Establishment of Biomarkers for Fabry Disease
| Status: | Completed |
|---|---|
| Conditions: | Hematology, Metabolic |
| Therapuetic Areas: | Hematology, Pharmacology / Toxicology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/2/2016 |
| Start Date: | July 2010 |
| End Date: | December 2014 |
| Contact: | Deborah M Grzybowski, PhD |
| Email: | grzybowski.3@osu.edu |
| Phone: | 614-598-8159 |
Fabry disease, an x-linked recessive lysosomal storage disease (LSD) is commonly recognized
as a cause of renal failure in involved men and more recently recognized in women too. Women
are involved in significant numbers and with complications, as are men, of vascular disease.
This manifests as unexpected strokes in young adults. We have morphologic evidence that
storage-endotheliopathy induced microvascular disease is the cause of cardiopathy and of
cryptogenic strokes, and that storage endotheliopathy starts in early life, probably before
birth. Based on our earlier work with other endotheliopathies such as diabetes mellitus,
Susac syndrome, and hypertension, we will find and study patients using unique methods,
neuro-retinal fluorescein angiography (NRFA), that we have developed for this purpose. These
methods include NRFA to demonstrate capillary perfusion in the optic nerve head and retinal
quadrants. We anticipate, based on our earlier experience with other endotheliopathies, that
we will show more vascular pathology earlier than previously reported. Using epidemiologic
and genetic tools we will find more patients than previously known or expected. It will
offer opportunity for earlier diagnosis, prognosis, and response to enzyme replacement
therapy.
We hypothesize that Fabry disease is a poorly recognized and poorly characterized cause of
microvascular disease and cryptogenic strokes in young women and men. Neuroretinal capillary
perfusion abnormalities in Fabry disease will be predictive of equivalent vascular disease
in kidney, heart, brain and other organs, and further that it will be responsive to change
induced by enzyme replacement therapy treatment.
as a cause of renal failure in involved men and more recently recognized in women too. Women
are involved in significant numbers and with complications, as are men, of vascular disease.
This manifests as unexpected strokes in young adults. We have morphologic evidence that
storage-endotheliopathy induced microvascular disease is the cause of cardiopathy and of
cryptogenic strokes, and that storage endotheliopathy starts in early life, probably before
birth. Based on our earlier work with other endotheliopathies such as diabetes mellitus,
Susac syndrome, and hypertension, we will find and study patients using unique methods,
neuro-retinal fluorescein angiography (NRFA), that we have developed for this purpose. These
methods include NRFA to demonstrate capillary perfusion in the optic nerve head and retinal
quadrants. We anticipate, based on our earlier experience with other endotheliopathies, that
we will show more vascular pathology earlier than previously reported. Using epidemiologic
and genetic tools we will find more patients than previously known or expected. It will
offer opportunity for earlier diagnosis, prognosis, and response to enzyme replacement
therapy.
We hypothesize that Fabry disease is a poorly recognized and poorly characterized cause of
microvascular disease and cryptogenic strokes in young women and men. Neuroretinal capillary
perfusion abnormalities in Fabry disease will be predictive of equivalent vascular disease
in kidney, heart, brain and other organs, and further that it will be responsive to change
induced by enzyme replacement therapy treatment.
Specific Aims
Specific Aim 1. To demonstrate the specificity and sensitivity of the diagnostic
capabilities of a neuroretinal examination which includes slit lamp and fundoscopy, and NRFA
for the diagnosis of Fabry disease on a subject population of identified FD patients.
Specific Aim 2. To show capillary perfusion abnormalities in optic nerve and retina using
neuroretinal fluorescein angiography in patients with Fabry disease and compare these to
renal (measured by GFR).
Specific Aim 3. To show that the change in capillary perfusion studies when compared to
baseline in response to enzyme replacement therapy treatment over time, as a manifestation
of tissue burden and prognosis is a more sensitive biomarker of the extent of patient
disease than corneal keratopathy.
Specific Aim 1. To demonstrate the specificity and sensitivity of the diagnostic
capabilities of a neuroretinal examination which includes slit lamp and fundoscopy, and NRFA
for the diagnosis of Fabry disease on a subject population of identified FD patients.
Specific Aim 2. To show capillary perfusion abnormalities in optic nerve and retina using
neuroretinal fluorescein angiography in patients with Fabry disease and compare these to
renal (measured by GFR).
Specific Aim 3. To show that the change in capillary perfusion studies when compared to
baseline in response to enzyme replacement therapy treatment over time, as a manifestation
of tissue burden and prognosis is a more sensitive biomarker of the extent of patient
disease than corneal keratopathy.
Inclusion Criteria:
- Fabry patient
- evidence of angiopathy (renal, cardiac, or ocular)
- Patients above the age of 18
Exclusion Criteria:
- Patients unable or unwilling to provide written informed consent will not be
recruited
- Patients who are below the age of 18
- Patients who have not or will not be undergoing Fluorescein angiography
- Allergy to fluorescein
- Pregnant women and fetuses are exclude from the study due to risks related to
fluorescein and no direct benefit to the pregnant woman and fetus
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