Osteoarthritis is characterized by the gradual deterioration of cartilage in the joints of the body. The disease affects over 80 percent of the global population aged 60 and older. Cartilage serves as a cushion and shock absorber between bones and facilitates the movement of joints. Breakdown of cartilage leads to pain and impaired mobility. Once gone, cartilage is not replaced.
Cartilage is strengthened by a dynamic lattice-type framework of collagen, proteins,
carbohydrates and fluid known as an extracellular matrix. Marina D'Angelo, PhD, professor, course director for several blocks of the 黑料传送门 One DO curriculum, and founder and chief science officer of ProteaPex Therapeutics, LLC, describes
cartilage's extracellular matrix as a 鈥渟caffolding on which the cells live.鈥�
Dr. D'Angelo, whose research focuses on developing treatments to prevent diseases of bone and joints, explained that when cartilage breaks down over time, the cushioning properties of the extracellular matrix is lost and the cartilage cells gradually are replaced by bone cells leading to the disabling symptoms of osteoarthritis. Joints like the knee, hip and shoulder are commonly affected.
Currently, there are no effective treatments for the reversal of osteoarthritis. Dr. D'Angelo says that some interventions, such as steroid injections or other non-steroidal anti-inflammatory drugs, manage symptoms temporarily but don't address the underlying issue of cartilage destruction. Eventually, patients may require joint replacement surgery to restore mobility and quality of life.
Dr. D'Angelo and her collaborators (Drs. Hafez Selim, Kathryn Behling and Fusun Ozer) have taken a novel approach to preventing the destruction of the extracellular matrix in cartilage and other tissues. Their technology is "a way to interfere with the enzymes that break down the cartilage itself鈥搕he hallmark of osteoarthritis," says Dr. D'Angelo.
The drugs they invented, called extracellular matrix protection factors (ECPFs), are designed to block the ability of degrading enzymes of the matrix metalloproteinase family, to bind and cleave molecules of the extracellular matrix. Extensive testing in cultures of human osteoarthritic cartilage cells obtained from patients undergoing knee replacement surgery and in rodents demonstrated reduction of extracellular matrix degradation and improved mobility.
"What we're using now has the potential to be disease-modifying," says Dr. D'Angelo. These novel, patent-protected drugs are a platform of therapeutics of the 黑料传送门 spin-out company .
The extracellular matrix is also degraded in periodontal disease in which infection leads to softening of the tissue around the teeth. Utilizing gingival fibroblasts isolated from patients with extensive periodontal disease, Dr. D'Angelo's group has demonstrated that ECPF slows the degradation of gum tissue associated with periodontal disease.
Degradation of the extracellular matrix may be accompanied by changes in its composition in the lung resulting in loss of elasticity and reduced gas exchange. Dr. D'Angelo's lab and ProteaPex have been investigating the effects of ECPFs in cultures of lung cells obtained from patients with chronic obstructive pulmonary disease (COPD), with the eventual goal of testing the drugs in animals.
Dogs, like humans, can develop osteoarthritis. The process of disease progression
is similar in the two species. Treatment options for dogs include pharmacological
symptom management or potential knee replacement. These options can temporarily manage
pain, but they may pose serious medical risks to canine companions.
Dr. D鈥橝ngelo says, 鈥淥ur plan to drive the technology forward is to target the companion animal market because of the consistency between what's happening in both dogs and humans. Also, the path to FDA approval for use of our drugs in humans requires testing in animal models of osteoarthritis before beginning clinical trials.鈥�
Osteoarthritis lacks a definitive treatment to reverse disease progression. Currently, drugs are prescribed to reduce pain and inflammation. Osteopathic manipulative therapy aimed at strengthening associated muscles, ligaments, and supporting sheaths of dense extracellular matrix, and promoting blood flow to the joint, may reduce the need for palliative drugs and improve quality of life.
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