this slowdown could be minimized if the mother were given
the appropriate drug as soon as a diagnosis was made. “You
want to address the problem as early as it can be detected,”
says Tarik Haydar, who runs the Laboratory of Neural Development and Intellectual Disorders at Boston University and
collaborates with Bianchi.
Neurogenesis—the creation of neurons—occurs largely in
the womb. Between birth and puberty, neurons mature and
go through a process of myelination, or insulation, and formation of synapses, or connections. Neurogenesis continues too,
but at a snail’s pace compared with the rapid-fire production
in the womb, where—on average—300 million neurons are
created per day in early pregnancy. “There is still something
you can do after birth, but if you really hope to rescue neurogenesis, you have to do it prenatally,” says Renata Bartesaghi,
a professor in the Department of Biomedical and Neuromotor
Sciences at the University of Bologna.
Bianchi has called this possibility “fetal personalized medicine.” Any kind of fetal medicine is still very unusual, though.
There are a few complex fetal surgeries to repair birth defects,
but only one drug, the vitamin folic acid, is taken regularly
to steer the course of prenatal development. If women have
the supplement in their bodies from conception through the
first weeks of pregnancy, their babies are protected from neural tube defects including spina bifida, a malformation of the
spinal cord. Folic acid points to the importance of timing. If
taken at the right time, it prevents a serious error in development. But no amount of folic acid will help after development
has run its course.
Bianchi began testing drugs for Down syndrome on mice
in 2011, theorizing that it might be possible to change the
brains of babies with something as simple as folic acid. Her
thinking had changed when she learned of efforts to treat
fragile X syndrome, another cause of intellectual impairment,
and as new tools to investigate development became available—including the noninvasive tests, which launched that
year. “I realized that research in neurocognition was changing
rapidly,” she says.
The physical differences in Down syndrome can be seen in
an ultrasound: more fluid accumulation at the back of the neck,
or an absent nasal bone. But one of Bianchi’s first steps was
to try to find a molecular signature of the disorder by collecting amniotic fluid from pregnant women, in order to measure
the “transcriptome” of fetal cells—a readout of which genes
are turned on or off. She found about 300 genes that behaved
differently in Down syndrome, and most of them were not on
chromosome 21. That underscored the complexity of the disease, but it also provided what Bianchi says is her key finding.
Any kind of fetal medicine
is still very unusual. Only
one drug, the vitamin folic
acid, is taken regularly to
steer the course of prenatal
Babies born with Down syndrome in the U.S.
A substantial number of pregnancies are
terminated after the diagnosis.
1970 1980 1990 2000 2010
Live births with Down syndrome
Additional births with Down syndrome if there
were no Down syndrome–related abortions