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Husker project examines milk as a possible cancer fighter | Nebraska today

In health care, perhaps no word sends a scarier message than “cancer.” Brain tumours, for example, are proving particularly resistant to current treatments. Only 5% of patients with this disease survive more than three years, and the median survival time is 10 to 14 months.

But an innovative research project led by scientists at the University of Nebraska-Lincoln holds the potential for a breakthrough. In a federally funded project, Janos Zempleni, a professor in the Department of Nutrition and Health Sciences, and his colleagues at Husker are researching a surprising way to use milk as a vehicle to deliver cancer therapies to the brain.

The concept isn’t as fancy as it sounds – it’s backed up by recent science. Preliminary findings in recent years show that it is possible to manipulate the body’s genetic function to reduce tissue growth, including cancerous tumors. Scientists achieve this by directing a type of gene regulator known as siRNA to the targeted tissue. Genetic signaling carried by siRNAs shuts down gene function that allows new tissue to grow.

But converting this preliminary discovery into an effective medical treatment has encountered obstacles. So far, scientists have not been able to find an efficient way to deliver the genes consistently to the targeted area and in sufficient quantity.

It turns out that milk offers a good chance of solving the problem. Humans take in siRNAs through food, according to recent research. And milk, Zempleni found, stands out for its robust ability, once ingested, to help genes build up naturally in the brain.

In their project, Husker researchers will perfect milk-based techniques for efficient gene delivery. Specifically, the project will use siRNA genes carried in milk to arrest the growth function of a gene known as HDI1, whose mutations lead to brain tumors. The research also offers hope in the fight against rare brain-focused genetic abnormalities affecting young children, said Zempleni, Willa Cather Professor of Molecular Nutrition and director of the Nebraska Center for the Prevention of Obesity Diseases.

the WE The Department of Agriculture provided a grant of $630,000 to support the project. Zempleni will lead the research, working with Forrest Kievit, assistant professor of biological systems engineering, and Jiantao Guo, associate professor of chemistry. USDAThe National Institute of Food and Agriculture provided the grant.

The long-term potential of this science is “enormous. That hasn’t been done at all yet,” said Zempleni, a Fellow of the American Association for the Advancement of Science and winner of the 2015 Omtvedt Innovation Award from the Agricultural and Natural Resources Institute.

Zempleni and his colleagues will use genetic science and chemistry to load exosomes, a naturally occurring nanoparticle in milk, with therapeutic material including siRNAs. Loading the material onto cow’s milk exosomes would first require genetically modifying the cow, an extremely delicate task. Thus, researchers will rather cultivate Mac-T cells (similar in genetic makeup to cow’s milk cells) in the lab to produce exosomes, then direct them to brain tumors in mice.

The researchers aim to develop techniques that achieve two goals: to ensure that siRNAs efficiently and consistently reach tumors and that siRNAs accumulate in sufficient quantities to reduce tumor growth.

If this technology proves viable, large-scale production of exosomes will be required to meet real patient demand. Laboratory cultures can only provide a low volume of exosomes. A cow, on the other hand, can provide sufficient numbers through her milk.

So the Husker researchers aim, in the long term, to take a big step forward if their current research achieves its gene delivery goals: they will seek to develop a genetically modified cow.

Such a cow, writes Zempleni, would secrete “milk exosomes conducive to maximum delivery of RNA therapeutics to brain tumors in human cancer patients.

The pharmaceutical industry already uses this general concept. This is called biopharmacy, that is, the use of animals in the production of medical treatments. The drug Atryn, used to prevent blood clots in patients with a rare disease, is derived from the milk of genetically modified goats.

“With our technology, you can actually use these milk exosomes, attach the appropriate functionality, and provide treatment for people with these rare diseases,” Zempleni said. “I think it could be a game-changer if we get a funding agency to take the risk of developing these animals. It is a difficult task. With the Mac-T cells are relatively easy, but taking that to cattle, a goat or a cow, is very, very complicated.

Husker research was pioneering in identifying the importance of milk as a potential gene delivery mechanism. In 2014, Scott Baier – a PhD candidate in Zempleni’s lab – proposed an initial research project on the topic, resulting in a Journal of Nutrition article that he, Zempleni and other Husker colleagues co-authored. . Since then, the article has been academically cited nearly 300 times. Baier received his doctorate in nutritional sciences from Nebraska in 2015 and is now senior director of medical strategy at Vaniam Group, a company specializing in transformative cancer therapies in Dallas.

Zempleni’s path to scientific exploration of genetics and food science began during his teenage years in his home country of Germany.

“I loved biology, but at that age I loved going fishing. I loved all these species of fish that came from Germany,” he said.

Over the next few years his interests broadened, gradually shifting “from fish to biology to science”.

“I was torn between biochemistry or nutritional science,” he said. “I think that looking back, I made the right choice by opting for the science of nutrition. It is a very comprehensive approach which allowed me to deepen my knowledge of biochemistry and molecular biology. So , I think I have the best of both worlds.