A groundbreaking study from the University of Adelaide reveals that osteoarthritis may be reversible through a new treatment targeting Gremlin 1 gene-marked stem cells. With promising results from stimulating these cells in mice, and human trials in progress following a successful five-year study, this research challenges the traditional view of osteoarthritis and suggests a potential paradigm shift in its treatment.
Existing therapies for osteoarthritis focus on symptom relief instead of tackling the root cause of the disease. However, recent research conducted by the University of Adelaide has shown the condition may be treatable and reversible.
Osteoarthritis involves the breakdown of cartilage and surrounding joint tissues and is the most common form of arthritis in Australia, with 20% of individuals over 45 years old suffering from it.
It is a long-term and progressive condition that affects people’s mobility and has historically had no cure. Its treatment cost the Australian health system an estimated $3.9 billion in 2019-20.
Groundbreaking Research on Stem Cells
Often described as a ‘wear and tear’ condition, factors such as aging, obesity, injury, and family history contribute to the progression of osteoarthritis.
University of Adelaide researchers discovered a novel population of stem cells – marked by the Gremlin 1 gene – responsible for the progression of osteoarthritis.
Treatment with fibroblast growth factor 18 (FGF18) stimulated the proliferation of Gremlin 1 cells in joint cartilage in mice, leading to significant recovery of cartilage thickness and reduced osteoarthritis.
Gremlin 1 cells present opportunities for cartilage regeneration and their discovery will have relevance to other forms of cartilage injury and disease, which are notoriously challenging to repair and treat.
It challenges the categorization of osteoarthritis as wear and tear.
A Paradigm Shift in Osteoarthritis Treatment
“The findings of our study reimagine osteoarthritis not as a ‘wear and tear’ condition but as an active, and pharmaceutically reversible loss of critical articular cartilage stem cells,” said the University of Adelaide’s Dr Jia Ng from the Adelaide Medical School, who co-led the study.
“With this new information, we are now able to explore pharmaceutical options to directly target the stem cell population that is responsible for the development of articular cartilage and progression of osteoarthritis.”
While Dr Ng describes current treatments for osteoarthritis as a “Band-Aid approach”, this new understanding could lead to a pharmaceutical treatment that reverses osteoarthritis and helps to address health outcomes associated with the disease.
“Known comorbidities of osteoarthritis include heart, pulmonary, and kidney disease, mental and behavioral conditions, diabetes, and cancer,” said Dr. Ng.
“Our study suggests that there may be new ways to treat the disease rather than just the symptoms, leading to better health outcomes and quality of life for people who suffer from osteoarthritis.”
Towards Human Trials and Treatment Accessibility
Though this discovery is limited to animal models, Dr Ng said there are genetic similarities to human samples, and human trials are ongoing.
“We look forward to the outcome of these trials and to contribute to the better understanding of a pharmaceutical mechanism to treat osteoarthritis,” she said.
Results of a five-year clinical trial study using FGF18, known clinically as Sprifermin, were published in 2021 with potential long-term clinical benefit and no safety concerns.
Phase 3 of the Sprifermin trial is ongoing, and researchers envision public access to this treatment soon.
Reference: “Loss of Grem1-lineage chondrogenic progenitor cells causes osteoarthritis” by Jia Q. Ng, Toghrul H. Jafarov, Christopher B. Little, Tongtong Wang, Abdullah M. Ali, Yan Ma, Georgette A. Radford, Laura Vrbanac, Mari Ichinose, Samuel Whittle, David J. Hunter, Tamsin R. M. Lannagan, Nobumi Suzuki, Jarrad M. Goyne, Hiroki Kobayashi, Timothy C. Wang, David R. Haynes, Danijela Menicanin, Stan Gronthos, Daniel L. Worthley, Susan L. Woods and Siddhartha Mukherjee, 31 October 2023, Nature Communications<em>Nature Communications</em> is a peer-reviewed, open-access, multidisciplinary, scientific journal published by Nature Portfolio. It covers the natural sciences, including physics, biology, chemistry, medicine, and earth sciences. It began publishing in 2010 and has editorial offices in London, Berlin, New York City, and Shanghai. ” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>Nature Communications.
DOI: 10.1038/s41467-023-42199-1
Source: SciTechDaily
