Eric Dupont,* Pierre E. Savard,†
Camille Jourdain,‡ Christina Juneau,* Alain Thibodeau,* Neil Ross,§ Kenneth
Marenus,¶ Daniel H. Maes,¶ Georges Pelletier,† and Daniel N. Sauder#
Background: A number of inflammatory and immune diseases
are associated with vascular changes. Psoriasis, as an example, is a common inflammatory
skin disease with dilation of capillaries as an early histological change. In more
developed psoriatic lesions there is proliferation of blood vessels and
neovascularization. The use of agents that target these vascular changes represents a
novel therapeutic strategy in the treatment of inflammatory diseases. Since cartilage is
an avascular tissue, it has been hypothesized that there may be factors found in cartilage
that inhibit blood vessel formation.
Objective: The objectives of this study were 1) to
determine whether extracts of cartilage could inhibit angiogenesis, and 2) since altered
angiogenesis is associated with certain diseases, including psoriasis, to examine whether
inhibition of angiogenesis could potentially contribute to the treatment of psoriasis.
Methods: Extracts of shark cartilage were prepared by
homogenization and ultrafiltration to derive the active agent termed AE-941. This agent
was tested for antiangiogenesis activity using the embryonic vascularization test, which
is a modification of the ex vivo chick embryo culture (CAM). Since one of the first steps
in angiogenesis is degradation by metalloproteinases of the basement membrane of
capillaries, AE-941 was tested for collagenase activity using a fluorogenic peptide
substrate. Anti-inflammatory properties were tested using a cutaneous irritation model in
Results: A dose dependent inhibition in embryonic
neovascularization as well as in collagenase activity by AE-941 was demonstrated. When
test compounds were applied on the forearms of test subjects, AE-941 was shown to have
anti-inflammatory properties. Anecdotal data suggested that topical AE-941 had a
beneficial effect in psoriasis.
Conclusion: Our results show that AE-941 has
anti-angiogenic and anti-inflammatory properties. Antiangiogenesis agents such as AE-941
provide an entirely new class of agents to treat cutaneous and systemic diseases
associated with altered vascularity.