Memory drug trialled in people with Down's syndrome

The first drug specifically designed to improve cognitive impairment in Down's syndrome is being tested in humans.

David Nutt, former drug policy adviser to the UK government, told delegates at the Festival of Neuroscience in London yesterday that he is collaborating with pharmaceutical company Roche in trials of a substance it developed, called RG1662.

RG1662 reverses the effects of a chemical messenger in the brain called GABA ? a neurotransmitter that inhibits brain activity. The drug acts on a specific type of brain receptor found mostly in the hippocampus, a part of the brain involved in memory. It is thought that it will reduce excessive inhibition in the hippocampus, thought to underlie memory and learning problems commonly seen in people with Down's.

The study is currently assessing safety and tolerability of the drug in 33 adults with Down's, but researchers will also measure motor skills, reaction time and memory, and compare the results with those of people taking a placebo. The aim is to find appropriate doses to use in a full clinical trial, which Nutt says should happen this year.

Targeting GABA

Roche said in a statement that RG1662 may help people with Down's as it has "a unique pharmacology that enables the targeting of GABA over-activity mainly in brain systems important for cognition, learning and memory".

Luca Santarelli, head of neuroscience at Roche, hopes that the drug will enhance the communications skills of people with Down's "and ultimately help them have greater independence".

Nutt studied a similar drug in 2007 and found it blocked memory problems in people impaired by alcohol. "It didn't have any impact on whether you could stand straight, so people were still falling over, but they could remember everything," he says.

Meanwhile, another group tested the drug on a mouse model of Down's, finding that it normalised memory function (Journal of Psychopharmacology, doi.org/bxscgg). Unfortunately, the drug caused kidney problems, so development was halted. RG1662 does not appear to have this side effect.

Dai Stephens at the University of Sussex, UK, who helped pioneer this class of drug for treating memory problems in old age, cautions that there may be costs associated with the benefits, such as a degradation of memory from before the drug was taken. "I think that you would have some symptomatic changes ? whether they would be therapeutically significant is an empirical question, but it is good someone is testing it."

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