The goal of this project is to assess the efficacy of magnesium oxide on the reversal of elastic fiber calcification and clinical lesions of PXE. To achieve this goal, this proposal outlines three specific aims. (1) The primary endpoint is to assess the reversal of elastic fiber calcification through skin biopsies. A blinded dermatopathologist will grade skin biopsies on the density of Von Kossa staining. The amount of calcification of elastic fibers will be determined by assessing von Kossa staining per unit area of dermis. (2) The secondary endpoint is to assess the reversal of clinical skin lesions through investigator evaluation and clinical photographs. (3) The final aim is to assess the rate of disease progression through ophthalmologic examinations. The study consists of two parts. The first part is a year-long, double-blind, placebo-controlled study. Part two is an open-label, year-long study. In Part 1, qualified subjects will be randomized to receive either magnesium oxide supplements, or placebo, in a 1:1 ratio for the first 12 months. The starting dose will be 1000 mg daily, and depending on tolerability, doses will be decreased. Baseline evaluations will be comprised of blood chemistry panel, serum magnesium, calcium and phosphorus levels, complete blood count testing, urinalysis, clinical evaluations, punch biopsy of target lesion, ophthalmologic evaluations, photographs of skin lesions, electrocardiogram, and bone densitometry. Upon completion of the first year, barring any safety concerns, all subjects will be administered magnesium supplements for up to one additional year. The same evaluations/procedures will be conducted during Part 2.

Public Health Relevance

Pseudoxanthoma elasticum (PXE) is a systemic connective tissue disorder involving elastic tissue calcification affecting the skin, ocular system (often leading to retinal bleeding and loss of vision), and cardiovascular system (accelerated heart disease, cardiac valvular disease, claudication, and gastrointestinal bleeding as a result of calcification in the arteries).1 Finding a modality of therapy that may reduce this calcification would be a substantial contribution to the clinical management of these patients and would ultimately improve their quality of life.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01FD003903-03
Application #
8709818
Study Section
Special Emphasis Panel (ZFD1)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Dermatology
Type
Schools of Medicine
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10029