Researchers may have taken a step towards curing the rare, inherited brain disease made famous by the movie Lorenzo’s Oil–and also towards ushering a new era of gene therapy. To help two young boys suffering from the disease, researchers tried an experimental treatment using a deactivated version of the HIV virus. The virus delivered working copies of a gene to stem cells from the patients’ bone marrows. The HIV virus, stripped of genetic material that makes it toxic, integrates permanently into the DNA of cells it enters, scientists said. That means the modified gene remains in the blood-forming stem cells for the life of the patient [Bloomberg].
Adrenoleukodystrophy, or ALD, is a progressive disease characterized by the gradual destruction of the myelin sheaths that insulate neurons and nerves, allowing electrical signals to be transmitted through them. The disease is caused by a genetic defect, which prevents cells in the bone marrow from producing a crucial protein necessary for the formation of the myelin sheaths. Typically, children with ALD are given bone marrow transplants to provide them with healthy blood-forming stem cells, but in the two cases described in the study, no matching donors could be found.
In the experimental treatment, described in a paper published in Science, researchers took blood stem cells from the patients’ bone marrow and used the new vector system to genetically alter them by inserting a working copy of the … gene. The modified cells were then put back into the patients [Reuters].
(more…)
Emphysema and cystic fibrosis patients who need new lungs are faced with a life-threatening problem: more than 80 percent of donated lungs can’t be used—they’re inflamed and barely functional [Scientific American]. Transplanted lungs also fail at a much higher rate than other transplanted organs, as they’re more likely to be rejected by the recipient’s body. But a new procedure that makes use of gene therapy may soon double or triple the supply of undamaged donated lungs, and may also improve their function once transplanted.
In both pre- and post-transplant lungs, the problem is inflammation caused by insufficient amounts of an immune molecule called IL-10. Donated lungs are immediately chilled on ice, which destroys any IL-10 that may remain in the lungs, allowing substantial damage to occur before the organ can be implanted. And a lack of the molecule after transplantation increases the likelihood that inflammation will damage the organ and induce rejection [Los Angeles Times].
To get around these problems, the researchers first built a domed chamber where pig lungs were kept at body temperature with a steady flow of oxygen and nutrients moving through them. That arrangement alone prevented substantial damage to the lungs. Next, in the gene therapy stage, the researchers used a harmless virus to bring a gene that produces IL-10 into the lung cells.
(more…)
A new study may have hit upon another way to improve stem cells‘ ability to help repair damaged tissue. While stem cells can rapidly grow into any kind of new tissue, they aren’t always able to encourage new blood vessels to grow so that the tissue stays alive. But in a new study, published in the Proceedings of the National Academy of Sciences, scientists describe a way around the problem. The researchers used nanoparticles to ferry a key gene into the stem cells, which caused the cells to recruit new blood vessels, thus fueling tissue growth.
The nanoparticles carried a gene (VEGF) that is known to stimulate new blood vessel growth. When the modified cells were injected into mice whose hind limbs had been injured, the tissue that regrew to repair the damage had three times the blood vessel density of similar tissue in mice given unmodified cells. Four weeks later, only 20 per cent of the mice given modified cells had lost limbs, compared with 60 per cent in mice that received unmodified cells [New Scientist].
(more…)
For two squirrel monkeys nicknamed Dalton and Sam, life has gotten a lot more colorful. Researchers used gene therapy to correct the color blindness of the two adult monkeys, giving them the ability to distinguish between red and green for the first time. The fascinating accomplishment suggests that scientists may someday be able to cure other kinds of blindness in humans. And because the treated monkeys were “middle aged”, it challenges the assumption that gene therapies cannot work in adults because their brain connections are too set in their ways to change beneficially [New Scientist].
The field of gene therapy, in which a malfunctioning gene in a patient’s body is replaced with a functional one, fell into disarray one decade ago following the death of an 18-year-old in a clinical trial. But since then scientists have regrouped, using animal studies to probe the technique’s safety. Last year, researchers progressed to the point of safety trials in humans for the treatment of one rare eye condition called Leber congenital amaurosis, and were able to dramatically improve the patients’ sight. Those results were stunning, but they were also achieved in children, whose still-growing brains can rewire themselves on the fly in response to new sources of visual stimuli [Wired.com].
In the new study, published in Nature, the researchers used a type of squirrel monkey in which the males lack a visual pigment called L-opsin. Its absence renders the monkeys color-blind, unable to distinguish reds and green. Most of the females, on the other hand, see in full color. So the scientists got to wondering: what would happen if they gave a boy squirrel monkey the same opsin that girls have [Scientific American]. They used a harmless virus to ferry in the gene that makes opsin, injecting the virus behind the monkeys’ retinas.
(more…)
In a remarkable announcement, German researchers have declared that they “functionally cured” a patient of AIDS, eradicating all traces of the virus from his body. The feat was accomplished with a bone marrow transplant from a donor who had a genetic resistance to the virus, and researchers say that 20 months later they can find no trace of the virus in the patient’s blood, bone marrow, or organ tissue.
But the accomplishment shouldn’t be taken as a sign that a cure for the 33 million people living with AIDS is around the corner, researchers are hasty to add. Professor Rodolf Tauber from the [German] clinic said: “This is an interesting case for research. But to promise to millions of people infected with HIV that there is hope of a cure would not be right” [BBC News]. Reasons for this caution include the small number of potential donors with the HIV-resistant mutation, and the difficulty and expense of bone marrow transplants.
(more…)
In a promising result for gene therapy, researchers have dramatically improved the vision of several patients with a rare, inherited eye condition called Leber congenital amaurosis. The early study was intended to simply test the safety of the treatment, but the patients displayed such significant improvement that researchers decided to publicize the results.
Gene therapy works on a simple principle – to replace a malfunctioning gene, and restore function to a part of the body affected by a genetic disorder. In practice, however, it has proved very difficult to find ways to introduce the new gene copies in the correct tissues, and experiments in animals have had mixed results [BBC News].
(more…)
