JACKSONVILLE, Fla., and ROCHESTER, Minn., Nov 17, 2008 /PRNewswire-
USNewswire via COMTEX/ -- Mayo Clinic ( http://www.mayoclinic.org)
researchers have developed a method to reduce the production of alpha-
synuclein in the brain. Alpha-synuclein is a protein that is believed
to be central to the cause of Parkinson's disease (
http://www.mayoclinic.org/parkinsons-disease/). All patients with
Parkinson's disease have abnormal accumulations of alpha-synuclein
protein in the brain.
Additional audio and video resources, including excerpts from an
interview with Dr. Maraganore describing the research, are available
on the Mayo Clinic News Blog (
http://mcnewsblog.wordpress.com/2008/11/17/potential-new-therapy-to-
stop-progression-of-parkinsons-disease).
The new method involves the delivery of RNA interference compounds
directly to selected areas of the brain via injection. The RNA
interference compounds silence the gene that produces alpha-
synuclein, according to the Mayo researchers. The study was published
this month in Molecular Neurodegeneration.
Parkinson's disease is a progressive disorder that affects nerve
cells in the part of the brain that controls muscle movement.
Symptoms include tremor, slowed movement and rigid muscles. At least
1 million people in the U.S. are believed to have Parkinson's
disease, and 2 percent of the population can expect to develop the
disease during their lifetime.
"While our research has not yet been tested on humans, we expect that
these findings will lead to an effective treatment for slowing or
even halting the progression of Parkinson's disease," says Demetrius
Maraganore, M.D. ( http://www.mayoclinic.org/bio/10345655.html), a
Mayo Clinic neurologist.
Previous studies conducted by Dr. Maraganore and Matthew Farrer,
Ph.D., a Mayo Clinic neuroscientist, found that variations in the
alpha-synuclein gene result in increased protein production and are
sufficient to cause Parkinson's disease in some families, or
otherwise increase the risk for Parkinson's disease across
populations worldwide.
Drs. Maraganore and Farrer invented a method to treat Parkinson's
disease by reducing alpha-synuclein expression. Mayo Clinic patented
and licensed their invention to Alnylam Pharmaceuticals, Inc. Alnylam
is leading the effort to commercialize the Mayo invention using
Alnylam RNA interference compounds.
"For this study, we developed a lead compound of small interfering
RNAs," says Heather Melrose, Ph.D., a Mayo Clinic neuroscientist and
a lead author of this study. "By infusing this into the brains of
mice we were able to effectively reduce the production of alpha-
synuclein in the brain. The therapy produced gene silencing that
lasted up to three weeks after treatment, and the mice exhibited no
ill effects. These are desirable characteristics of a drug therapy
ultimately intended to treat disease in humans."
"Our next step with this research is to test the therapy in mice and
primates with experimental forms of Parkinson's disease and prove
that we are able to stop the disease progression in those animals,"
says Dr. Farrer. "We are hopeful, as preliminary studies suggest this
is possible."
"It is important to note that there are significant hurdles to this
therapy. The compound needs to be directly delivered to the brain
through a neurosurgical procedure -- it cannot be given by mouth or
injection into a vein," says Dr. Maraganore. "We envision that the
therapy would be delivered through Food and Drug Administration (FDA)-
approved devices currently used for deep brain stimulation therapy.
The deep brain stimulation would treat the existing symptoms of
Parkinson's disease, while the administration of the RNA interference
compounds might halt the progression of the disease."
Alpha-synuclein protein also accumulates abnormally in other brain
degenerations, including multiple system atrophy (MSA) (
http://www.mayoclinic.org/multiple-system-atrophy/) and dementia with
Lewy bodies ( http://www.mayoclinic.org/lewy-body-dementia/).
Therefore, Mayo researchers expect that RNA interference therapy
could be beneficial for patients with those conditions.

This study was funded in part by a grant from the Michael J. Fox
Foundation. Mayo Clinic has an agreement with Alnylam whereby Mayo
has granted Alnylam an exclusive license to certain patents and know-
how. Mayo Clinic and inventors of this intellectual property may
receive developmental milestone and/or royalty payments pursuant to
this agreement.
SOURCE Mayo Clinic

Last update: 11:56 a.m. EST Nov. 17, 2008