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Hyalgan

Hyaluronan (also called hyaluronic acid or hyaluronate) is a glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues. It is one of the chief components of the extracellular matrix, contributes significantly to cell proliferation and migration, and may also be involved in the progression of some malignant tumors. more...

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Functions

Until the late 1970s, hyaluronan was described as a "goo" molecule, a ubiquitous carbohydrate polymer that comprised the extracellular matrix. For example, hyaluronan is a major component of the extracellular matrix that constitutes synovial fluid. Along with lubricin, it is one of the fluid's main lubricating components. It helps protect joints by increasing the viscosity of the fluid and by making the cartilage between bones more elastic.

While it is found in large numbers in extracellular matrices, hyaluronan also contributes to tissue hydrodynamics, movement and proliferation of cells, and participates in a number of cell surface receptor interactions, notably those including its primary receptor in vivo, CD44. Upregulation of CD44 itself is widely accepted as a marker of cell activation in lymphocytes.

Hyaluronan's contribution to tumor growth may be due to its interaction with CD44. CD44, the chief in vivo hyaluronan receptor, participates in cell adhesion interactions required by tumor cells. Some of the enzymes that break down hyaluronan are known tumor suppressants; paradoxically, the gene for hyaluronidase-2 is an oncogene and promotes tumor growth.

Structure

The chemical structure of hyaluronan was determined in the 1950s in the laboratory of Karl Meyer. Hyaluronan is a polymer of disaccharides themselves composed of D-glucuronic acid and D-N-acetylglucosamine, linked together via alternating beta-1,4 and beta-1,3 glycosidic bonds. Polymers of hyaluronan can range in size from 10² to 10⁴ kDa in vivo.

Hyaluronan is energetically stable in part because of the stereochemistry of its component disaccharides. Bulky groups on each sugar molecule are in sterically favored positions while the smaller hydrogens assume the less favorable axial positions.

Synthesis

Hyaluronan is synthesized by a class of integral membrane proteins called hyaluronan synthases, of which vertebrates have three types: HAS1, HAS2, and HAS3. These enzymes lengthen hyaluronan by repeatedly adding glucuronic acid and N-acetylglucosamine to the nascent polysaccharide.

Degradation

Hyaluronan is degraded by a family of enzymes called hyaluronidases. In humans, there are at least seven types of hyaluronidase-like enzymes, several of which are tumor suppressors. The degradation products of hyaluronan, the oligosaccharides and very low molecular weight hyaluronan, exhibit pro-angiogenic properties.

Medical applications

Hyaluronan is naturally found in many tissues of the body such as skin, cartilage, and the vitreous humor. It is therefore well suited to biomedical applications targeting these tissues. The first hyaluronan biomedical product, Healon, was developed in the 1970s and 1980s and is approved for use in ophthalmic surgery (i.e. corneal transplantation, cataract surgery, glaucoma surgery and retinal attachment surgery). Other biomedical companies also produce brands of hyaluronan for ophthalmic surgery .

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Orthologic Announces Termination of Hyalgan Co-Promotion Agreement With Sanofi-Synthelabo
From Business Wire, 10/9/00

Business Editors/Health & Medical Writers

TEMPE, Ariz.--(BW HealthWire)--Oct. 9, 2000

Decision is Part of OrthoLogic's Strategic Plan to Focus Increased

Attention on its Proprietary Orthopedic Products

OrthoLogic Corp. (Nasdaq:OLGC) today announced that the company and Sanofi-Synthelabo, Inc. have mutually agreed to terminate their Hyalgan(r) co-promotion agreement.

In exchange for the return of OrthoLogic's rights to Sanofi to sell Hyalgan to the orthopedic market, OrthoLogic received an upfront cash payment, financial incentives to complete a successful transition of the business, and continuing royalties for the next two years on all U.S. sales of Hyalgan in all market segments.

Hyalgan (sodium hyaluronate), a product administered by injection directly into the knee joint for relief of pain in mild to moderate osteoarthritis of the knee, was developed by Fidia SpA of Italy and is marketed in the U.S. by Sanofi-Synthelabo and OrthoLogic.

In June 1997, OrthoLogic signed a co-promotion agreement with Sanofi-Synthelabo for the rights to sell Hyalgan in the U.S. orthopedic market. The initial term of the agreement was for five years, with provisions for extensions at the discretion of Sanofi. Recent changes in strategic direction for both companies regarding the orthopedic market led to a mutual decision to terminate the agreement at the end of 2000.

The companies have agreed to use the fourth quarter of 2000, beginning immediately, as a transition quarter, with Sanofi assuming all sales and marketing responsibility for all markets beginning in January 2001.

"We are very pleased to have reached a mutually acceptable agreement with Sanofi regarding Hyalgan," said Thomas R. Trotter, president and CEO of OrthoLogic. We plan to work very closely with Sanofi during the remainder of this year to effectuate a smooth transition of the business."

Trotter added, "Achieving this agreement with Sanofi was a key element of our long-term plan to shift more attention back to our own proprietary product lines to further enhance their positions in the orthopedic marketplace.

"The financial terms of this agreement will provide OrthoLogic with a considerable increase in our investment capacity as well as provide us with continuing royalty income for 2001 and 2002. The agreement is expected to result in a one-time financial gain in the fourth quarter ending December 31, 2000, for OrthoLogic"

OrthoLogic develops, manufactures and markets proprietary, technologically advanced orthopedic devices designed to promote the healing of musculoskeletal tissue. Founded in 1987, the company is located in Tempe, Ariz. For more information, please visit the company's Web site: www.orthologic.com.

Statements in this release that are not historical may be deemed forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Although the company believes the expectations reflected in any forward-looking statements are based on reasonable assumptions, it can give no assurance that its expectations will be attained. These forward-looking statements involve risks and uncertainties that could cause actual results to differ materially.

For a more complete description of the risks and uncertainties that face the company, please see the company's annual report on Form 10-K for the fiscal year ended December 31, 1999, the company's quarterly report on form 10-Q for the period ended June 30, 2000, and other documents filed by the company with the Securities and Exchange Commission.

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