in the long run when gene therapy can modify an individual’s genome precisely enough to cure them of a severe disease, earlier treatment will often be higher – and the womb is as early as possible. Last week on the annual meeting of the American Society of Gene & Cell Therapy in Los Angeles, a handful of researchers presented their advances in uterine gene therapy, showing that research in laboratory animals offers some hope for treating humans, but still faces major hurdles.
Doctors can already detect abnormalities within the DNA of a developing human fetus. Conditions like sickle cell anemia and spinal muscular atrophy arise with genetic signatures – sometimes so simple as a single gene mutation – showing up on prenatal screens. New gene therapies can treat adults and even children with these conditions, but they’ve some downsides: A single dose can cost hundreds of thousands of dollars, and plenty of are currently only available to participants in clinical trials. First of all, by the point an individual receives them, they could have already got spent months, if not years, living with a serious illness.
Doctors and scientists hope that by correcting these abnormalities before birth, the newborn may have a greater likelihood of living a healthy life. “The major advantage of using these therapies within the womb or before birth could be to stop disease before it occurs,” says Bill Peranteau, a pediatric and fetal surgeon at Children’s Hospital of Philadelphia, whose team was present on the conference.
His team studied many diseases, including cystic fibrosis and metabolic disorders. Other conference attendees presented research on conditions affecting the liver, muscles, brain or spinal cord. In general, these teams are inclined to concentrate on severe illnesses that may benefit from early treatment. For some conditions, Peranteau says, “in case you wait until birth – or long after birth – you’ll miss a chance to stop irreversible pathology.”
Fetal development offers this window because at this point the fetus has many unspecialized stem cells that can give rise to every kind of body tissue. The fetus’s immune system isn’t fully mature, so it’s less more likely to reject biological therapy than an infant’s immune system. And it’s small, which suggests its dose of a fancy, expensive drug might be small too.
A gene therapy “drug” isn’t a drug in the standard sense; it isn’t a chemical that kills invading germs or relieves symptoms of disease. Instead, it’s often a DNA-editing tool like Crispr packaged in a variety of delivery medium, often a virus or nanoparticle, that carries it to focus on cells. Therapy can then cut, swap or insert genes to reverse or ameliorate the disease.
“Delivery remains to be a really big challenge,” says Rohan Palanki, a bioengineer and PhD student who works with Peranteau, because targeting cells in organs corresponding to the brain, lungs and skin might be difficult. The best solution to take care of childbirth relies on the disease and the variety of gene therapy. Researchers can optimize the microscopic carrier that delivers the genetic machinery, inject a drug into a particular region or at a particular time in pregnancy – or the entire above.
