by LOREN DeVITO, PhD AND
RACHEL DOLHUN, MD
Using the same medicine(s) to treat everyone
with a given disease is the mainstay of modern
medicine. Nonetheless, this “one-size-fits-all”
approach doesn’t always lead to outcomes patients
want, as people often respond differently to the
same medicine, and some may not respond at all.
Researchers are working to address this challenge
through “precision medicine.”
In 1997, a mutation in the alpha-synuclein gene
was first linked to a family with Parkinson’s.
Though the mutation is extremely rare, alpha-
synuclein protein clumps (Lewy bodies) are seen
in the brains of nearly everyone with Parkinson’s,
and offer a potential target for slowing or
stopping disease progression.
To date, five anti-alpha-synuclein therapies
have advanced through drug development to
arrive in clinical (human) testing. Other genetic
mutations also are leading to treatments. LRRK2,
although fairly uncommon, is the greatest known
genetic contributor to PD and has inspired
the development of LRRK2 inhibitor drugs
expected to enter clinical trials within 18 months.
Additionally, medications targeting GBA, the
most common of the currently known PD genetic
mutations, have made it into clinical testing.
These are all examples of precision medicine.
Precision medicine involves tailoring therapies for
individuals based on their genes, environment and/
or lifestyle. You may be familiar with this approach
for cancer — unlike chemotherapy that kills cancer
(and healthy) cells, successful personalized drugs
instead target genetic mutations. But how might
precision medicine be used to treat Parkinson’s
Parkinson’s is a heterogeneous disorder, meaning
no two individuals have the same symptoms,
disease course or treatment response. If we could
better understand what drives these differences,
we could, in theory, develop better medicine.
“We will only get to true cures if we can move
away from historical clinical disease definitions
to one more nuanced and linked to underlying
biology, genetics and pathology,” said MJFF
CEO Todd Sherer, PhD and co-authors in
Personalized Medicine. “Truly transforming PD
treatment into a precision approach will require
tackling key research and regulatory challenges
and the coordinated effort of the entire PD
As i n cancer, some Parkinson’s scientists believe
genetic mutations may be the basis for tailored
treatments. Even though known mutations account
for fewer than 10 percent of total PD cases, a greater
understanding of Parkinson’s genetics already has
led to critical discoveries believed to be applicable
to all individuals with the disease. “Finding a
common mechanism behind different suspected
causes of Parkinson’s suggests that there might also
be a common means to treat or cure it,” says Marco
Baptista, PhD, director of research programs at
The Michael J. Fox Foundation (MJFF).
Learn more about Parkinson’s genetics at