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Patients with hemophilia are often forced to live in a bubble. Even the smallest cut can cause significant blood loss, and often times these minor accidents can also cause internal bleeding that affects organs and threatens life. Some treatments have proven effective at keeping hemophilia at bay, at least to a degree, yet some groups of patients do not respond well because their immune system attacks the treatment. Scientists at University of Florida Health and the University of Pennsylvania may have provided a viable solution to this group after they engineered plants that twat the immune response to tolerate rather than attack the clotting factors.

Plants that stop bleeding

Hemophilia is a rare, inheritable bleeding disorder in which the blood doesn’t clot normally. People born with hemophilia have little or no clotting factor. Clotting factor is a protein needed for normal blood clotting. There are several types of clotting factors. These proteins work with platelets – small blood cell fragments that form in the bone marrow – to help the blood clot.

Hemophilia A, the most common form,  occurs when babies are born with a defective gene on the X chromosome. Because girls have two X chromosomes — giving them two shots at having a working version of the gene — the disease typically only affects boys. Worldwide, one in 7,500 male babies is born with this disease.

To treat hemophilia, doctors prescribe a treatment where certain proteins are injected to stem the flow from a wound. After receiving factor VIII treatments (the clotting proteins), some 20 to 30 percent of patients, however, develop antibodies which attack the proteins instead of letting them do their job. These antibodies are known as inhibitors.

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“The only current treatments against (antibody) formation cost $1 million and are risky for patients,” said Henry Daniell, Ph.D., interim chairman of biochemistry at the University of Pennsylvania School of Dental Medicine and a co-author on the study. “Our technique, which uses plant-based capsules, has the potential to be a cost-effective and safe alternative.”

Daniell and colleagues engineered tobacco plants that were modified to express factor VIII DNA and another substance that can safely cross the intestinal walls and enter the bloodstream. These resulting veggies were fed to hemophiliac mice twice each week for two months and compared them with mice that were fed unmodified plant material. They then gave the mice infusions of factor VIII, just as human hemophilia patients would receive. As expected, the control group formed high levels of inhibitors. In contrast, the mice fed the experimental plant material formed fewer inhibitors — on average, seven times fewer.

Subsequent research showed the mice who were fed the modified tobacco produced more signaling molecules associated with suppressing or regulating immune responses.

The researchers also wanted to see how the solution would behave in mice who had already developed antibodies to factor VIII proteins.

After two to three months of feedings with the plant capsules, the mice had three to seven times fewer antibodies than before the treatment began.

“We have been looking for a way to induce immune tolerance in hemophilia for a while,” said UF co-author Roland Herzog, Ph.D., a professor of pediatrics in the UF College of Medicine and a member of the UF Genetics Institute. “Oral tolerance is ideal is because you are feeding them something specific that addresses the problem and you don’t have to use drugs that suppress the immune system. It’s not invasive. You’re not manipulating patients’ cells. It would be an ideal way to do it.”

It’s important to note that potential human patients – if the treatments is found to work in clinical trials – would have to take both the plant solution (most likely made  form lettuce, instead of tobacco) and treatment. The researchers have already begun work with a leading pharmaceutical company to bring their solution to the market.

“With multimillion-dollar funding from a global pharmaceutical company and their decades of expertise in bringing numerous protein therapeutics to the clinic, we¹re excited to take lettuce capsules producing human blood clotting factors to the clinic soon,” Daniell said.

Findings were reported in the journal Blood.