A new drug that is being developed may lessen the effects of learning difficulties caused by the genetic condition Down's syndrome. Children with the condition are not developmentally delayed at birth, but often fall behind as they grow older because of memory deficits. A new study in mice, published in the journal Science Translational Medicine, has identified the key brain defects responsible and has pointed out a strategy for dealing with them through medication. The US researchers, from Stanford University School of Medicine and Lucile Packard Children's Hospital, have said that the medication could also help protect against early onset Alzheimer's disease, which is especially common in the middle aged Down's syndrome community. Both conditions are linked to the same gene, known simply as APP, but this new study is the first to directly link APP with the specific type of brain degeneration responsible for Down's syndrome.
Around 60,000 people in Britain are affected by Down's syndrome and there is currently no cure. The risk of having a baby with the condition is about 1 in 940 for a 30 year old woman, but closer to 1 in 85 for a 40 year old woman. The increasing average age of mothers has therefore meant that the number of conceptions of babies with Down's syndrome has increased dramatically in the past 20 years. However, there has been a parallel increase in screening and termination meaning that the overall proportion of babies born with the condition has remained roughly fixed at about 1 in 750. Down's syndrome is caused by an extra copy of chromosome 21, more specifically a second copy of the gene APP on chromosome 21.The condition is characterised by memory deficits that make it difficult for the brain to collect and process experiences. Forming new memories in this way underpins the development of learning and is crucial to normal cognitive development. This explains why those with Down's syndrome often fall behind, with children as young as 2 performing worse in basic cognitive tests. Most people with the condition survive into middle age, but exhibit symptoms similar to those of dementia around the ages of 50 to 60.
Normally when contextual and relational memories are formed neurons, in an area of the brain known as the hippocampus, receive the chemical norepinephrine from another area of the brain known as the locus coeruleus. The new study involved mice that were genetically engineered to mimic Down's syndrome in that, like humans with Down's syndrome, the mice had experienced early degeneration of the locus coeruleus. These engineered mice exhibited abnormal behaviour such as not building nests when placed in new and unfamiliar cages. However, when the engineered mice were given certain drugs (that were converted to norepinephrine in their brains) improvements were quickly noticed. Within hours they were just as good at nest building and showed improved performance in the other related tests. Further detailed examination of their brains showed that the hippocampal neurons had responded well to the treatment.
'We were very surprised to see that, wow, it worked so fast,' said Ahmad Salehi, leader of the study. However, he warned that the effect of the drugs also wore off quickly, and seemed to have disappeared altogether when the mice were tested two weeks later. Salehi added: 'If you intervene early enough you will be able to help kids with Down's syndrome to collect and modulate information.' Others involved are also optimistic. The findings give 'a ray of hope and optimism for the Down syndrome community for the future,' said Dr Melanie Manning, director of the Centre for Down’s syndrome at Lucile Packard Children's Hospital.
Although promising, research reported in the LA Times this week shows that not all parents would welcome the prospect of a cure for their child's Down's syndrome. In a survey carried out by scientists at the University of British Columbia in Vancouver, 27 per cent of parents said they would not cure their children, and another 32 per cent said they were unsure. 101 Canadian parents of children with Down's syndrome took part in the study, which was presented at the National Society of Genetic Counselors' annual education conference in Atlanta.