From: Chambard Torkelson, Vicki L. [mailto:[log in to unmask]]

Sent: July 08, 2011 11:17
Subject: Mayo Clinic News Release: Possible Susceptibility Genes Found in
Neurodegenerative Disorder

 

July 8, 2011 

Duska Anastasijevic 
904-953-2299 (days) 
904-953-2000 (evenings) 
[log in to unmask] 

Possible Susceptibility Genes Found in Neurodegenerative Disorder 

JACKSONVILLE, Florida -- An international research team, co-led by
scientists at Mayo Clinic <http://www.mayoclinic.org/jacksonville/> ’s
campus in Florida, has discovered three potential susceptibility genes for
development of progressive supranuclear palsy
<http://www.mayoclinic.org/progressive-supranuclear-palsy/>  (PSP), a rare
neurodegenerative disease that causes symptoms similar to those of Parkinson
<http://www.mayoclinic.org/parkinsons-disease/> ’s disease but is resistant
to Parkinson’s medications. Their report has been published online in Nature
Genetics.

The findings provide a “testable translational hypothesis” as to the
development and progression of PSP and may also provide clues into other
more common brain disorders brought about by accumulation of tau protein in
the brain, researchers say. Those “tauopathies” include some forms of
Parkinson’s disease, frontotemporal dementia, Alzheimer
<http://www.mayoclinic.org/alzheimers-disease/> ’s disease, and other
disorders.

“These are promising gene candidates that may help us understand and
potentially treat PSP,” says neuropathologist Dennis W. Dickson, M.D.
<http://mayoresearch.mayo.edu/mayo/research/staff/dickson_dw.cfm> , a study
co-lead author. “While these findings are surprisingly robust, we are still
at the very earliest stages of this work. These are excellent candidate
genes, but we have to make sure they are true susceptibility genes.”

With 29 institutions represented from the United States and Europe, the
study is one of the largest international collaborations to date researching
PSP, Dr. Dickson says. It is also one of the largest reports on a
pathologically confirmed neurological disorder.

Mayo Clinic’s contribution was pivotal, he says. With its focus on movement
disorders, Mayo Clinic in Florida is a national center for referral of
patients with PSP for diagnosis, treatment, and research. It also has the
world’s largest collection of brain tissue from PSP patients. The
10-year-old Society for Progressive Supranuclear Palsy Brain Bank,
established by Dr. Dickson, contains tissue samples from more than 800
patients with PSP. Medical institutions around the country routinely send
autopsy tissues to the Mayo PSP brain bank.

Mayo Clinic contributed over 600 of the 1,114 PSP DNA samples used in the
first half of the study; the other international institutions contributed
the rest. 

To search for susceptibility genes, the research team conducted a
genome-wide association study (GWAS), which examines the differences between
the genomes of patients with a certain disease compared to a control group
of participants without the disease. This is done by looking at single
nucleotide polymorphisms (SNPs, pronounced snips), which are DNA sequence
variations that can occur in genes or in the non-coding regions between
genes.

Researchers first assessed association between genotypes at 531,451 SNPs in
the group of 1,114 PSP DNA samples, and in blood from a control group of
3,247 participants who did not have PSP. The SNPs “hits” they found were
then tested in a second group: blood samples from 1,051 living PSP patients
and blood from a second group of 3,560 control participants. For that phase
of the study, Mayo Clinic in Florida contributed blood from about 200 PSP
patients.

In addition to finding that PSP patients had variants in their tau gene,
which was expected, the researchers also found the three SNPs that appear to
be candidate PSP genes. All three have neurological functions. MOBP is a
protein associated with myelin, an insulating material that forms a sheath
around the axon of nerves. Glial cells form myelin, and these cells are
affected in PSP. STX6 is a gene involved in recycling the membrane of a
neuron, and membrane recycling has been implicated in a number of
neurodegenerative diseases, including Alzheimer’s, according to Dr. Dickson.
The third gene, EIF2AK3, is involved in translating RNA to protein, and it
signals cells to stop making proteins when abnormal proteins start to
accumulate inside cells -- as they do in neurons when tau errantly builds
up. 

Variants in these three genes were also found in the two control
populations, but were significantly higher in the PSP patients (both brain
samples and PSP blood samples). That suggests these genes do not cause PSP,
but contribute to a person’s susceptibility to the disease, he says.

“We don’t know for sure that these SNPs are precisely at these gene
locations,” says Dr. Dickson. “If they are real PSP susceptibility genes, we
can then zero in on variants that have an impact on the disease, which might
then be exploited therapeutically.

“While we are a long way from any new treatment, this new research is
exciting for researchers who are dedicated to understanding this tragic
disorder.”

PSP affects up to 50,000 people in the United States at any given time. It
is one-tenth as common as Parkinson’s disease.

Also working on this study were neurologists Zbigniew Wszolek, M.D.
<http://mayoresearch.mayo.edu/mayo/research/staff/wszolek_zk.cfm> , and Ryan
Uitti, M.D. <http://mayoresearch.mayo.edu/mayo/research/staff/uitti_hw.cfm>
, from Mayo Clinic in Florida. The study’s co-lead authors are at
Philipps-Universität, Marburg, Germany; the University of Pittsburgh School
of Medicine; the Children’s Hospital of Philadelphia;
Justus-Liebig-Universität in Giessen, Germany; and the University of
Pennsylvania School of Medicine.

The study was funded by CurePSP/The Society for Progressive Supranuclear
Palsy. The Mayo Clinic authors declare no conflicts of interest.

### 

About Mayo Clinic 
Mayo Clinic is a nonprofit worldwide leader in medical care, research and
education for people from all walks of life. For more information, visit
www.mayoclinic.org/about/ and www.mayoclinic.org/news
<http://www.mayoclinic.org/news-florida> .

 


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