ORLANDO, Fla.—Postnatally enhancing the development of the hypothalamus appears to be a promising therapeutic approach in Prader-Willi syndrome (PWS), psychiatrist and researcher Tony Holland, MD, said in his keynote presentation at the Prader-Willi Syndrome Association’s 2023 National Convention.
Recent research suggests genetic engineering is a less relevant approach, said Dr. Holland, who is president of the International Prader-Willi Syndrome Organisation (IPWSO), based in Cambridge in the United Kingdom.
“That’s the question we should be addressing … why is the hypothalamus poorly developed? Can you in any way manipulate that?,” he said. “Is there anything you can do that improves that? That would be, if you like, a more preventative approach.”
Specific tactics of treatments, he explained, could include enhancing afferent inputs to the hypothalamus, acting on hypothalamic pathways, and modifying post-hypothalamus reward and satiety pathways. Therapeutics are being studied for using each of these approaches to treating PWS.
Transformative research found that people with PWS had a significantly smaller hypothalamus than a control group of people with obesity and an age-matched control group, said Dr. Holland, also an emeritus professor of psychiatry at the University of Cambridge. Furthermore, researchers found that a smaller hypothalamus size correlated with higher hyperphagia scores.
These findings “suggest the possibility of a gene receptor availability as a central deficit” in PWS, he explained.
Aside from hyperphagia, a central component of PWS, Dr. Holland’s presentation on mental health and behavior in PWS also covered emotional outbursts and psychotic illness.
Among people with PWS, 60% to 80% have high rates of emotional outbursts. Research in the UK has shown that some psychological attributes are linked with different patterns of activation in the brain, Dr. Holland said.
“[Emotional outbursts] are a major cause of parental stress and of placement breakdown,” he said. “We could transform the lives of people with Prader‑Willi syndrome if we had a treatment for these emotional outbursts.”
Holland T. Keynote presentation. Oral presentation at: PWSA | USA 2023 National Convention; June 21, 2023; Orlando, FL.