Chopra and his team first discovered asprosin in 2016, almost by accident. They were studying neonatal progeroid syndrome, a genetic disorder in which people are extremely thin, and found that, compared to people without the syndrome, people who had it were severely lacking in a previously unknown hormone they termed asprosin. In the new study, published in the journal Nature in November 2017, Chopra and his team found that the converse was true: Asprosin was extremely elevated in obese humans as well as mice.
They engineered an antibody that neutralizes the activity of the hormone in the bloodstream and injected it in obese mice, who exhibited reduced appetite and significant weight loss, as well as other benefits.
"The diabetes got better, and so did the obesity," Chopra said. At the same time, there appeared to be less of a risk for hypoglycemia, a common side effect of insulin.
"It would be fantastic for our lab or anybody to find an agent that can be injected once or twice a month and can reduce people's cravings for food and through a different mechanism reduce the glucose in the blood that causes the diabetes," Chopra said. The scientists also hope to develop a medication for neonatal progeroid syndrome by upping asprosin.
The latest study represents a "big step forward in understanding" how asprosin works "and also thinking of potential therapies and ways that can be used," said Evans, who was not involved in the research. There is "high potential" that the research on asprosin could lead to a drug "addressing important health problems," with few existing pharmacological remedies, Evans said. "It seems a good candidate in translating to human trials."
"Using an antibody is a particularly powerful approach, Evans said. "There's a lot of cleverness in the science." Asprosin, found in all animals, is involved in the starvation cycle, an evolved response ratcheting up hunger, as well as the energy to pursue food. "Even though it was not seen before, this is a very easy entry point."
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Evans also has reservations. Asprosin is but one of many hormones and other biological processes that interact to determine appetite, weight and disease. And we still know very little overall about how it interacts with those systems. He also cites safety concerns. Animals often stop eating in response to pain. For non-verbal mice, "we have a hard time telling how they feel. It could reduce appetite by making animals not feel good or nauseated," he said.
"This could be a critically important new hormone. It is clearly a major discovery and very intriguing," said Roger Cone, director of the University of Michigan LifeSciences Institute. Immediately after asprosin was discovered, Cone started trying to independently replicate Chopra's results.
Cone called the latest study "exciting for a number of reasons," praising the novelty and elegance of the science. But he also urges realistic caution, recalling that when Leptin, another major hormone involved in regulating appetite, was first discovered, it was also hailed as a potential breakthrough, "yet more than 20 years later there have been few applications."
Chopra readily admits these are early days. "We have understood the identity of asprosin, but we still don't know much about how it works. For instance, although we know it crosses the blood-brain barrier, we don't know where it binds in the brain."
Chopra hopes to answer questions like these in more animal studies, which he and his team are conducting as they pursue drug development. "There are hundreds of thousands of things that aren't discovered yet," he says.
— By Roni Jacobson, special to CNBC.com