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ILLUSTRATION BY ALEXIS BEAUCLAIR. DATA: SYMPHONY HEALTH◼ SOLUTIONS Bloomberg Businessweek July 22, 2019is exploring whether a new type of experimental cancer
drug, MNK inhibitors, could stop chronic pain by prevent-
ing neurons from sending a constant flow of “it hurts”
signals even when a stimulus is no longer present.
A third startup, EicOsis, is an example of almost ser-
endipitous research. It was founded by Bruce Hammock,
a University of California at Davis entomology professor
who’s spent five decades researching an enzyme that
helps insects metabolize the hormones they need for
metamorphosis.WorkingwithAlonsoGuedes,anasso-
ciateprofessorofveterinaryanesthesia and pain med-
icine at the University of Minnesota, Hammock noticed
that the enzyme, helpful to bugs, might prove harmful
to mammals. The two began to test the idea that block-
ing the enzyme might have an impact on pain in horses.
The breakthrough came when Hammock and
Guedes were called to the stall of Hulahalla, a 4-year-
oldmarewithhorseracingroyaltyinherbloodline—
hergreat-grandfather was Triple Crown winner Seattle
Slew—who’d suddenly been immobilized with a hoof
inflammation disorder called laminitis. When UC Davis
caretakers decided the only humane course of action
would be to euthanize Hulahalla, Guedes asked to try the
compound they’d developed. That same day, the horse
was back on her feet.
Some in the scientific establishment ridiculed the
idea that tests on horses and pets could be relevant to
people, Hammock says. But after a series of academic
papers showed similar results, EicOsis raised enough
government grant money to move into human trials.
“For those of us in academia, there was basically no
way to get from an idea to a drug,” says Robert Gereau,
directoroftheWashingtonUniversityPainCenterin
St.Louis. “There’s a lot happening right now. There’s a
lot of innovation in drug discovery happening in academia
that’s being spun out into small companies.” Neurolux,
which emerged from NIH-funded research, sells a wire-
lessly controlled research tool that can be implanted into
the brains of genetically modified mice. Animals fitted
with the device have glowing red or blue dots on their
heads, and researchers can use the light to control their
neural circuits—essentially, to flip the pain pathways in
their brains off and on during experiments.
The long-term goal is to show if it’s possible to use the
technique, called optogenetics, to relieve pain, Gereau
says.Thatwouldmeanusinggenetherapytointroduce
a light-sensitive protein from a different source, such
as algae, into the neurons of the brain and spinal cord.
Researchers might then essentially use light to “hack
into neural circuits and control their activity at will” and
stop them from transmitting pain signals, Gereau says.
First, his lab must show the device can work in animals
bigger than mice.
Others are pushing the limits of manipulating humanThepaininSusanHahla’sfeetstartedaspinsand
needles, then progressed to flickering fires. Each month,
Hahla found herself in a different doctor’s office, waiting
for another disease to be crossed off the list: no rest-
lesslegsyndrome,norheumatism,andno,thankgood-
ness,multiplesclerosis.
Finally, doctors at Oslo
University Hospital in Norway
diagnosed her with small-fiber
neuropathy, a disorder caused
when nerves misfire. “It gave
me a good feeling that I wasn’t
dreaming up something,” says
Hahla, 71. But finding a treatment
proved elusive. Some drugs had
no effect on the pain; one, usu-
ally prescribed for epilepsy, left
her forgetful and unable to walk
a straight line.
After suffering for more than
a decade, Hahla agreed to
become the only subject in an
unusual test. A team of German
scientists took a sample of cells
from her skin, then, in a delicate, monthslong process,
reprogrammed them into a type of stem cell, then into
nerve cells. Using tiny electrical shocks, they found a
drug—normally prescribed for people with seizures—that
seemed to block the pain signals at the cellular level.
Within five days of using it, she was almost pain-free.
Hahla’s experience is illustrative of a more targeted
approach to treating pain. In the wake of the opioid cri-
sis, politicians and doctors alike have called for a substi-
tute for the narcotics once wielded against all sorts of
pain.Theneedis acute:Some400,000peoplediedof
opioid overdoses from 1999 to 2017 in the U.S., accord-
ing to the Centers for Disease Control and Prevention.
But a recent crop of opioid replacements from big phar-
maceutical companies has been underwhelming. The
NationalInstitutesofHealthlastyearalmostdoubled
funding,to$1.1billion, for research into opioid alterna-
tives through a program called the HEAL (Helping to End
Addiction Long-term) Initiative. “If we could replace the
entire opioid pharmacopoeia, I think everybody would be
really happy,” says Ted Price, a neuroscience professor
who directs the newly formed Center for Advanced Pain
Studies at the University of Texas at Dallas.
The treatments may take decades to develop, but
scientists are inching closer as a bevy of smaller play-
ers research solutions from RNA sequencing to prod-
ucts adapted from snail venom and hot peppers. Price
is advising one startup that’s launching its first human
trial of a compound that aims to replace opioids for
immediate and long-term pain. Another he co-foundedOxycodone HCL and
oxycodone HCL/
acetaminophen
prescriptions in the U.S.Q1’09 Q2 ’19111315m