Medicines into amniotic fluid may be way to treat SMA before birth
Animal models show fetuses swallow, inhale the medicines into their bodies
Injecting medicines into the amniotic fluid — the liquid that surrounds a developing fetus during pregnancy — may be a viable strategy for treating spinal muscular atrophy (SMA) before birth, according to a new study done in animal models.
“These data demonstrated that [injecting therapies into amniotic fluid] holds potential as a minimally invasive approach for prenatal treatment of SMA and possibly other severe, early-onset neurological disorders,” researchers wrote.
The study, “Intra-amniotic antisense oligonucleotide treatment improves phenotypes in preclinical models of spinal muscular atrophy,” was published in Science Translational Medicine.
Available SMA treatments approved to be administered after birth
SMA can cause problems at or even before birth. Treatments for SMA can slow or stop disease progression, but they are approved only for use in babies that have already been born and generally aren’t effective for reversing damage that may have occurred during fetal development. Since SMA can be diagnosed in a fetus during pregnancy, researchers have begun exploring whether it may be possible to administer therapies to a developing fetus to start SMA treatment.
In this study, scientists used animal models to explore the safety and efficacy of antisense oligonucleotides (ASOs) administered into the amniotic fluid as a strategy for prenatal SMA treatment. ASOs are a type of genetic medicine that bind to RNA molecules to increase the levels of functional proteins. Spinraza (nusinersen), the first approved treatment for SMA, works using an ASO.
“Children with severe forms of SMA can have irreversible damage by the time they are born, and we wanted to see how we could treat as early as possible in the least invasive way,” Tippi MacKenzie, MD, a senior author of the study at the University of California San Francisco (UCSF), said in a university news story.
The scientists found ASO therapy could be safely delivered into amniotic fluid during pregnancy in mice, and ASO treatment during pregnancy led to better outcomes for mouse pups with SMA, including better motor function, better odds of survival, and improved number of motor neurons, which are specialized nerve cells that are progressively lost in SMA. Injecting ASOs into the amniotic fluid of sheep that did not have SMA was also shown to be safe and able to deliver the therapy to the spinal cord and other organs.
The procedure for administering the ASOs was similar to amniocentesis, which is an established procedure used to collect amniotic fluid to test for genetic diseases like SMA in a developing fetus.
‘An inverse amniocentesis’
“This is sort of an inverse amniocentesis,” said Beltran Borges, MD, the study’s first author at UCSF. “Once translated to the clinic, it could be an outpatient procedure.”
In imaging studies, the researchers found that, once the ASOs were injected into amniotic fluid, the fetus would actually swallow and inhale the medicine, delivering it into their body.
“It is remarkable that you can inject something in the amniotic fluid and let it sit there, and over time a fetus swallows it or sniffs it in, and it gets to the brain and elsewhere,” Borges said. “There are likely other routes of entry as well, including through the bloodstream.”
Although these experiments were done in animal models, the positive results provide proof-of-concept for potentially testing this approach in people, but more work will be required before translating it into the clinic, the researchers said.
“With these results, we are one step closer to testing prenatally in humans an existing treatment for those diagnosed with the disease,” MacKenzie said.
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