Harvard Teaching Hospitals funded to develop dopamine neuron replacement treatment
Parkinson's Progression Markers Initiative making iPSCs available to broad research community
Dopamine neurons engineered from iPSCs may hold utility as therapeutics and research tools
NEW
YORK, May 25, 2016
The Michael J. Fox Foundation for
Parkinson's Research (MJFF) announced funding for two projects leveraging the
promise of engineered stem cells to speed new therapies and deeper
understanding of Parkinson's disease.
Advances
in technology are allowing scientists to engineer dopamine neurons, which
degenerate and die in Parkinson's disease, from skin and blood cells.
Researchers are attempting to use these neurons to replace what is lost in
Parkinson's and restore motor function. In addition, the cells can serve as
research tools for exploration into the disease process and impact of
therapeutic intervention.
"The
complexity and mystery of brain diseases make them incredibly difficult to
understand and to treat," says MJFF CEO Todd Sherer, PhD. "Stem cell
technologies may offer a more sophisticated dopamine replacement approach and
provide the opportunity to study the influence of disease and of interventions
on these vulnerable cells."
Therapy
Replacing Machinery, Not Only Product
Dopamine
loss causes Parkinson's motor symptoms including tremor, rigidity and slowness
and may play a role in some non-motor symptoms. Replacing dopamine neurons may
provide a regulated stream of dopamine that would alleviate motor symptoms.
The
Michael J. Fox Foundation and the National Stem Cell Foundation (NSCF) are
partnering to fund Ole Isacson, MD, director of the Neuroregeneration Research
Institute at McLean Hospital and principal faculty at Harvard Stem Cell
Institute, to further study implantation of dopamine neurons made from induced
pluripotent stem cells (iPSCs) in the brains of non-human primates. In 2015,
Dr. Isacson published that implanted iPSC-derived dopamine neurons survived and
that the therapy was associated with motor improvement. In 2010, Dr. Isacson
and colleagues published the first evidence of iPSC protocols, showing the
function of human midbrain dopamine neurons. Read more about this project from
NSCF and MJFF at http://www.nationalstemcellfoundation.org/?p=841.
"The
restoration of the dopamine supply system would be a significant step forward
in our treatment of Parkinson's disease," said Dr. Isacson. "This
project brings us closer to realizing such a therapy, though there is still
much work to be done."
MJFF
also is funding a project led by Lorenz Studer, MD, at Memorial Sloan Kettering
Cancer Center, investigating transplantation of dopamine neurons derived from
embryonic stem cells drawn from existing cell lines. Dr. Studer has received
multiple grants from the Foundation to study the potential of embryonic stem
cells to treat Parkinson's, and was part of the team that first successfully
developed dopamine neurons from human embryonic stem cells.
Tools
Lay Groundwork for Insight into Disease Process and Therapeutic Impact
In
addition to breeding a direct therapy, iPSCs are used to develop and test other
treatments. Dopamine neurons engineered from iPSCs provide an unparalleled
model to mimic the Parkinson's disease process in laboratory experiments.
Scientists can use this resource to, for example, investigate the impact of
causal factors such as genetic mutations and environmental exposures and the
pathogenic role of cellular processes including mitochondrial dysfunction and
oxidative stress. Furthermore, researchers can introduce drug compounds and
assess the impact on maintenance or restoration of dopamine function.
To
further these investigations, the MJFF-sponsored Parkinson's Progression
Markers Initiative (PPMI) is making iPSCs available at no cost to the
researcher community. PPMI is following a diverse population of people with
Parkinson's, with risk factors of the disease and control volunteers for more
than five years across 33 clinical sites. Robust clinical, imaging and
biological data from PPMI (also available to all qualified researchers)
increases the value of the study's iPSCs.
"PPMI
builds the infrastructure off which the greater research community can drive
discovery, validation and replication," said Mark Frasier, PhD, MJFF
Senior Vice President of Research Programs. "The 'disease in a dish' model
provided by iPSCs is an asset in the development and testing of new treatments,
and streamlined access to these well characterized tools will speed
progress."
The
Golub Capital iPSC PPMI Sub-study has two phases. The first — a partnership
with the New York Stem Cell Foundation (NYSCF) Research Institute funded by
Lawrence E. Golub and Karen L. Finerman, a member of the MJFF Board of
Directors — created iPSC lines and fibroblasts from skin samples of 20 people
with Parkinson's disease and five control volunteers. This extensive collection
of Parkinson's and control participant iPSCs with complementary clinical
information is now available to interested researchers at http://www.ppmi-info.org/cell-lines/.
The
second phase — funded by nationally recognized credit asset management firm
Golub Capital, led by Lawrence and David Golub, also a member of the MJFF Board
of Directors — contracts Cellular Dynamics International to make available
iPSCs derived from blood samples from 85 PPMI participants. This cohort
includes volunteers recently diagnosed with Parkinson's, those with genetic
mutations associated with the disease, people with a clinical risk factor of
hyposmia or REM sleep behavior disorder, and control volunteers. This diverse
population and number of samples will increase the scope and scale of
investigation with these resources, and those iPSCs will be available later
this year.
Cells
Reborn with New Direction
Stem
cells form a more specialized type of cell (e.g., muscle or red blood cell).
There are two natural categories of these cells: Embryonic stem cells (also
called pluripotent) are found in fertilized eggs and can become any type of
cell. Adult stem cells are found among specialized cells in a tissue or organ
and can differentiate only into the cell types found in that tissue or organ.
In the brain, regions involved in memory formation and smell function contain
pockets of adult stem cells that help those systems replace neurons. Research
to this point has shown other regions — including the substantia nigra (site of
Parkinson's degenerating dopamine neurons) — do not contain stem cells and
therefore do not renew.
In
2007, researchers realized another category. With genetic manipulation,
scientists engineered embryonic stem cells from an adult fibroblast (cell found
in connective tissue). The creation of these induced pluripotent stem cells has
transformed medical research. iPSCs are easier to access and may be the source
of a personalized therapy that the body is less likely to reject (i.e.,
dopamine neurons made from one's own blood or skin cell).
About
The Michael J. Fox Foundation for Parkinson's Research
As
the world's largest nonprofit funder of Parkinson's research, The Michael J.
Fox Foundation is dedicated to accelerating a cure for Parkinson's disease and
improved therapies for those living with the condition today. The Foundation
pursues its goals through an aggressively funded, highly targeted research
program coupled with active global engagement of scientists, Parkinson's
patients, business leaders, clinical trial participants, donors and
volunteers. In addition to funding more than $600 million in research to
date, the Foundation has fundamentally altered the trajectory of progress
toward a cure. Operating at the hub of worldwide Parkinson's research, the
Foundation forges groundbreaking collaborations with industry leaders, academic
scientists and government research funders; increases the flow of participants
into Parkinson's disease clinical trials with its online tool, Fox Trial
Finder; promotes Parkinson's awareness through high-profile advocacy, events
and outreach; and coordinates the grassroots involvement of thousands of Team
Fox members around the world.
SOURCE
The Michael J. Fox Foundation
http://www.prnewswire.com/news-releases/michael-j-fox-foundation-supports-two-engineered-stem-cell-research-projects-for-parkinsons-therapeutic-development-and-disease-investigation-300274396.html
No comments:
Post a Comment