Hyaluronan (HA) is an important
component of skin, cartilage, and connective tissue. It is actively
synthesized during wound heating and tissue repair to provide a
framework for ingrowth of blood vessels and fibroblasts. Changes
in the serum and tissue concentrations of hyaluronan are associated
with inflammatory and degenerative arthropathies such as rheumatoid
arthritis. Tissue augmentation and treatment of wrinkles and related
anomalies has become an increasing problem for dermatologists and
there is an ever increasing market for these therapies. Hyaluronan
is a component of the family of glycoaminoglycans (GAGS, substances
known for their property of retaining water), that significantly
decreases with aging and in wrinkles. HA is synthesized at the plasma
membrane and extruded through a putative membrane pore directly
into the extracellular space by hyaluronan synthase. This enzyme
is membrane anchored and polymerizes UDP sugars into high molecular
weight hyaluronan. In addition to genes found in bacteria and other
eukaryote, three mouse genes have been cloned, characterized, and
identified as RA synthases, designated Has-1, Has-2, and Has-3.
Expression of mouse Has-2 and Has-3 leads to hyaluronan biosynthesis
in transfected mammalian cells. Has-2 and Has-3 expressing cells
in culture form significant pericellular coats consisting of hyaluronan,
implying these are the vertebrate HAS enzymes. The human genes have
also been cloned and characterized. The HAS-2 gene appears to be
the major player in HA synthesis. A HAS-2 promoter-reporter stable
cell line will be constructed, and formatted as an assay ready for
high throughput screening (HTS). Lead compounds discovered utilizing
this assay, have potential as drugs for arthritis, and/or as topical
anti-wrinkle agents, or for other disease indications.
A unique electrospinning technique to produce bioabsorbable polymer
membranes (polylactide (PLA), polyglycolide (PGA) and copolymers)
has been developed in Chu/Hsiao laboratory in Department of Chemistry
at Stony Brook. The membranes are designed for uses in prevention
of post-operative adhesions, which overcome several problems in
commercial products. The goal of this proposal is to request the
funding for a Phase I Seed Grant to initiate an in-vivo study of
the membrane (by Brathwaite) in the Department of Surgery at the
University Hospital and Medical Center in order to commercialize
these novel materials. The detailed animal testing protocol and
animal use plans are outlined in this proposal. If successful, many
aspects of this technology (material compositions, fabrication techriiques,
procedures and applications) can be patented. A preliminary economic
evaluation indicates that the potential financial return based on
this technology is quite substantial and will be of major benefit
to New York State. |
