Although recruitment of participants ages 8-65 has been completed, enrollment of children ages 4-7 is still ongoing. To date, 4 children in this age group have been enrolled at the C.S. Mott Children’s Hospital at Michigan Medicine. More information on contacts and locations is available here.
Besides growth hormone deficiency, hypothyroidism (low levels of the thyroid hormone), delayed puberty, and behavioral issues, one of the most common symptoms of PWS is hyperphagia, or extreme hunger and obsession with food. This severe complication may lead to substantial weight gain and childhood obesity. It also increases patients’ risks of developing disorders such as diabetes, high blood pressure, and hypoventilation.
“This debilitating side effect can provoke children with PWS to raid pantries at home or steal food from school. I know parents that have to put locks on their kitchen cabinets,” Daniel Shumer, MD, pediatric endocrinologist at the Mott Children’s Hospital, said in a press release. “Living with hyperphagia can take a lot of mental energy from the child and those around them.”
In ZEPHYR (NCT03790865), researchers around the world are testing whether Millendo Therapeutics’ livoletide (AZP-531) may be an effective therapy for hyperphagia. The treatment candidate is an analog of unacylated ghrelin (UAG), one of two forms of the hormone ghrelin, intended to lower the amount of active ghrelin in the brain.
When the stomach is empty, acylated ghrelin (AG) — the other form of ghrelin — is released to stimulate eating. It also leads to fat deposits and insulin resistance. By blocking AG-induced hunger, UAG decreases fat deposits and insulin resistance. Yet, people with PWS have lower levels of UAG than those of AG.
The potential of the investigational livoletide was supported by the results of a Phase 2 trial, which showed that daily injections of 3-4 milligrams of livoletide for two weeks led to a significant decrease in hyperphagia and appetite in adolescents and adults with PWS.
The researchers says that, in addition to assessing livoletide’s efficacy in treating hyperphagia, ZEPHYR may help improve understanding of how the brain controls hunger or experiencing satiety. This could have implications for diseases other than PWS.
“Children with rare diseases are especially vulnerable, since there isn’t a lot of public awareness,” Shumer said. “When there isn’t awareness there aren’t many treatment options, and that’s isolating for famies.”
“It’s imperative there are people that work on novel treatments for conditions like this,” he added.
Although the efforts to develop livoletide are global, both the C.S. Mott Children’s Hospital and Millendo — which is sponsoring ZEPHYR — are based in Ann Arbor, Mich.
“Millendo Therapeutics is right in our backyard,” Shumer said. “It’s an Ann Arbor based invention and Michigan Medicine researchers work there. It’s something I’m so proud to be a part of.”