Study Demonstrates Potential Method for Treating Congenital Diseases In Utero

Print 20 October 2016
Caroline Hroncich / BioPharm International

A team of researchers have demonstrated a potential method for treating congenital diseases in utero. In a new study published on Sept. 28, 2016 inNucleic Acids Research, scientists from Rosalind Franklin University of Medicine and Oregon Health & Science University demonstrate the drug delivery of antisense oligonucleotides (ASOs) to amniotic fluid in utero to treat genetic defects in mice.

The World Health Organization estimates that worldwide approximately 303,000 newborns die four weeks after birth from congenital anomalies. Congenital anomalies contribute to long-term disability, and it can be difficult to pinpoint the exact cause of these defects. “The best way to treat a disease that we know will emerge at birth is to deliver a therapy in utero to the developing fetus before irreparable damage occurs,” John Brigande, PhD, principal investigator in the Oregon Hearing Research Center said in a statement.

Delivering therapies during pregnancy can be challenging because scientists must regulate risks to both the mother and child. ASOs are favored for treating genetic diseases because they have good pharmacologic, pharmacokinetic, and toxicological properties, the researchers say. However, the safety and efficacy of ASOs in utero is not known. Some stem-cell and gene therapies are currently being examined for use in utero, the study notes, but using pharmacologic agents, such as ASOs, have not been investigated.

In this study, scientists use the metastasis associated lung adenocarcinoma transcript 1 (MALAT1) to determine if ASOs can target gene expression in the amniotic cavity. Researchers injected ASOs into the amniotic cavity of mice at embryonic day 13–13.5 and then assessed “ASO distribution and MALATIRNA expression after birth.” The scientists found that the injection of ASOs did have an effect on RNA transcription in the liver, kidney, and inner ear of the mice after birth. The researchers suggest that “intra-amniotic cavity injection of ASOs represents a relatively non-invasive modality for the treatment of congenital disease or other conditions that adversely affect fetal growth and development.” Although more research is needed, this method could potentially be used to alter aberrant gene expressions in utero.

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