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MGH Neurogenetics DNA
Diagnostic Laboratory – Sims
We are a clinical service laboratory
offering molecular DNA diagnostic testing for neurogenetic
disorders. Some of our test protocols have been developed
directly from the Massachusetts General Hospital (MGH)
research laboratories actively working in these areas.
We maintain a close working affiliation with these laboratories
so that our technology and interpretation is the most
up-to-date. Click
here for current test offerings.
Pharmacogenetics of Antidepressant
Response – Smoller,
Perlis
This project, with Maurizio Fava,
MD (Depression Clinical and Research Program), is to
identify genes that may predict response and adverse
effects to antidepressant treatment, by examining loci
in a sample of nearly 2000 patients who participated
in the “Sequenced Treatment Alternatives to Relieve
Depression” (STAR*D) study.
Therapeutic strategies
based on splicing modification in familial dysautonomia
– Slaugenhaupt
Familial Dysautonomia (FD) is a hereditary
sensory and autonomic neuropathy caused mainly by a
mutation in the IKBKAP gene that results in aberrant
skipping of exon 20. The Slaugenhaupt group has found
that the plant cytokinin, kinetin, dramatically improves
exon 20 inclusion and increases production of IKAP protein,
focusing efforts on understanding the mechanism of action
and testing the potential efficacy using animal models
and toxicity studies, with the goal of bringing kinetin
to FD patients.
Screening for drugs in
Huntington’s disease – Gusella,
MacDonald
Huntington’s disease (HD) is
characterized by degeneration of medium-sized spiny
neurons in the striatum due to an expanded polyglutamine
tract in huntingtin. Collaborative projects screen for
compounds that alter consequences of mutant huntingtin
in striatal cells, including a huntingtin ‘conformational’
property and cellular energy phenotypes. Positive “hits”
are tested in animal models to determine whether any
may provide a route for therapeutic development in HD.
Clinical trials in NF1
by topical treatment of dermal neurofibromas
– Gusella
Neurofibromatosis 1 (NF1) is a multi-system
disorder characterized by complex tumors termed neurofibromas;
cutaneous neurofibromas (CNF), non-cutaneous neurofibromas,
and plexiform neurofibromas that can transform into
malignant peripheral nerve sheath tumors (MPSNT). With
Scott Plotkin, MD, PhD of the Department of Neurology
and the Brain Tumor Center, the Gusella lab is working
to develop clinical trials for a variety of compounds
to be tested as topical creams for efficacy against
CNF.
Improved molecular diagnosis
in neuronal ceroid lipofuscinosis and hereditary spastic
paraparesis – MacDonald,
Sims
Neuronal ceroid lipofuscinosis and
hereditary spastic paraparesis are unrelated genetically
diverse disorders. The MacDonald and Sims laboratories
are working together to identify mutations in cases
where a mutation in a known NCL or HSP gene has not
been found, with the goal of understanding the cellular
pathways that lead to disease symptoms and of providing
tests for timely clinical DNA diagnosis.
Screening for drugs in
JNCL and vLINCL – Cotman
The major forms of Neuronal Ceroid
Lipofuscinosis (NCL) feature massive loss of brain neurons
due to loss of battenin (JNCL) or linclin (vLINCL).
Utilizing genetically precise JNCL and vLINCL cerebellar
cell models, the Cotman laboratory is screening for
compounds that can be tested in vivo in NCL models,
to reveal those that may probe the disease pathways
and be developed as potential therapeutics.
Intensive Residential
Treatment of Obsessive-Compulsive Disorder –
Stewart
Obsessive-Compulsive Disorder (OCD)
is clinically managed using pharmacotherapy as well
as behavior therapy. With Dr. Michael Jenike and the
OCD Institute at McLean Hospital, a study is underway
to establish the long-term efficacy of Intensive Residential
Treatment of OCD.
Improving Outcomes in
the Pharmacotherapy of Social Anxiety Disorder
– Smoller
Established treatments for social
anxiety disorder (social phobia) include antidepressant
and anxiolytic medications and cognitive-behavioral
therapies but variations in pharmacodynamically-relevant
genes may influence the effectiveness and tolerability
of antidepressant medications. With Mark Pollack, MD
(MGH Anxiety Disorders Program), Murray Stein, MD, MPH
(UC San Diego) and Michael Van Ameringen, MD (McMaster
University), the Smoller laboratory is examining genetic
predictors of response to pharmacotherapy for social
anxiety disorder.
Clinical trials for the
prevention and treatment of stroke – Rosand
In collaboration with our colleagues
in Vascular and Critical Care Neurology, we conduct
a wide range of studies of novel treatments for stroke.
Our ongoing clinical trials include those based in the
emergency department that aim to reduce the immediate
damage caused by strokes and those based in the outpatient
department that aim to prevent stroke from developing
in the first place.
Genome-wide association
study of QT interval duration – Newton-Cheh
In collaboration with investigators
at the Framingham Heart Study, the Rotterdam Study and
the Cardiovascular Health Study, Dr. Newton-Cheh is
identifying genetic variants in known and novel genes
that influence QT interval duration in the general population
and testing these variants for their influence on risk
of sudden cardiac death as a side effect of medications.
Genome-wide association
study of blood pressure: GLOBAL BPGEN –
Newton-Cheh
In a multinational collaboration with
investigators from Canada, Estonia, Finland, France,
Germany, Italy, Sweden, the United Kingdom and the United
States, the GLOBAL BPGEN consortium, in which Dr. Newton-Cheh
participates actively, seeks to identify genetic variants
in known and novel genes that influence blood pressure
in the general population and which may modulate response
to blood pressure medications.
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