Positron Emission Tomography (PET) Imaging in People With Gaucher Mutations

Conditions:Parkinsons Disease, Metabolic
Therapuetic Areas:Neurology, Pharmacology / Toxicology
Age Range:21 - 100
Start Date:March 10, 2006

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Functional Imaging in Subjects With Glucocerebrosidase Mutations

This study will use positron emission tomography (PET) to compare how people with Gaucher
disease or Gaucher disease carriers with parkinsonism, and their family members, use dopamine
in their brains in comparison with healthy normal volunteers and people who have Parkinson
disease. PET assesses organ function by measuring metabolism. In this study, magnetic
resonance imaging (MRI) is used in conjunction with PET to help better interpret and
understand the information gleaned from PET.

People 21 years of age and older with the following conditions may be eligible for this

- Gaucher disease and parkinsonism

- Parkinsonism and a family history of Gaucher disease

- Gaucher disease and a family history of parkinsonism

- Gaucher disease carriers who have parkinsonism or a family history of parkinsonism

- Unaffected people with a family history of Gaucher disease and parkinsonism

- Healthy volunteers

Participants undergo the following tests and procedures:

- Personal and family medical history

- Physical examination

- PET scan: The subject lies on a table that slides into the PET scanner until his or her
head is positioned properly in the scanner. A catheter is inserted into a vein. An
initial scan is done to obtain images before radionuclides are injected. Radioactive
water is then injected through the catheter and the subject is asked questions in order
to stimulate blood flow in certain areas of the brain to show what parts of the brain
are activated. Fluorodopa is then infused through the catheter over 3 minutes. The PET
scan can last up to 2 hours.

- MRI scan: This test uses a magnetic field and radio waves to obtain images of organs.
The subject lies still on a bed in the middle of a circular scanner for about 30

An association between Gaucher disease and parkinsonism has been demonstrated by the
concurrence of parkinsonian manifestations in patients with Gaucher disease and an increased
incidence of glucocerebrosidase (GBA) mutations in subjects with parkinsonism of various
ethnicities. Furthermore, there is a significant number of obligate and confirmed Gaucher
carriers with parkinsonian manifestations. Thus, alterations in GBA appear to be a more
common risk factor than previously thought for the development of sporadic Parkinson disease
and related disorders. However, in affected and at-risk individuals, the identification and
characterization of early parkinsonian manifestations, and the rate of progression of
symptoms have not been studied objectively. We propose an in-vivo study that will employ
multiple imaging modalities to better define the phenotype in GBA-associated parkinsonism,
follow disease progression, and identify at-risk individuals. The subjects include patients
with Gaucher disease and Gaucher carriers with parkinsonian manifestations, and clinically
unaffected but at-risk individuals carrying GBA mutations, and have/ a first degree relative
with parkinsonism. The control groups consist of individuals with Gaucher disease but no
parkinsonian symptoms, relatives of probands without GBA mutations, PD patients without GBA
mutations, and healthy volunteers. Positron emission tomography (PET) with 6-[F-18]
Fluoro-L-Dopa (6FD) will be used to evaluate presynaptic dopaminergic function, where 6FD
uptake in putamen and striatum will be employed as a measure of neuronal structural integrity
in substantia nigra. Each subject will be screened with an MRI to rule-out anatomic brain
abnormalities, and to further delineate areas of interest in the PET scans. Subjects will
also undergo transcranial ultrasonography (TCS) to assess the substantia nigra
non-invasively. The results of both the PET scans and TCS will be kept confidential, and will
not be communicated to the individuals or families involved in the study. In addition to the
imaging studies, all patients will undergo a physical and neurological examination,
neurocognitive evaluation, and olfactory testing.


The study will include adult subjects age 21 or older carrying GBA mutations. The two major
study groups will include subjects with parkinsonism and unaffected subjedcts yet at risk
with a first degree family member with parkinsonism.

Controls will include subjects without GBA mutations, with sporadic PD and healthy
volunteers who do not have a family history of parkinsonism or Gaucher disease.

Healthy Volunteers and Control subjects will be matched for age, gender and handedness for
statistical purposes.


The subjects excluded from the study are those:

1. with severe cognitive deficits impairing decision making

2. unable or medically unsafe to withdraw from their current medications, such as
subjects on SSRIs and other psychoactive drugs.

3. pregnant or nursing. All women of child bearing potential will undergo a pregnancy

4. With a history of neurologic conditions such as stroke or any focal brain lesion that
may result in parkinsonian manifestations. Individuals with such MRI findings will be
excluded from the study.
We found this trial at
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, MD
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