Genome editing to treat hemophilia

For the first time, researchers have used a precise method of editing the genome to correct a genetic defect in live animals. In this case, researchers treated mice with hemophilia, replacing a blood clotting protein called human factor 9. After the treatment, the mice produced enough of the protein to make their blood clot normally.

The editing technology relies on proteins known as zinc fingers, which bind to specific pieces of DNA to regulate nearby genes. By engineering different zinc fingers and attaching them to a gene cutting enzyme, researchers have created precise editing tools that can snip a specific piece of the genome and insert a new gene. Researchers hope the technology will help overcome one of the major problems with existing forms of gene therapy, which allow the gene to insert itself into the genome randomly. That can disrupt important genes, in some cases causing leukemia.

According to the New York Times,

[Katherine High, a hematologist and gene therapy expert at The Children’s Hospital of Philadelphia] said it was too soon to try the technique in people, given that an adequate treatment for hemophilia already exists. She plans to test it next in dogs, which are a standard model for new hemophilia treatments. One of the possible problems with the technique is that the zinc fingers sometimes cut at sites other than the intended target site.

Patients get lab-grown blood vessels

Three dialysis patients in Poland have been successfully implanted with blood vessels grown from cultured skin cells. The engineered essels, which were about a foot long and nearly five millimeters wide, were used as shunt to provide access to the blood for dialysis. Shunts created from patients’ own vessels or synthetic materials are notoriously prone to failure, according to a release from the American Heart Association.

At follow-up exams up to eight months after implantation, none of the patients had developed an immune reaction to the implants, and the vessels withstood the high pressure and frequent needle punctures required for dialysis.

Investigators previously showed that using vessels individually created from a patient’s own skin cells reduced the rate of shunt complications 2.4-fold over a 3-year period. The availability of off-the-shelf vessels could avoid the expense and months-long process involved in creating custom vessels for each patient, making the technique feasible for widespread use.

The blood vessels, which are made by Cytograft Tissue Engineering, could provide a cheaper alternative to those made from a patient’s own cells. “This version, built from a master donor, is available off the shelf and at a dramatically reduced cost,” estimated at $6,000 to $10,000, Cytograft Chief Executive Todd McAllister told the Associated Press. The grafts also have the potential to be used in lower limb bypass to route blood around diseased arteries, to repair congenital heart defects in pediatric patients, and to fix damaged arteries in soldiers, who might otherwise lose a limb, said McAllister.

A TB vaccine improves type 1 diabetes.

A small clinical trial of people with severe type 1 diabetes shows that bacillus Calmette-Guerin (BCG), a generic drug developed as a vaccine against tuberculosis, can reverse the disease, at least temporarily.

“We found that even low doses of BCG could transiently reverse type 1 diabetes in human patients,” said Denise Faustman, director of the Massachusetts General Hospital Immunobiology Laboratory, in a release from the hospital. “One of the key components of this study was our development of a way to measure the death of the autoreactive T cells that destroy the ability of the pancreas to produce insulin. Not only did we observe and measure the death of these self-targeting immune cells, but we also saw evidence of restoration of insulin production even in patients who’ve had type 1 diabetes for more than a decade.”

According to the release,

BCG is known to elevate levels of the immune modulator tumor necrosis factor (TNF), which previous work in Faustman’s lab showed can temporarily eliminate the abnormal white blood cells responsible for type 1 diabetes in both humans and mice.

Most participants treated with BCG showed increases in both the death of autoreactive T cells and in levels of the protective regulatory T cells. A temporary but statistically significant elevation in C-peptide levels, suggesting a restoration of insulin production, was also observed in the BCG-treated patients. Unexpectedly, the same responses were seen in one of the placebo-treated patients who, after enrolling in the study, coincidently developed infection with the Epstein-Barr virus, which is known to induce expression of TNF.

The research was presented Monday at the American Diabetes Association scientific sessions in San Diego