells affected by HIV, from each man and used Sangamo’s enzyme to disrupt the CCR5 gene, which encodes a protein that HIV uses to enter CD4+ cells. The engineered cells were then infused back into the patients. Immune-cell counts subsequently rose for five of the six patients who received the therapy. “It’s very exciting,” says John Rossi, a molecular biologist at the City of Hope’s Beckman Research Institute in Duarte, California. “If they did this several times in a given patient, you could establish a high percentage of resistant cells.” [Nature]
The idea came from the “Berlin Patient,” who we’ve written about before at 80beats. He became famous after receiving a donation of bone marrow from someone who carried a mutation in CCR5 that made them resistant to HIV.