Denise Ney is dishing up new options to people living with a rare metabolic disorder. And the next big thing in weight loss may be lunch for her lab mice.
One mother’s determination can shape the course of science. It can launch decades of research, discovery and a breakthrough at long last – a test that is saving children around the world, though it came too late to save her own.
In the cool Norwegian spring of 1934, Borgny Egeland was armed with a hypothesis. Dismissed by the leading medical centers of Europe, she marched undaunted into Oslo University Hospital, her two young children in tow.
She had watched as her daughter, born bright and healthy, slipped deeper into mental retardation. The six-year-old spoke few words and limped. Tragedy struck twice. A son, age four, was succumbing even faster, unable to talk, walk or feed himself.
Why was this happening? And did it have something to do with the strange odor in the children’s hair, sweat and urine? The scent was so powerful it aggravated their asthmatic father.
The physician examined the children out of courtesy. Like his colleagues he observed a hopeless case of ‘feeblemindedness.’
But in his attic laboratory above the medical ward, he conducted one last test on the children’s urine using a few drops of acid. It was supposed to turn the sample a reddish color. It turned green. He called for more samples.
In her sunlit office on the UW–Madison campus, Denise Ney finishes the story.
“The mother brought in 22 liters of urine over a period of months. Using old-fashioned organic chemistry, the physician isolated a phenylalanine compound and concluded it was building up in their blood.”
Today, after half a century of research, the children would be screened soon after birth and diagnosed with a rare condition called phenylketonuria, or PKU. The inherited disorder occurs in about 1 in 13,000 newborns in the United States.
People with PKU lack an enzyme needed to process phenylalanine, an amino acid found in most common foods. PKU patients must adhere to a lifelong draconian diet – e.g., special synthetic formula, low-protein pasta, a cup of broccoli – or the phenylalanine accumulates in their bodies. High levels can wreak mental impairment and physical breakdown.
Ney, a professor of nutritional sciences and D2P advisory board member, is an internationally recognized PKU expert. She can tell stories about the patients she’s come to know over the years: the young girl who wanted a PKU mouse for a pet; the man who strayed from his strict diet as a teenager and can’t walk without a crutch; the Wisconsin woman who’s lived a rich and interesting life because she was diagnosed early.
“Her brother was not diagnosed, and lives in an institution,” Ney says. “That’s when the meaning of this work really hits you.”
Ney’s research focuses on developing safer, more palatable medical foods based on a protein found in cheese whey called glycomacropeptide (GMP). GMP is ideal for patients because it is the only naturally occurring protein to contain so little of the dangerous amino acid.
Interdisciplinary teams from the Waisman Center and the Wisconsin Center for Dairy Research have helped transform GMP protein isolate into a smorgasbord of tasty meals, bars, spreads and sports drinks. The normalized foods encourage patients to stick to their diet.
A translational research home run.
Now, support from the Accelerator Program is helping Ney take the next step in GMP investigation. It turns out, the protein may have health benefits beyond the niche PKU market. It appears to help female mice burn fat and build stronger bones.
No diet product currently on the market combines these two benefits. If GMP works the same way in humans, it could give new hope to women trying to lose weight or suffering from osteoporosis. Female athletes may stand to gain as well. The commercial potential is significant.
But it’s too early to tell. Ney and her team are about halfway through a major rodent study trying to pin down the effects of a GMP diet in the general population.
A bluish X-ray image of a mouse skeleton flickers on Ney’s computer screen. She explains how DXA scans measure bone mineral density, and what fatty acid oxidation assays reveal about metabolism.
So far the results are tantalizing. Even if GMP can’t prevent the mice from gaining weight, it may help them lose it faster and develop bigger, stronger bones. “To my knowledge we’re the only ones putting these two things together. That’s special. That’s the story of this Accelerator project.”
What’s the connection between less fat and stronger bones? Ney points to a recent study that suggests that early in their development, cellular precursors have a choice – become a bone cell or become a fat cell.
“The less fat you make, the more bone cells you make,” says Ney. “We think this is being programmed by consuming GMP.”
There’s an interesting commercial angle to this research. Presently, no company in the United States produces GMP (Ney orders her supply from Denmark). If there were a larger market for GMP, a company closer to home may get involved, driving down the cost of PKU medical foods as a result.
And after all, GMP comes from making Wisconsin’s favorite product. Cheese.
One company in North America has expressed interest in Ney’s latest work and is waiting to learn more. But she’ll need the rest of the year to work through her data and publish her findings.
In the meantime, Ney reflects on the many patients, food scientists, advocates and clinicians that have advanced GMP research to its current state.
“I don’t think there are many campuses in the world that could pull this off. We have all the pieces here. It’s the Wisconsin Idea.”
This story was originally published on the Wisconsin Alumni Research Foundation website.