Joint replacement surgery for arthritis may not be needed in the future
A new molecule may allow patients to opt for a shot instead of joint replacement surgery in the future
https://news.usc.edu/136787/joint-replacement-surgery-for-arthritis-may-not-be-needed-in-the-future/
BY Cristy Lytal
MARCH 6, 2018
The ability to regenerate joint cartilage cells instead of surgically replacing joints would be a big boon for future patients; image shows microscopic view of joint cartilage cells. (Photo/Nancy Liu, Denis Evseenko Lab, USC Stem Cell)
Will there be a time when joint replacement surgery for arthritis could be avoided in favor of a shot? USC Stem Cell scientist Denis Evseenko has reason to be optimistic.
In a new publication in the Annals of Rheumatic Diseases, Evseenko’s team describes the promise of a new molecule named Regulator of Cartilage Growth and Differentiation, or RCGD 423 for short.
Discovered by the Evseenko team, the molecule enhances regeneration while curbing inflammation. When the scientists applied it to joint cartilage cells in the laboratory, these cells proliferated more and died less. When the scientists injected it into the knees of rats with damaged cartilage, the animals could more effectively heal their injuries.
RCGD 423 exerts its effects by communicating with a specific molecule in the body. This molecule, called the gp130 receptor, receives two very different types of signals: those that promote cartilage development in the embryo and those that trigger chronic inflammation in the adult. It amplifies the gp130 receptor’s ability to receive the developmental signals that can stimulate cartilage regeneration, while blocking the inflammatory signals that can lead to cartilage degeneration over the long term.
Given these auspicious early results, the team is already laying the groundwork for a clinical trial to test RCGD 423 or a similar molecule as a treatment for osteoarthritis or juvenile arthritis.
The goal is to make an injectable therapy for an early to moderate level of arthritis.
Denis Evseenko
“The goal is to make an injectable therapy for an early to moderate level of arthritis,” said Evseenko, associate professor of orthopedic surgery and stem cell biology and regenerative medicine at the Keck School of Medicine of USC. “It’s not going to cure arthritis, but it will delay the progression of arthritis to the damaging stages when patients need joint replacements, which account for a million surgeries a year in the U.S.”Denis Evseenko
Evseenko sees RCGD 423 as a prototype for a new class of anti-inflammatory drugs with a broad range of indications. The lab has already developed several structural analogs of the molecule with varying biological effects and potency. His lab is partnering with scientists at USC and beyond to explore the broader potential of these molecules to treat rheumatoid arthritis, jaw arthritis, lupus, neurological and heart diseases and baldness, as well as to maintain pluripotent stem cells in the laboratory.
Gene Therapy for Rheumatoid Arthritis gets Approval to Start Clinical Trials
FROM THE CLINIC
Clara Rodríguez Fernández on 17/02/2017
https://labiotech.eu/arthrogen-gene-therapy-rheumatoid-arthritis/
Arthrogen will start a Phase Ib trial for a gene therapy aiming to treat rheumatoid arthritis with a single injection and reduce costs for patients.
Arthrogen, based in Amsterdam, is developing local gene therapies for inflammatory diseases. The biotech company has now announced it has received approval to start a Phase Ib trial with its lead candidate, ART-I02, in patients with rheumatoid arthritis who still suffer from inflamed joints despite multiple treatments.
The clinical trial will be conducted by the Centre for Human Drug Research (CHDR) in Leiden, with collaboration from other University Medical Centers in the Netherlands. Patients will start to be recruited in the first quarter of this year and results are expected by the end of 2018.
ART-I02 consists of a recombinant adeno-associated viral vector (rAAV) genetically engineered to encode the human interferon β (hIFN-β) protein, which has anti-inflammatory activity. By including an inflammation-inducible promoter in the genetic construct, the gene is only expressed when the patient suffers flares of acute pain and inflammation.
Founded in 2005 as a joint venture between the Dubai Bone & Joint Center (DBAJ) in the United Arab Emirates and the Academic Medical Center (AMC) in Amsterdam, Arthrogen has managed to raise almost €15M so far to support its pipeline for inflammatory disease.
One of the advantages of ART-I02 is that it’s delivered locally in the rheumatic joint, only affecting the target area to minimize side effects. In addition, gene therapy offers a long-lasting treatment with a single injection, which can significantly reduce costs for patients in the long term. However, Arthrogen will have to be careful to not follow the steps of its neighbor uniQure, whose first commercial gene therapy was a failure because of pricing issues.
Rheumatoid arthritis is a big market, expected to generate €32.5B ($34.6B) by 2020. The space is crowded, but by then blockbusters like top-seller Humira will no longer be protected by patents in both the US and Europe, leading the way for biosimilars and other options affordable in the long term such as gene therapy.