Lettuce-made therapy stops uncontrolled bleeding in animals

A lettuce-made therapy has shown great promise in recent studies. People with haemophilia require regular infusions of clotting factor to prevent them from experiencing uncontrolled bleeding. But a significant fraction develop antibodies against the clotting factor, essentially experiencing an allergic reaction to the very treatment that can prolong their lives.

Haemophilia, also spelled hemophilia, is a mostly inherited genetic disorder that impairs the body’s ability to make blood clots, a process needed to stop bleeding. This results in people bleeding longer after an injury, easy bruising, and an increased risk of bleeding inside joints or the brain.

Researchers from the University of Pennsylvania School of Dental Medicine and University of Florida, United States (U.S.), have worked to develop a therapy to prevent these antibodies from developing, using a protein drug produced in plant cells to teach the body to tolerate rather than block the clotting factor.

Successful results from a new study of the treatment in dogs give hope for an eventual human treatment. A professor in Penn Dental Medicine’s Department of Biochemistry and director of translational research, Henry Daniell, was the senior author on the study, collaborating on the work with his former advisee, Roland W. Herzog, a professor at the University of Florida and lead author on the paper.

The study titled “Oral Tolerance Induction in Hemophilia B Dogs Fed with Transplastomic Lettuce” was published in the journal Molecular Therapy.

“The results were quite dramatic,” Daniell said. “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.”

The study made use of Daniell’s patented plant-based drug-production platform, in which genetic modifications enable the growth of plants that have specified human proteins in their leaves. In the case of haemophilia, the researchers’ aim was to prevent individuals with haemophilia from developing antibodies that would cause a rejection of life-saving clotting-factor infusions. The researchers had the idea that ingesting a material containing the clotting factor, such as the transformed plant leaves, could promote oral tolerance to the factor protein, just as children fed peanuts early in life are less likely to develop an allergic reaction.

Also, new research involving Monash University biologists in Victoria Australia has debunked the view that males just pass on genetic material and not much else to their offspring. Instead, it found a father’s diet can affect their son’s ability to out-compete a rival’s sperm after mating. The study sought to understand if the nutritional history of fathers had an effect on their sons. Experiments were carried out in the fruit fly, which shares many similar pathways and characteristics with human genes. One of the lead authors of the study, Dr. Susanne Zajitschek from the School of Biological Sciences, said the study highlighted the importance of the paternal environment on future generations, even a long time before offspring were produced.

“Our study found that males that were raised on either high or low protein diets, but spent their adulthood on an intermediate diet, produced sons that had large differences in gene expression, which most likely contributed to the resulting differences in sperm competitiveness,” Dr. Zajitschek said.

“They differed in their ability to sire offspring, with the high-protein dads producing sons who were doing much better in sperm competition, which means their sperm was more likely to win against a competitor’s sperm within the female tract.We also found that the immune response genes were less active in sons of low-protein fathers, while metabolic and reproductive processes were increased in sons of fathers on a high protein diet,” she said. The research, published in Biology Letters, is one of only a few studies to have so far reported trans-generational effects in relation to diet quality, and one of the first to report on the post-copulatory advantages conferred by parental diet.