A novel injection therapy could restore cognitive function in people with Down syndrome

The promising results led to improved not only cognitive function but also brain connectivity.
Mert Erdemir
Injection therapy
Injection therapy


An Inserm team at the Lille Neuroscience & Cognition laboratory is working with scientists at Lausanne University Hospital to evaluate the effectiveness of GnRH injection therapy in enhancing cognitive functions in a small group of Down syndrome patients, according to a press release published on Eurekalert.

Down syndrome is the most common chromosomal condition in the United States. According to the Centers for Disease Control and Prevention, about one in every 6,000 babies born in the U.S. has Down syndrome. It causes various symptoms, such as deterioration in cognitive capacity.

77 percent of those who have the syndrome have symptoms that resemble those of Alzheimer's disease as they get older. Typical neurodegenerative illnesses and gradual loss of scent are also commonly seen from the prepubertal period, with males potentially experiencing sexual maturation problems.

Restoring physiological GnRH system function

Recent research has revealed that the neurons producing gonadotropin-releasing hormone, which is known for controlling reproduction through the hypothalamus, may also have an impact on other brain regions that may be involved in cognitive processes.

With this idea in mind, the research team studied the mechanism that regulates GnRH in mouse models of Down syndrome. The results have shown five strands of microRNA, which regulate the production of this hormone, are dysfunctional. This extra chromosome leads to abnormalities in the neurons that secrete GnRH.

The Inserm researchers, who indicated the direct correlation between abnormal GnRH secretion and the mice's growing cognitive and olfactory deficiencies, were also able to show that cognitive and olfactory functions in trisomic mice can be recovered by restoring physiological GnRH system function.

Following a protocol identical to the one used in humans, the researchers tested the effectiveness of pulsatile GnRH treatment on cognitive and olfactory deficits in trisomic mice. The team showed that mice's olfactory and cognitive skills had returned after 15 days.

The next step was a pilot clinical trial in patients to evaluate the efficacy of the treatment. Via a pump on the arm, seven men with Down syndrome between 20 and 50 years old got one subcutaneous GnRH dose every two hours for six months. Cognitive and olfactory tests, MRI scans, and other procedures were carried out before and after the treatment.

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Six out of seven patients demonstrated an improvement in cognitive function, including better three-dimensional representation, a better understanding of instructions, and better reasoning, attention, and episodic memory. On the other hand, the therapy had no effect on the ability to smell. The CHUV Department of Clinical Neurosciences' brain imaging study, which found a significant increase in functional connectivity, confirmed these approaches to improve cognitive capabilities.

"Maintaining the GnRH system appears to play a key role in brain maturation and cognitive functions," explains Prévot. "In Down syndrome, pulsatile GnRH therapy is looking promising, especially as it is an existing treatment with no significant side effects," adds Pitteloud.

These encouraging results now pave the way for a bigger trial that includes women to confirm the efficacy of this treatment in people with Down syndrome and other neurodegenerative illnesses, including Alzheimer's.

The results of the study were published in the journal Science on September 1.

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