Public release date: 26-Nov-2008
– Inhibiting the neurotransmitter GABA
– When the pups were born, they reached developmental milestones at the same time as normal mice
PREGNANT woman who knows her unborn child has Down’s syndrome might one day be able to prevent some symptoms before giving birth.
That at least is the hope raised by experiments in mice. When fetal mouse pups that had a syndrome similar to Down’s were treated with nerve-protecting chemicals, some of the developmental delays that are part of the condition were removed.
Children with Down’s have an extra copy of chromosome 21, while mice engineered to have a similar condition are given an extra copy of a segment of chromosome 16. In both species, the development of certain motor and sensory abilities is delayed. These “trisomic” individuals may also have learning difficulties and symptoms of Alzheimer’s later in life.
Inhibiting the neurotransmitter GABA in trisomic mice can improve cognition and some have suggested this could be used in children. It would be even better, however, to treat Down’s before a child is born and so improve cognitive potential.
Previous studies both of people with Down’s and trisomic mice have also revealed malfunctions in glial cells – brain cells that regulate the development of neurons by releasing certain proteins. The aberrant cells produce less of these proteins than normal. And adding segments of some of these proteins – known as NAP and SAL – to cultured neurons from people with Down’s, which would otherwise degenerate, seems to protect the neurons (Current Pharmaceutical Design, DOI: 10.2174/138161207780618957).
Armed with this knowledge, Catherine Spong and colleagues at the National Institutes of Health in Bethesda, Maryland, injected NAP and SAL into mice pregnant with trisomic pups in the middle of their pregnancy. When the pups were born, they reached developmental milestones such as grasping a rod, righting themselves and responding to tactile stimulation at the same time as normal mice (Obstetrics and Gynecology, vol 112, p 1242). “We were able to prevent a significant amount of the delay,” says Spong.
When the pups were born, they reached developmental milestones at the same time as normal mice
The brains of the treated mice also showed normal levels of ADNP – one of the regulatory proteins underproduced by Down’s-affected glial cells – and of another compound that is a marker for healthy glial cells. Both findings indicate that some effects of Down’s had been removed.
Now Spong is watching to see if mice treated as fetuses also display less of a learning deficit as they mature. She hopes that the prenatal treatment might permanently increase the expression of the proteins in question.
What works in mice or cultured human cells doesn’t always work in people, of course. Several compounds have shown promise in human cells for the treatment of Alzheimer’s but disappointed when tested in people, warns Jorge Busciglio, a neurobiologist at the University of California, Irvine, who was one of the team that treated cultured human neurons with NAP and SAL. Nonetheless he is cautiously optimistic.
Charles Cantor of the company Sequenom in San Diego, California, which is developing a non-invasive prenatal blood-screening test for Down’s (New Scientist, 11 October, p 10), is excited at the prospect of a prenatal treatment. “I’d love to see these early screening tests lead to therapy and not just termination,” he says. “It would have a big impact, especially for families that are not willing to consider abortion as an option.”
Categories: Missed - Medical Breakthroughs