An Overview of a Novel, Water-Soluble Undenatured Type II Collagen (NEXT-II)

Abstract

Background: Osteoarthritis, the most common form of arthritis, is a crippling, chronic debilitating bone disease that commonly affects humans, dogs, and horses. Inflammation and inflammatory responses are key factors for causing swelling, redness, pain, and loss of movement in arthritic animals and humans.

Methods and Results: We developed a novel, water-soluble, undenatured type II collagen (NEXT-II) for osteoarthritis. NEXT-II demonstrated broad-spectrum safety and nonmutagenicity. NEXT-II exhibited significant efficacy in ameliorating pain and inflammation in collagen-induced arthritis in mice. NEXT-II enhanced the proportion of CD4+CD25+T cells, and gene expressions of stimulated dendritic cells induced markers for regulatory T cell such as forkhead box p3, transforming growth factor-β1, and CD25. Furthermore, NEXT-II was assessed in moderately arthritic dogs receiving either placebo or 10 mg NEXT-II over a period of 150 days. NEXT-II exhibited a significant reduction in overall pain, pain after limb manipulation, and pain after physical exertion compared to the control dogs. Physical health and serum chemistry (alanine aminotransferase, blood urea nitrogen, and creatine kinase) were not altered when these arthritic dogs were treated over a period of 150 days.

Conclusions: These results demonstrate the broad-spectrum safety and efficacy of NEXT-II in ameliorating the symptoms of arthritis.

Key Teaching Points:

•A novel, water-soluble, undenatured type II collagen (NEXT-II) was developed for osteoarthritis.

•The safety studies including acute oral and dermal toxicity, primary dermal and primary eye irritation, Ames’ bacterial reverse mutation assay, mouse lymphoma assay, and 150-day long-term safety studies were conducted.

•NEXT-II exhibited significant efficacy in ameliorating pain and inflammation in collagen-induced arthritis in mice.

•NEXT-II exhibited a significant reduction in overall pain in moderately arthritic dogs without changing physical parameters.

Key words:

• Type II collagen
• osteoarthritis
• safety

ACKNOWLEDGMENTS

The safety studies were conducted in Eurofins/Product Safety Laboratories (Dayton, NJ), INTOX Pvt Ltd. (Pune, India), and Bioservice Scientific Laboratories (Planegg, Germany). Molecular and mechanistic studies were conducted in Showa Pharmaceutical University (Tokyo, Japan). Dog studies were conducted in the Veterinary Division of Murray State University (Murray, Kentucky).

Funding

These studies were supported by a research grant from Ryusendo Co. Ltd., Japan.