Investigational Oral Osteoarthritis Drug APPA May Have a Promising Senotherapeutic Effect with Potential in Other Diseases of Ageing

New data presented at the 2023 Osteoarthritis Research Society International (OARSI) World Congress in Denver, Colorado suggest that AKL Therapeutics‘ investigational oral osteoarthritis (OA) drug APPA may have a dual effect on senescence1 – a process in which cells stop dividing as a natural consequence of ageing. Senescence plays a major role in the development of many age-related diseases, including osteoarthritis (OA).

The study, using a human chondrocyte (cartilage-forming) cell line, was carried out at the Institute of Biomedical Research of A Coruña (INIBIC) in Spain. It found that APPA appears to not only reduce the number of harmful senescent cells which build up in the cartilage causing inflammation, but could also potentially reverse the senescence process so cells can function normally again. The study found that APPA significantly reduced the number of senescent cells (p=0.020) and increased the number of cells – indicated by the number of nuclei (p=0.062) – in the chondrocyte cell line in which senescence had been induced.

Alan Reynolds, Chief Scientific Officer at AKL Therapeutics, says: “These latest findings raise the tantalising possibility that APPA could modify the progression of debilitating OA for patients by eliminating or delaying the adverse effects of cellular senescence and the process of ageing. Frailty and mobility issues have a significant impact as we age, often leading to people living many years in pain and ill health. If we can reduce senescence, which contributes to joint damage in OA7 and is involved in many other age-related diseases, we can hopefully help improve peoples’ healthspan, so they age in better physical and mental health.”

As we age, dysfunctional senescent cells – often dubbed “zombie” cells – build up in the body while secreting harmful chemicals which cause inflammation and damage surrounding tissue – a process known as senescence. They have become one of the most promising targets for healthy ageing research as senescence is now known to play a major role in the development of many age-related diseases, including OA, Chronic Obstructive Pulmonary Disease (COPD), Alzheimer’s Disease, Parkinson’s Disease, osteoporosis, and diabetes.

Developing a new class of drugs called senotherapeutics to eliminate or delay the damaging effects of this cellular senescence is a new frontier in medicine.10 Senotherapeutics have the potential to increase healthspan by delaying the worse effects of ageing, which would reduce the burden of age-related diseases and could save healthcare systems billions every year.

David Miles, Chief Executive Officer at AKL Therapeutics, says: “With a unique mechanism of action,12-15 APPA is the only oral drug that targets the multiple signalling pathways in bone, cartilage and inflammation involved in OA, delivering pain relief to multiple joints. With this latest data now showing that APPA has a potential senomorphic effect, we’ve recently filed a patent application and will look to carry out further studies on other senescence-related diseases to investigate its potential as a senotherapeutic.”