Paradigm Biopharmaceuticals (ASX: PAR) claims it has made a “ground-breaking discovery” as part of its ongoing development of pentosan polysulfate sodium (PPS), an antithrombotic agent that reduces joint pain.
The biotech company conducted research into PPS to prove that bone cells under the cartilage produce the pain mediator known as “NGF” and looked into whether PPS is able to reduce the production of NGF by those bone cells.
After undergoing peer-review, the research has now been published in the scientific journal, PLoS One, titled “Human osteocyte expression of Nerve Growth Factor: the effect of PPS and implications for pain associated with knee osteoarthritis”.
According to the authors of the study, PPS (also known as Zilosul) is a promising therapeutic agent for blocking knee pain in individuals with knee osteoarthritis (KOA), although its mode of action in this context remains “unknown”.
According to Paradigm, bone cells produce high levels of the pain mediator NGF, and even more interestingly, that PPS can reduce the production of NGF by implementing a “novel mechanism”.
The company said it can use PPS to reduce the production of NGF not by blocking the NGF, but rather, by operating at the mRNA level to reduce the production of NGF by the bone cells thereby reducing the joint pain.
When PPS is added to TNF stimulated bone cells it showed a statistically significant reduction in the secretion of NGF, being the potential source of pain within patients with OA.
Paradigm said its data provides evidence that PPS may act at multiple levels to suppress the release of NGF, and potentially, other pain mediators in the subchondral bone, to ameliorate pain associated with knee osteoarthritis (OA).
OA is a complex, heterogeneous disease involving the whole joint which includes different types of cells within different tissues such as cartilage, bone, synovial layer, menisci and ligaments.
The ability of PPS to have multiple actions implies it could be an effective agent that manages both clinical symptoms and disease progression that “to our knowledge has not been demonstrated in clinical trials of other drugs under development to treat osteoarthritis,” the company said.
The discovery of a new set of features could allow PPS to be used in additional ways could potentially make Paradigm’s lead drug candidate more commercially valuable.
“We are impressed that our study was the first to identify osteocytes as the key cells within the subchondral bone that are responsible for the production of the insidious pain in knee OA patients. Most importantly, the scientific validation that PPS inhibits NGF as a mediator of bone pain in OA is a ground-breaking discovery for Paradigm,” said Paul Rennie, chief executive officer of Paradigm Biopharmaceuticals.
Mr Rennie also said that he believes Paradigm’s research should alert the interest of ‘big pharma’ who are actively trying to deal with an opiate crisis by developing pharmaceutical agents that are non-opioid, nonaddictive, safe and efficacious.
The use of chemical drugs, or opiates, has reportedly led to a spike in overdoses and suicides, both linked to the use of opioid drugs. The death rate from drug overdoses more than tripled between 1999 and 2017 in the US, while opioid overdoses increased six-fold during the same period.
As a result of the existing opiate crisis, pharmaceutical companies that lead most drug development have spent billions of dollars developing non-opioid agents specifically targeting NGF. Therefore, Paradigm’s new discovery could end up becoming a “very attractive commercial partnership opportunity”, the company said.
“We are showing that PPS as the active agent within our product Zilosul, a pharmaceutical agent that curbs the disease process involved in OA at every level – more specifically, inflammation, cartilage protection and pain,” said Mr Rennie.
“We continue on the pathway to commercialise Zilosul and believe this ground-breaking discovery will further attract commercial interest in Paradigm’s clinical development,” he added.