Promedior Announces Publication of New Research Demonstrating Pentraxin-2/SAP is a Potent Inhibitor of Asthma and Asthma-Induced Lung Fibrosis

Novel Therapeutic Approach Directly Regulates A Fundamental Immune Mechanism, Macrophage Differentiation

 

MALVERN, Pa.--(BUSINESS WIRE)--Sep 7, 2010 - Promedior, Inc., a clinical stage biotechnology company developing novel therapies to treat fibrotic and inflammatory diseases, announced today the publication of collaborative research in the Journal of Allergy and Clinical Immunology entitled, “Serum amyloid P attenuates M2 macrophage activation and protects against fungal spore–induced allergic airway disease.” The research showed that human Pentraxin-2 protein (PTX-2, also called human SAP), a pentraxin therapeutic compound, potently inhibits M2 macrophage differentiation and represents a novel therapeutic approach for the treatment of asthma. This builds on the body of research showing PTX-2/SAP's unique role in regulating a fundamental mechanism of the innate immune system and activating the body's natural ability to resolve tissue damage in disease processes that cause fibrosis and inflammation.

In this study, researchers examined the effect of various pentraxin proteins in an experimental model of fungal-induced allergic airway disease, a condition associated with increased severity of asthma. Results showed:

 

  • PTX-2/SAP potently inhibited undesirable M2 macrophage differentiation both in vitro and in vivo, blocking their responsiveness to type-2 cytokines which are strongly associated with asthma and fibrotic lung diseases.
  • Fungal sensitized mice, challenged with live fungal spores and subsequently treated with PTX-2/SAP had dramatically less inflammation, mucus production and fibrosis, and had improved lung function.
  • Adoptive transfer of M2 macrophages into fungal sensitized and challenged mice resulted in exacerbated inflammation and fibrosis in the lung, whereas adoptive transfer of naïve macrophages reduced inflammation and fibrosis.
  • Treatment of M2 macrophages with PTX-2/SAP prior to adoptive transfer altered M2 macrophage function thereby restoring the ability of these cells to reduce inflammation and fibrosis and was associated with a significant increase in IL-10 production in the lung.

“Our research shows that PTX-2/SAP has prominent immunomodulatory effects on M2 macrophages, thereby providing a mechanism for its ability to prevent the development of and reverse established fungal airway disease,” said lead author Ana Paula Moreira, Ph.D., University of Michigan Medical School, Ann Arbor. “Further investigation of the therapeutic effect of PTX-2/SAP in clinical asthma progression and exacerbation is a promising area for future research.”

Promedior is developing a pipeline of drugs based upon recombinant forms of PTX-2/SAP for the treatment and prevention of fibrotic and inflammatory diseases, and is conducting human clinical studies to evaluate Pentraxin-2 therapeutics for a number of diseases.

“These new findings significantly contribute to the large body of data supporting that Pentraxin-2 has a fundamental opportunity to treat many kinds of inflammation and fibrosis, and we believe it will have broad application across many severe and chronic inflammatory and fibrotic diseases,” said Mark L. Lupher, Jr., Ph.D., Chief Scientific Officer, Promedior. “We believe this opens the door for a new and powerful way to regulate M2 macrophages and fibrocytes using Pentraxin-2-based therapeutics and a new path for discovering novel treatments for patients.”

Asthma is a chronic pulmonary disorder that predisposes patients to reversible episodes of airway obstruction resulting in resistance to inhalation and in severe cases to lung fibrosis. Fungal spores are ubiquitous environmental inhalants that aggravate or exacerbate asthmatic responses in asthma patients. Fungal-sensitivity in asthmatic patients is often associated with increased severity of disease and a type-2 cytokine profile in the lung. These type-2 cytokines can stimulate the appearance of M2 or “alternatively activated” macrophages which are strongly associated with fibrotic lung disease, and may contribute to the severity of asthma.

About Pentraxin Therapeutics

Promedior's proprietary platform of pentraxin therapeutics is based upon breakthrough discoveries in how the body's innate response to injury results in pathologic fibrosis and the loss of tissue and organ function. Promedior's novel therapeutics are designed to treat and prevent fibrotic pathology by regulating the common cellular mechanisms that control the initiation and progression of fibrosis across a variety of tissues and organ systems. Promedior's initial drug products are based upon the unique structure of Pentraxin-2, a naturally-occurring protein which has demonstrated a unique role in targeting monocytes at sites of tissue damage. Promedior's approach leverages the natural role of Pentraxin-2 in regulating the response of important immune and inflammatory processes in the body. Promedior has built a comprehensive patent estate for Pentraxin therapeutics, including recombinant human Pentraxin-2 (rhPTX2 or rhSAP), for a broad range of therapeutic applications in fibrosis and other inflammatory diseases.

About Promedior

Promedior has developed a novel drug discovery platform to regulate the monocyte-derived cell populations that play key roles in fibrotic, inflammatory and autoimmune diseases. By specifically targeting these cells at the site of injury, Promedior is able to treat the source of aberrant immune system responses, promote tissue healing and resolution, and greatly reduce the risk of systemic side effects inherent in current therapeutic approaches. Utilizing this novel approach, Promedior is initially developing drugs to address the most severe and difficult-to-treat fibrotic and inflammatory conditions of the eye, lung and kidney such as glaucoma, age-related macular degeneration, diabetic retinopathy and dry eye disease (eye); pulmonary fibrosis, scleroderma and COPD (lung); and acute and chronic nephropathy (kidney). For additional information about Promedior, please visit http://www.promedior.com.

 

Contact: The Yates Network
Kathryn Morris, 845-635-9828
kathryn@theyatesnetwork.com

 

 

Posted: September 2010

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