New data suggest that AKL Therapeutics’ investigational oral osteoarthritis (OA) drug APPA may have a dual effect on age-related cellular senescence.
Senescence, a process in which cells stop dividing, plays a major role in the development of many age-related diseases, including 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 reduce the number of harmful senescent cells which build up in the cartilage causing inflammation (a ‘senolytic’ effect), and could also potentially reverse the senescence process so cells can function normally again (a ‘senomorphic’ effect).
The study found that APPA significantly reduced the number of senescent cells and increased the number of cells in the chondrocyte cell line in which senescence had been induced.
Alan Reynolds, Chief Scientific Officer at AKL Therapeutics, said: “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 OA 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.”
A new frontier in medicine
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.
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. Senotherapeutics have the potential to increase healthspan by delaying the worse effects of ageing.
APPA is fixed-dose combination of two synthetically produced, synergistic, secondary metabolites of plant origin. It has been shown to reduce levels of cartilage-damaging enzymes and levels of bone destruction.
AKL is now raising funding for a Phase IIb trial of APPA as a potential treatment for patients with more severe OA – the largest patient group which also has the highest unmet need.
AKL was granted an Innovation Passport for APPA in 2021 by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) which sets out an accelerated roadmap of future development and regulatory milestones.