Researchers at Washington University School of Medicine in St. Louis claim that they have achieved a significant success in preventing deadly genetic disease before birth in zebrafish.
The researchers say that injecting a customized "genetic patch" into early stage fish embryos enabled them to correct a genetic mutation, so that the embryos would develop normally.
Describing their study in a report, the researchers said that their work might lead to the prevention of up to one-fifth of birth defects in humans caused by genetic mutations, for zebrafish are vertebrates that develop similarly to humans.
The groundbreaking discovery is a result of the efforts of Erik C. Madsen, an M.D. student in the Medical Scientist Training Program at Washington University School of Medicine, who used a zebrafish model of Menkes disease — an inherited disorder of copper metabolism caused by a mutation in the human version of the ATP7A gene.
Children with Menkes disease have seizures, extensive neurodegeneration in the gray matter of the brain, abnormal bone development and kinky, colourless hair. Most children with Menkes die before age 10, and treatment with copper is largely ineffective.
The development of organs in the foetus is nearly complete at a very early stage, and by that time, the mutation causing Menkes disease has already affected brain and nerve development.
The researchers wanted to know whether they could prevent the Menkes-like disease in zebrafish by correcting genetic mutations that impair copper metabolism, during the brief period in which organs develop.
They used zebrafish with two different mutations in the ATP7A gene, resulting in a disease in the fish that has many of the same characteristics of the human Menkes disease.
Madsen, who conducted the research with another M.D. student named Bryce Mendelsohn, designed a specific therapy to correct each mutation with morpholinos, synthetic molecules that modify gene expression.
The researcher duo injected the zebrafish embryos with the customized therapy during the critical window of development, and found that the fish hatched and grew without any discernable defects.
"This method of copper delivery suggests that the prevention of the neurodegenerative features in Menkes disease in children may be possible with therapeutic interventions that correct the genetic defect within a specific developmental window," Madsen said.
The genetic mutations Madsen's team worked with are caused by an interruption in genetic code, also known as splicing defects. The morpholinos prevent that interruption by patching over the defect so the gene can generate its normal product.
"Consider the genetic code as a book, and someone has put in random letters or gibberish in the middle of the book. To be able to read the book, you have to ignore the gibberish. If we can make cells ignore the gibberish, or the splicing defect, the fetus can develop normally," Madsen said.
The researchers say that, since about 20 per cent of genetic diseases are caused by splicing defects, their treatment method may potentially be used for many other genetic diseases.
They also describe their work, published in the Proceedings of the National Academy of Sciences' advance online edition, as an important step towards personalized medicine, which can tailor treatment to an individual's genetic makeup.