Single injection for life long treatment of Hemophilia B

Hemophilia B can be treated for life with one single injection, containing disease-free liver cells that can produce their missing clotting factor, Salk researchers.Mostly hemophilic B patients’ bodies can't properly form blood clots, so constant injections to replenish their clotting factors is required.

Ramaswamy et al. show that hepatocytes transplanted into a mouse model can alleviate symptoms of hemophilia B. Induced pluripotent cells from patients with hemophilia B can be gene-corrected and converted to hepatocyte-like cells for cell therapy. This provides evidence for potential treatment of monogenic diseases of the liver using cell therapy.

Hemophilia B is caused by defects in the gene for a protein called clotting factor IX (FIX). Hemophiliacs may make reduced amounts of the protein, or lack a functional version altogether, leading to life-threatening delays in blood clotting. Currently, patients are treated with injections -- as often as a few times a week -- containing FIX made in animal cells and then purified. But the approach is expensive, time-consuming and can become less effective over time.

Recently, Salk scientists developed a new approach, treating mice genetically engineered to have hemophilia B with strands of messenger RNA encoding the FIX gene. Like the standard treatment, however, this required repeat injections each time levels of the messenger RNA becomes low. So the scientists transplanted healthy liver cells, capable of producing FIX, into patients.

The researchers collected blood samples from two human patients with severe hemophilia B, who are unable to produce FIX. Then, in the lab, they reprogrammed the cells into induced pluripotent stem cells (iPSCs), which have the capability to turn into many other cell types, including liver. Using CRISPR/Cas9, a tool that can alter genes, they then repaired the mutations in each patient's FIX gene. Finally, they coaxed those repaired cells to develop into liver precursor cells called hepatocyte-like cells (HLCs) and transplanted them into mice with hemophilia B.

The HLCs was then transplanted through the spleen to distribute the cells uniformly in the liver.

Besides the new HLCs producing FIX, they also produced enough of the protein to allow the mice to form normal blood clots, and the cells continued to survive and produce FIX for at least a year after the transplantation.

This concept can be utilized In people with hemophilia, using their own cells to generate healthy HLCs, then transplanting them back into their bodies, which could help avoid the immune complications that often accompany cell therapies. The study believes that more research has to be done in this field.

The finding was published in the journal Cell Reports.