GnRH could hold the keys to improved cognitive function in people with Down syndrome, as well as neurodegenerative diseases such as Alzheimer's, a pilot study suggests. A hormone injection therapy could help people with Down syndrome, as a new study found it to improve cognitive function and brain connectivity of a small group of people with the condition. The authors of the study, published in the journal Science, demonstrate the role that gonadotropin-releasing hormone (GnRH) appears to play in cognitive function and brain maturation. In a preliminary clinical trial in humans, they show its therapeutic potential in improving the cognition of people with Down syndrome. “In Down syndrome, pulsatile GnRH therapy is looking promising, especially as it is an existing treatment with no significant side effects,” study author Professor Nelly Pitteloud from the University of Lausanne said in a press release. Down syndrome is the most common chromosomal disorder. In the US, around 6,000 people – roughly one in every 700 – are born with the condition each year. Almost all cases are caused by an extra copy of chromosome 21, which can result in cognitive decline and various other clinical manifestations. The majority – 77 percent – of people with Down syndrome experience symptoms akin to those of Alzheimer’s disease as they age, and around half who live to 60 will actually go on to develop the neurodegenerative disorder. People with Down syndrome often lose their sense of smell, which is common with neurodegenerative diseases, and males with the condition may also experience sexual maturation problems. There is currently no treatment available for the cognitive or olfactory defects associated with Down syndrome. Investigating GnRH, a hormone released by the hypothalamus that plays a role in reproduction, the researchers of the new study are hoping to change that. In humans, GnRH is linked to Kallmann syndrome: characterized by olfactory defects, gonadal immaturity, and infertility. Previous research has found that GnRH-expressing neurons can act on brain regions outside of the hypothalamus, where they could influence cognition. In light of this, the team investigated its role in cognition using a mouse model of Down syndrome. They identified five strands of dysfunctional microRNA, which regulates GnRH production, plus abnormalities in the neurons that secrete GnRH. This would explain the decreased GnRH expression observed in the mice with Down syndrome. When they restored GnRH function of the mice, they found that cognitive and olfactory functions recovered within 15 days. The next step was to see if these findings could translate to humans. The team organized a small pilot trial, involving seven men with Down syndrome aged between 20 and 50. Each received an injection of GnRH via a pump on the arm every two hours for six months. Brain scans, as well as cognition and olfactory tests, were completed before and after the treatment. While it didn’t affect an individual’s ability to smell, the treatment did improve cognitive function and brain connectivity in six out of the seven people studied. Specifically, there were improvements in three-dimensional representation, understanding instructions, reasoning, attention, and episodic memory. “GnRH thus plays a crucial role in olfaction and cognition, and pulsatile GnRH therapy holds promise to improve cognitive deficits in [Down syndrome],” the authors write in their study. Of course, the trial is limited by its size, but a larger trial, this time including women, is imminent. With any luck, the researchers hope, it could lead to a treatment for cognitive issues associated with Down syndrome, and maybe other neurodegenerative illnesses, in the not-too-distant future. Source
