NOTEBOOKN-acetylputrescine, suggesting that her
polyamine pathway had stabilized.
This quick turnaround—from diag-
nosis to administering a potential treat-
ment in roughly 16 months—is “extraor-
dinarily unusual,” says Anne Pariser, the
director of the Office of Rare Diseases
Research at the National Institutes of
Health. “There’s really only a handful of
cases like that.” She attributes the speed
to the ready availability of an off-the-shelf
drug that came with detailed dosage and
safety assessments in children, as well
as a preexisting animal model that had
responded positively to the therapy. “In
this case, they had a body of evidence that
they could rely upon.”Since Marley’s diagnosis, the number
of documented BABS cases has risen to
at least nine, including four described in a
2018 study (Am J Med Genet A, 176:2554–
60). It’s still extremely infrequent, but
according to Pariser, diagnoses of rare
diseases tend to accumulate as evidence
grows, and Bachmann also expects more to
surface. “I’m sure in five or ten years, we’ll
know of maybe forty or fifty,” he says. (He,
Bupp, and Rajasekaran are named as coin-
ventors on a patent application related to
treating disorders caused by ODC1 muta-
tions.) Researchers have already learned
a lot from the nine cases so far, includ-
ing the fact that each patient has a unique
mutation, all of which affect polyaminesynthesis in different ways. Shortly after
Marley began treatment, a seven-year-
old boy diagnosed with BABS started tak-
ing DFMO; Bupp says that his mother
has told him that her son is “getting bet-
ter every day.”
The success of the DFMO has spurred
additional research into BABS and other
rare diseases. Stewart of Johns Hopkins is
using mice and patient cell lines to inves-
tigate DFMO as a treatment for Snyder-
Robinson syndrome, another polyamine
disorder. And Kwame Anyane-Yeboa, a
geneticist at Columbia University Medical
Center, is testing turmeric in an 18-year-old
BABS patient. One of the spice’s ingredi-
ents, curcumin, has been reported to reduce
ODC activity in certain cell lines, although
there are no data about its effectiveness in
people. “If we could treat this [condition]
through diet, that would probably be easier
for parents and other people to use,” Any-
ane-Yeboa tells The Scientist. He adds that
while his patient has grown some hair since
starting a dietary regimen of one teaspoon
of turmeric per meal almost a year ago, “the
question in our minds is whether the neu-
rological part is reversible or not.”
For Marley’s part, she’s busy playing
catch-up. On a video call with The Scien-
tist in August, Marley, now six years old,
sat on her mother’s lap, smiling and crying
in equal measure. This, her mother says, is
something the family is still adjusting to.
Marley is now more than a year into her
treatment—which will continue indefi-
nitely. And while her quality of life has
undoubtedly improved, the changes have
also brought new behavioral problems.
Even so, her daughter’s journey “is my
favorite story in life,” Berthoud says. “There
are so many patients out there with undiag-
nosed diseases that this doesn’t happen to,
and when I look back at how quickly it hap-
pened, it’s absolutely amazing that every-
thing lined up.”
—Amanda Heidt22 THE SCIENTIST | the-scientist.com
TAYLOR BALLEK, SPECTRUM HEALTH BEATTURN AROUND: Marley, whose doctors
identified a genetic mutation underlying her
condition and repurposed a drug to treat it within
just two years, with her family in 2018 (above) and
with her physician Caleb Bupp in 2021 (below)