Novel gene therapy approach: inducing self-repair

9/5/06. By the Public Health Genetics Unit

Prospects for a new form of gene therapy have been presented at the European Society of Human Genetics conference in Amsterdam.

Researchers from the University of Cologne Institute for Genetics are not taking the usual approach to gene therapy: attempting to insert functional copies of a defective gene into cells. Instead, they are testing whether a drug can be used to enhance innate genetic compensatory mechanisms to correct the cellular defect.

They investigated the effects of an epilepsy drug called valproate in patients with spinal muscular atrophy (SMA), a relatively common inherited disease. Affected individuals lack a copy of the SMN1 gene; a second gene, SMN2, produces the same gene product (survival motor neuron protein, SMN) but at much lower levels. The severity of disease is decreased when there are additional copies of the SMN2 gene present, increasing overall SMN production. Valproate was found to raise SMN levels, and in 20 spinal muscular atrophy patients who received the drug, seven showed increased levels of SMN in their blood.

Unfortunately, at this stage it is not clear whether or not the increased protein levels were the result of SMN2 gene expression specifically in motor neurons, which is where it is required for a therapeutic effect. However, researchers are optimistic; Professor Brunhilde Wirth said: "The long-term outcome could be both improved therapy to enable a better quality of life for SMA patients, and also the introduction of neonatal screening so that therapy could be started before the first symptoms appear." (See Self-repair gene therapy promise , BBC news report: 7 May 2006.)

Dr Fred Kavalier, of the British Society for Human Genetics , commented: "This work shows that it may be possible to influence the behaviour of genes with drugs."

Background: Gene therapy