Plant-made Therapy for Hemophilia Treatment

Hemophilia is a genetic disorder which impairs the ability of the body to make blood clots. These patients may require regular infusions of clotting factor to prevent uncontrolled bleeding. But a significant fraction found to develop antibodies against the clotting factor which can experience an allergic reaction to the treatment that can prolong lives. A research team from the University of Pennsylvania School of Dental Medicine and University of Florida have found a therapy that can prevent the development of antibodies by using a protein drug that is produced in the plant cells. This therapy can train the body to tolerate, rather than blocking the clotting factor.

The study showed promising results when treated in dogs which could further be treated on humans.

The research work was published in the journal Molecular Therapy.

Daniell, said, "The results were quite dramatic."

"We corrected blood clotting time in each of the dogs and were able to suppress antibody formation as well. All signs point to this material being ready for the clinic."

Genetic modifications may help the plant to grow and have specific human proteins in their leaves. The research team aimed to prevent hemophilia individuals from developing antibodies as this could cause a rejection of life-saving clotting-factor infusions.

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The researchers also had an idea of ingesting a material that contains the clotting factor (transformed plant leaves) which can promote tolerance for factor protein.

The technique has also shown promise in experiments that were carried before, feeding the hemophilia A plant material that contains the clotting factor VIII can reduce the formation of inhibitors to the factor.

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In the recent study, the research team focused on Hemophilia B, a rare form of the disease that occurs due to the deficiency of clotting factor IX. Modified lettuce which produced a fusion protein that contains factor IX and the cholera non-toxin B subunit was produced by the research team.

The cholera non-toxin B subunit may help the fused protein to cross the intestinal lining as the gut microbes are capable of digesting the lettuce cells, while the cell walls of the plant may protect the clotting factor from digestion in the stomach. These lettuce plants were grown in nutrient dense oxygenated water.

The research team ensured that the therapy could work in animal models that are closer to humans and were trialed in dogs with hemophilia B.

Research Study
The study headed by Timothy Nichols of the University of North Carolina was conducted on two dogs. The dogs were given freeze-dried lettuce material with bacon flavor that was sprinkled on their food twice a week for 10 months.

Since there were no negative effects for the treatment, the research team included four dogs which were fed with lettuce material for four weeks. These dogs were also receiving weekly injections of factor IX, that was continued for eight more weeks. Four others were also considered as control and they only received injections.

The study findings found that all the four dogs in the control group was found to develop significant levels of antibodies against factor IX and two of them had anaphylactic reactions which required antihistamine administration.

While in the experimental group, three out of four dogs had a minimal level of one type of antibody, IgG2 and no detectable levels of IgG1 or IgE. However, the fourth dog in the experimental group was found to have only partial response to the treatment. The research team also believed that the partial response may be due to a pre-existing antibody to human factor IX.

The levels of the IgG2 antibody were 32 times lower in the treated dogs when compared to the control.

The dogs did not show any side effects and also did not show any signs of toxicity from the treatment.

The author concluded that the results were found to be encouraging and "Looking at the dogs that were fed the lettuce materials, you can see it’s quite effective."

"They either developed no antibodies to factor IX, or their antibodies went up just a little bit and then came down."

Further research work may include additional toxicology and pharmacokinetic studies before applying an investigational new drug application with FDA.



Source-Medindia