The Michael J. Fox Foundation Annual Report 2018 Impact + Innovation | Page 39

2018 Annual Report
Ushering
Promising Genetic
Targets Forward
Genetics has changed the landscape of
Parkinson's disease (PD) research. The
Michael J. Fox Foundation (MJFF)
is directing donor-raised capital and
research efforts to transform genetic
insights into new treatments. competing powerhouse pharmaceutical companies
2018 marked a milestone moment in the history of
LRRK2, a key known contributor to PD. LRRK2 was first
linked to PD in 2004, and researchers are continuing to
work to define its role in PD, measure its activity and
develop treatments to delay or stop progression of the
disease. And today, medications against this target are
rapidly moving closer to patient hands. target forward, supporting innovative approaches to
At our annual Parkinson’s Disease Therapeutics
Conference in October 2018, Denali Therapeutics
reported positive results from the first LRRK2 drug
trial and announced it was moving the drug into trials
with patients carrying the LRRK2 mutation, as well as
with those whose Parkinson’s is not related to LRRK2.
Denali has cited our Foundation’s work in this space
as a catalyst for its momentum.
These are the trials that almost weren't. In the early
days, when preclinical findings showed LRRK2
inhibitors caused lung tissue changes, the target
nearly stalled. "This promising genetic hint to a
Parkinson's treatment looked as if it would never be
investigated. Then the Fox Foundation stepped in,"
says Matt Herper, reporter at Forbes. MJFF organized
the LRRK2 Safety Initiative (LSI) composed of
to keep the research and development moving
forward. The LSI group — MJFF, Denali, Genentech,
Merck and Pfizer — released its findings, which have
reinvigorated LRRK2 drug development. And we
expect two more companies to begin trials of LRRK2
drugs in 2019.
Today, we continue to usher this promising genetic
define LRRK2’s protein structure and investigating
links between this key target and other known related
disorders, such as inflammatory bowel disease. MJFF
and our partners are also creating and distributing
critical research tools (eight for LRRK2 in 2018, with
five more in development); enrolling more people
in studies to learn about the role and experience
of LRRK2; and testing alternative therapeutic
approaches.
Research is also advancing with other key targets we
have identified. A growing pipeline of therapeutics
aimed at preventing or removing abnormal alpha-
synuclein accumulation into Lewy bodies is in the
clinic (eight programs). Three precision therapies
against cellular dysfunction caused by GBA mutations
are in clinical trials. Initiatives testing therapies
repurposed from other diseases, such as nilotnib,
a cancer drug, are in testing. And determined
researchers are also learning more every day about
other uncovered mutations, such as PRKN and PINK1.
At MJFF, we're optimizing our shots on goal by
pursuing multiple targets and pathways to a cure.
37