Osteoarthritis / New Breakthrough Osteoarthritis Molecule

New Breakthrough Osteoarthritis Molecule
10
Aug

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  • arthritis treatment . Denis Evseenko . OA . osteoarthritis . osteoarthritis molecule . USC .

Osteoarthritis (OA) is a chronic degenerative joint disease that affects 27 million Americans and ultimately leads to irreversible joint damage. Over time, OA destroys the smooth layer of articular cartilage that cushions the ends of bones where they come together to form joints. As the disease progresses, the cartilage thins, fluid leaks into the joint lining, and bones begin to grind together, causing pain, swelling, and loss of motion.

Denis Evseenko, MD, PhD, Associate Professor of Orthopaedic Surgery, Stem Cell Research and Regenerative Medicine at the Keck School of Medicine of the University of Southern California (USC), is accelerating the discovery of novel ways to heal damaged joints and regenerate healthy tissue.

“Currently, the only treatments for osteoarthritis are pain control and total joint replacement,” says Dr. Evseenko. “New strategies to prevent OA and repair damaged cartilage are urgently needed.”

In the hope of translating basic research into vital therapies, Dr. Evseenko’s lab is investigating two complementary approaches.

“We are in the late stages of preclinical development of a potential molecule (drug) that appears to have profound anti-inflammatory and growth-stimulating activity,” he explains. “At the same time, we are working to scale up the production of stem cells that can become cartilage, which can be implanted into joints to repair localized defects.”

Deni Evseenko | Osteoarthritis Research Breakthrough

In 2015, Dr. Evseenko, then a junior faculty member, began a pilot research program with funding from the Arthritis National Research Foundation. Today, his goal remains the same — to develop drug therapies and regenerative stem cells to repair cartilage damage. His lab at USC is currently funded by private venture capital and government grants, including a recent $2.5 million grant from the California Institute for Regenerative Medicine (CIRM).
 

New Osteoarthritis Molecule Helps Regenerate Joints

Osteoarthritis is driven by the body’s inflammatory response to repetitive stress or injury. Chronic “wear and tear” often contributes to OA and painfully disrupts the delicate workings of the joint, permanently damaging the underlying bone and connective tissues.

Although total joint replacement surgery relieves pain, artificial joints typically last only about 15-20 years, necessitating “revision” surgery later in life.

Some of the youngest people to experience osteoarthritis are professional athletes. Professional athletes with deteriorating joints often develop significant symptoms of arthritis 10 years after an injury occurred. Because younger people have better regenerative powers, athletes are the initial target population for early interventions based on Dr. Evseenko’s pioneering research.

Could this new osteoarthritis molecule stimulate cartilage regrowth by returning cells to an earlier developmental stage? Could stem cell grafts be used to repair damaged cartilage? And, will a combined approach someday replace joint replacement surgery?

In his two-part process Dr. Evseenko first uses a new approach with pluripotent stem cells, stem cells which can generate into any cell type in the body, to generate long-lasting articular cartilage. He anticipates that this new stem cell therapy could reach human clinical trials within three years and he is also exploring ways to successfully bank regenerated cells for future use in cartilage tissue repair.

Dr. Evseenko believes that stem cell-based therapy may eventually lead to transplants for patients with cartilage injury or degenerative arthritis, potentially delaying or even preventing the need for total joint replacement.

In the second part of their approach, Dr. Evseenko and his team are currently beginning large animal trials to test a breakthrough osteoarthritis molecule (drug candidate) that may stimulate the regeneration and growth of new cartilage.

Osteoarthritis Molecule | Cartilage Regeneration
ANRF Board Member, Kevin Donohue, peers into a tube with live cartilage generation ongoing while touring the Evseenko Lab

Since cartilage has very limited ability to regrow, the discovery of a drug that reverts cells and stimulates the ability for rapid cell division like when in the womb would be a major advance in cartilage regeneration and repair. This molecule can be used to regenerate joints in complement to stem cell therapy or without stem cells altogether, depending on the severity of the osteoarthritis.

However, before any drug goes on the market, it must undergo extensive testing to assure that it’s safe and effective. “It’s difficult to predict when any drug will reach patients,” Dr. Eveseenko explains. “Once a potential drug begins clinical trials, the process becomes more about the regulatory agencies and less about the science.”
 

The Valley of Death

Beyond sheer energy and talent, scientists are engaged in an endless struggle to secure the research dollars that support their discoveries. Early in his career, Dr. Evseenko experienced the limitations of therapeutic opportunities for scientists doing basic research. He saw many hopeful discoveries die before they ever reached patients who are eagerly awaiting a cure. Today, he urges funders to continue fueling the breakthroughs so vital to the discovery of new therapies and reiterates how important funding, from foundation’s like the Arthritis National Research Foundation, is to pushing the research field forward.

Researchers in the biomedical field have a specific term for the crucial moment when funding for basic research runs out, they call it the “valley of death.” There are few who want to take a chance on a multimillion-dollar experimental therapy that may fail.

“Say you come up with a promising small molecule, but you don’t know if it will be safe and efficient in a large animal study,” he says. “It’s no longer research — now it’s drug development, which costs millions. You talk to Big Pharma and biotech venture capital, but what if it’s toxic or unsafe? As a result, 95% of researchers drop the idea, get a grant to study something else, and never go on to the next stage.”

Dr. Evseenko is among the lucky few who has received grants to continue work that began with his early research grant from ANRF. “Thanks to those first steps with stem cells, my lab is translating arthritis research into potential new therapies bringing hope of relief to the millions of people worldwide suffering from osteoarthritis.”

But there is more work to be done for Dr. Evseenko and all of the Arthritis National Research Foundation researchers. The Foundation cannot support this research without the help of the Cure Arthritis community, through awareness, fundraising and donations. Researchers like Dr. Evseenko depend on the community coming together so they can further their work and push for better treatments and cures.



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