Treatment of Acne and Inflammatory Conditions by Modulation of Hyaluronan and Hyaluronidase Activity

Tech ID: liu000610

 

Introduction

HA is a linear non-immune glycosaminoglycan polymer of greater than 5,000 Da found in the extracellular matrix throughout connective, epithelial, and neural tissues. Hyaluronan (hyaluronic acid or “HA”) plays an important role in inflammatory disorders. The length of the hyaluronan degradation product determines the specific role played by the molecule in inflammation, either activation or inhibition.

Researchers at Cedars-Sinai Medical Center have identified physiologically relevant size ranges of HA and several bacterial hyaluronidases that produce the fragments. This discovery can support a novel therapeutic approach to treat a broad range of inflammations without development of resistance and side effects caused by current therapies.

 

Technology Description 

The researchers identified physiologically relevant size ranges of HA and bacterial hyaluronidases that produce the fragments. The researchers have elucidatedthe mechanisms of immunosuppression: Hyaluronidases from certain bacteria destroy the pro-inflammatory HA fragments that are abundantly produced in many inflammatory diseases, degrading them to disaccharides. Hyaluronan disaccharides can further inhibit inflammation by blocking the major pro-inflammatory TLR2 and TLR4 pathways.

 

This discovery can be used as a therapeutic approach to treat inflammation without the development of resistance and side effects that are seen in current therapies. The therapeutic compositions include certain hyaluronidases capable of generating HA disaccharides when combined with hyaluronan, and/or the hyaluronan disaccharides themselves, and/or inflammatory hyaluronidase inhibitors.

 

Relevant bacterial hyaluronidases and HA fragments have been tested on mice to treat inflammation. HA disaccharide is shown to decrease acute lung injury.

 

Advantages/Novelty 

• Humans produce abundant pro-inflammatory HA fragments in a number of pro-inflammatory diseases. In some of these diseases, HA fragments are the major cause of inflammation. Currently there are no therapeutics that directly neutralize these fragments.  Bacterial hyaluronidases would represent a unique therapeutic that directly destroys these fragments, thereby targeting the root cause of inflammation for many of these diseases.

• Currently, acne vulgaris is a skin disease that affects most teenagers. Although the fundamental cause of the disease is unknown, it is clear that P. acnes induced inflammation plays a key role and is a major inducer of inflammation.  Inhibition of this enzyme could be an effective and unique strategy for the treatment of acne.

• As a small molecule, HA disaccharide is unlikely to generate resistance by host antibody production.  Since humans can make this product, albeit at a lower level, the disaccharide is likely to have fewer side effects compared to currently available agents.

 

Applications 

HA disaccharide and certain bacterial hyaluronidases can be used to treat a broad range of inflammatory and fibrotic diseases and select cancers. 

 

Intellectual Property 

PCT/US2014/032893 nationalized into US, Canada, China, Europe, India, and S. Korea.

US patent 9,763,969 granted.

 

Patent Information:
For Information, Contact:
Wenyue Du
Senior Associate - IP Management & Licensing
310-423-2241
wenyue.du@cshs.org
Inventors:
George Liu
Pierre Kyme
Keywords:
Inflammatory Disorders