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Pelizaeus-Merzbacher disease research project
Dear parents, patients, and
relatives:
We are writing to tell you about a research study on
Pelizaeus-Merzbacher disease (PMD) that is taking place at Wayne State
University. The title of the study is "Molecular Mechanism of
Neurodegenerative Diseases (Pelizaeus-Merzbacher Disease". The
overall
purpose of this research study is to increase our understanding of how
nerve cells and their parts are affected by PMD. We hope this
information will help us to identify potential therapies and treatment
options for this condition, as well as possibly other diseases that
cause nerves to break down (neurodegenerative diseases). Many
researchers Wayne State will be involved in this project, including
Drs. Alex Gow, James Garbern, John Kamholz, and Mike Shy.
One aspect of the project will be to study specifically how the genetic
mutations in PMD cause the different clinical symptoms of the
disease. We already know that mutations within the proteolipid
protein gene (PLP1) located on
the X chromosome lead to PMD and that there are different degrees of
severity of the condition. We also know that there are three
different types of genetic mutations that occur in the PLP1 gene that
can cause PMD: point mutations (small changes in the gene) that lead to
abnormal PLP1 protein, point mutations that lead to absent PLP1
protein,
and duplications, which lead to too much PLP1 protein. What we do not
know is how each of these different mutations changes the nerve cells
and causes the PMD. Nor do we know how different changes in the
gene cause different degrees of disease severity. These are two
of the questions we would like to try to answer through our research.
PMD affects the formation of the myelin sheath, the fat and protein
covering on neural fibers in the central nervous system (CNS), the
brain and spinal cord. The myelin sheath acts as an insulator of neural
fibers, allowing nerve impulses to travel down a nerve, much like the
coating you find on electrical cords. About 75% of myelin in the
central nervous system is made up of fats and cholesterol and the
remaining 25% is protein. PLP1 constitutes about half of the
protein of CNS myelin. Too much PLP1, as in what happens with a
duplication (extra copy) of the gene, is harmful to the cells that make
myelin (oligodendrocytes). Point mutations may cause the protein
to fold into the incorrect shape, and prevent it from interacting with
other molecules. Another aspect of the study will look at how the
misshapen or extra PLP1 is harmful to oligodendrocytes.
Finally, we know that in addition to problems with the central nervous
system, some people with PMD also have problem with the peripheral
nervous system (the system that supplies nerve impulses to areas of the
body like the arms and legs). We would like to know if the
problems that PLP1 mutations
cause in the myelin of the central nervous system are the same as or
different than the problems they cause in the myelin of the peripheral
nervous system. Answering this question may help us determine whether
the severity of PMD in the CNS is expected to be similar or different
to the severity in the peripheral nervous system.
We hope that by studying PMD at the cellular level (looking at how PLP1
affects what is happening in nerve cells) and at the clinical level
(evaluating the symptoms of people with PMD), this research will help
us understand how PLP1
mutations cause the various symptoms of PMD. Until we can
understand what is going wrong in the cells, leading to the symptoms,
we cannot begin to understand how to fix the symptoms.
We would like to evaluate a large number of families, at least 10 per
year over the next 5 years, in order to better determine how the
mutations on the PLP1 gene
affect the disease. Participants will be asked to do the following:
- Travel to Detroit for a two-day study
visit. We will arrange and pay for your travel costs.
Once in Detroit, participants will be asked to have the following:
- Have a physical examination and
comprehensive neurological examination. As part of these
examinations, we will collect personal medical history and family
medical history. Participants are asked to review and/or complete the
questionnaires in this packet in preparation for the questions that
will be asked about the personal and family medical histories.
They are also asked to sign a medical record release so that we can
review their medical records pertaining to the diagnosis of
PMD. Have an MRI and MRS (magnetic resonance imaging
and magnetic resonance spectroscopy).
- Have clinical electrophysiological
testing.
- OPTIONAL. Have a sural nerve biopsy.
- OPTIONAL. Have a skin biopsy.
- OPTIONAL. Consent to have the physical
and neurological examination videotaped.
More details about each of these procedures, their potential risks, and
why they are being requested is included in the enclosed informed
consent document.
If you are interested in learning more about our PMD study, please
contact us by telephone or fill out and send us the enclosed
postcard. Once we receive the postcard, we will contact you by a
phone. Please understand that this form is NOT legally binding
and you may change your mind at any time. If we do not hear from you
within two weeks of mailing our information packet, we will call you to
see if you have any questions. Participation in this study is
voluntary. Your decision not to participate will not in affect
your future health care at the Detroit Medical Center/Wayne State. If
you do not want us to call you, please check the appropriate box on the
post card and send it back to us.
If you have any questions about our study, please contact Dr. Garbern
at (313) 577-1689. For more information about PMD, contact Dr.
Garbern or visit our website.
Sincerely,
James Garbern, MD, PhD
Alexander Gow,
PhD
Co-Investigator
Principal Investigator
Back to Neurology Clinics List
Edited April 4, 2005
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