Hormone therapy can boost brain function in people with Down syndrome, study finds

A pilot study has suggested that regular doses of a hormone may help boost cognitive skills in people with Down syndrome.

Researchers fitted seven men with Down syndrome with a pump that delivered a dose of GnRH, a gonadotropin-releasing hormone, every two hours for six months.

Six of the seven men showed moderate cognitive improvements after treatment, including attention and the ability to understand instructions, compared to a control group that did not receive the hormone.

However, experts expressed concern about the methods used in the study and called for caution with the findings.

The team behind the work said brain scans of the participants, who were aged between 20 and 37, given the hormone, suggested they suffered changes in neural connectivity in areas involved in cognition.

“[People] with Down syndrome have a cognitive decline that starts in their 30s,” said Professor Nelly Pitteloud, co-author of the study from the University of Lausanne. “I think if we can delay this, that would be great, if the therapy is well tolerated [and] without side effects”.

Writing in the journal Science, Pitteloud and colleagues said they previously found that mice with an extra copy of chromosome 16 experienced an age-related decline in cognition and smell, similar to what seen in people with Down syndrome, who have an extra copy of chromosome 21.

In a series of experiments, the team found that regular doses of gonadotropin-releasing hormone increased both the sense of smell and cognitive performance of these mice.

Pitteloud said no side effects were seen in the participants and that the hormone is already used to induce puberty in patients with certain disorders.

“I think these data are, of course, very exciting, but we have to be cautious,” Pitteloud said. He said larger randomized control studies are now needed to confirm that the improvements were not driven by patients becoming less stressed during assessments and therefore performing better.

Professor Michael Thomas of Birkbeck, University of London, who studies the lifelong cognitive development of Down syndrome, said the results were exciting.

“For parents, this is good news: interventions can still provide lifelong benefits,” he said, although he noted that it is unclear how applicable hormone therapy would be for children.

However, Professor Andre Strydom, a specialist in intellectual disability psychiatry at King’s College London, said the mice used in the study were no longer considered a good model for Down syndrome, as their chromosome additional contains several genes other than those present on chromosome 21 in humans.

Elizabeth Fisher, professor of neurogenetics at UCL Queen Square’s Institute of Neurology, added that these differences meant it was unclear whether the mice’s cognitive and olfactory decline had the same cause as similar traits in people with Down’s syndrome.

Strydom also cautioned that the pilot study was very small with participants aware of the treatment they were receiving, while the assessment used for cognitive performance is not generally thought to be suitable for people with Down syndrome. “The cognitive results are not at all convincing,” he said.

Defending the work, Pitteloud said the similarities in cognitive decline and loss of smell between mice and people with Down’s syndrome meant that, while imperfect, the mouse model is useful.

While Strydom said efforts to improve the difficulties experienced by people with Down syndrome are welcome, the findings of the pilot study need to be replicated in other work. “There is a long way to go before it can be offered in the clinic,” he said.

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