THE FOX FOCUS...
ON RESEARCH
With leadership from The Michael J. Fox Foundation, drug
companies put patients first in unusual collaboration.
by maggie mcguire
T
he Michael J. Fox Foundation
has united three competing
pharmaceutical companies in
a consortium to advance the
development of drugs targeting LRRK2.
Mutations in the LRRK2 gene are
the most common genetic cause of
Parkinson’s disease (PD). While genetic
cases of PD are rare, understanding the
genetics of PD can lead to treatments for
everyone with the disease. For this reason,
LRRK2 is of great interest to drugmakers,
who see the possibility for a diseasemodifying medication (a drug that could
slow or stop the progression of PD) in
so-called LRRK2 inhibitors. Researchers
hypothesize that lowering activity with
these drugs could protect brain cells from
the damage caused by PD.
With the goal of accelerating progress on
LRRK2, MJFF has established a roadmap
for studying the target and has funded $90
million in LRRK2 research to date.
A bump in the road
Every drug must overcome hurdles on
its path to market. Last January, one such
potential hurdle was identified for LRRK2
inhibitors. In a paper published in the
journal Science Translational Medicine,
authors from biotechnology company
Genentech and MJFF reported that they
had observed changes in the lung tissue
of pre-clinical models after introducing a
LRRK2 inhibitor.
“We don’t know if the changes would
have a negative effect, but any
modification is a reason to pause and to
consider the safety of the therapy for
2 THE FOX FOCUS
humans,” said Brian Fiske, PhD, MJFF vice
president of research programs and an
author on the paper. “Nonetheless, LRRK2
remains one of our top priority targets for a
therapy to stop or slow Parkinson’s.”
MJFF organizes drug development leaders
to move forward
Concerns around LRRK2 inhibitors first
came to light early in 2014. MJFF rapidly
organized a meeting with field leaders.
Because kinase inhibitors are a common
class of drugs, a handful of companies
already had compounds designed to target
LRRK2.
Strategizing to ensure the future of
LRRK2 drug development, MJFF
proposed a consortium approach to
illuminate the nature and scale of safety
issues surrounding LRRK2. Research
groups from Genentech, Merck and Pfizer
signed on to join the LRRK2 Safety
Initiative.
As members of the consortium, each
group submits a different LRRK2
inhibitor compound for independent
testing to determine if some inhibitors are
safer than others — that is, whether
changes in lung tissue varied depending on
the inhibitor used. Data on each
compound is shared across the consortium.
This is a highly unusual arrangement in the
competitive world of drug development.
But the members recognize that by
working together, they’re more efficiently
growing the field-wide understanding of
the safety and impact of LRRK2
inhibitors.
continued on page 12 ›
THE SHERER
REPORT
A NOTE FROM OUR CEO
“What should we be
aware of this Parkinson’s
Awareness Month?”
We declare it to our loved ones. We tweet
it, blog it and post it on Facebook: April is
Parkinson’s Awareness Month. But of what,
exactly, are we trying to raise awareness?
At The Michael J. Fox Foundation, we
want Parkinson’s families to be aware that
we’re making real progress on the road to
a ne