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UNL researchers wonder if milk can bring therapies to the brain | Education

OMAHA – According to the dairy industry’s advertising campaign of the 1980s, milk is good for the body.

A University of Nebraska-Lincoln researcher takes the old slogan one step further, studying whether nanoparticles naturally found in milk, called exosomes, can be used to deliver therapies – from cancer treatments to gene therapies – to the brain and possibly to other organs and tissues.

Janos Zempleni, a professor in the department of nutrition and health sciences at UNL, and his team recently demonstrated that milk exosomes cross the blood-brain barrier, the network of blood vessels and tissues that prevents substances harmful to reach the brain. Typically, the blood-brain barrier prevents cancer drugs or other treatments from entering the brain.

The team’s nutritional research, which began in 2013, indicated that exosomes have a number of properties that make them perfect candidates for drug delivery, Zempleni said. In cow’s milk, natural exosomes already carry eight different types of RNA, all with different functions, as well as fats and proteins.

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Janos Zempleni, a professor in the department of nutrition and health sciences at UNL, and his team recently demonstrated that milk exosomes cross the blood-brain barrier.


CRAIG CHANDLER, UNL


The exosomes in milk are also stable and survive digestion in the gastrointestinal tract, which would allow doctors to administer the drugs they carry by mouth rather than by intravenous infusion. In addition to being able to cross the blood-brain barrier, they can also cross the placenta, meaning they could be used to deliver therapies to the fetus if needed. Researchers can also use proprietary technology to modify exosomes to enhance these properties to make them deliver cargo to more targeted tissues and evade the immune system.

The researchers currently have a $630,000 grant from the US Department of Agriculture to continue their work, using the deadly brain cancer glioblastoma as a model.

With cancer, research involves using exosomes from milk to transport a type of gene regulator called siRNA into the brain. Officially known as small interfering RNAs, the small pieces of genetic material silence gene expression.

“So what we’re doing in the context of brain cancer is we’re turning off cancer-promoting genes by delivering siRNAs,” Zempleni said.

The researchers also have separate funding from a group called the SynGAP Research Fund, an international organization made up primarily of families with children who carry a SynGAP gene mutation. Due to the mutation, affected children suffer from cognitive impairment, developmental delay, seizures, and autism spectrum disorder.

In this case, Zempleni said, the team works to deliver mRNA, or messenger RNA, to the brains of affected children to make more of the normal SynGAP protein, which is found at junctions or synapses. between nerve cells where cell-to-cell communication takes place. These connections act as the “wiring” in the circuits of the brain.

For now, the researchers are working on a line of cells from a cow’s udder that make exosomes in the lab nearly identical to those in cow’s milk, Zempleni said. The team can make genetic changes in cells and test how the changes affect both the exosomes themselves and their ability to deliver drugs to diseased tissue.

Cell cultures, Zempleni said, produce enough exosomes to work in mice, which is what the researchers are currently doing. But treating a human patient would require many, many vials of cells.

To increase production, the researchers eventually want to move on to producing exosomes in cattle. “If you have a cow that gives 20,000 pounds of milk a year, you can imagine an endless supply of exosomes,” he said.

This step, however, will require the creation of a genetically modified or transgenic cow or goat that produces exosomes optimized for drug delivery into its milk.

Producing such an animal, Zempleni said, would take about eight years. And it’s expensive. But producing such animals would allow the dairy farmers who care for them to reap much more for the milk produced by the animals, a concept known as value-added farming.

The Food and Drug Administration approved in 2009 the first drug produced by cattle given a human gene. The drug, intended to prevent fatal clotting in people with a rare disease, is extracted from the milk of genetically modified goats. Other “biopharmaceutical” products are also in preparation.

“It’s really exciting,” Zempleni said of the UNL team’s research. “It provides many opportunities for nutrition and drug delivery. It (has) definitely potential for sick people. We can really make a difference there.