AFL players are reportedly being treated with injections of the drug pentosan polysulphate sodium (PPS) for knee and bone pain.
While PPS is approved for use in Australia in oral capsule form to treat bladder inflammation, it is not yet approved as an injection for joint problems.
Up to 50 current and former AFL players are reported to have been given PPS over the past few months, under the Therapeutic Goods Administration’s special access scheme.
PPS is not prohibited by the Australian Sports Anti-Doping Authority (ASADA). The drug is neither an anabolic steroid nor an opioid-based pain reliever so is not considered to enhance performance.
Normal use
Pentosan polysulphate sodium was first developed in 1949 by German researcher W. Benend to treat blood clots.
In Australia, PPS is available only by prescription, under the brand name Elmiron, for the treatment of interstitial cystitis, a type of chronic inflammation of the bladder wall. It is not commonly used, with only 400 scripts filled nationwide in 2011.
The drug is a semi-synthetic chemical that works by passing through the kidneys into urine, where it is then able to coat the inner walls of the bladder. This prevents microorganisms attaching to the bladder and causing infections.
When taken in capsule form at a dose of 100 mg, the drug is effective after six to eight weeks of treatment.
PPS is available in Australia with a prescription under the brand name Elmiron. Author provided
Because it is also similar to heparin, PPS also works an anti-blood clotting agent by inhibiting the action of an enzyme called activated factor Xa, which plays a key role in helping blood cells stick together in clotting.
Common side effects of PPS include swelling, headache, dizziness, nausea, indigestion or diarrhoea.
Other uses
The Australian pharmaceutical company Paradigm Biopharma is looking to repurpose PPS as a treatment for pain in people with osteoarthritis of the knee and lesions in the subchondral bone – the layer of bone just below the cartilage in joints which acts as a so-called “shock-absorber”.
The company is currently conducting a randomised, placebo-controlled clinical trial in Australia using an injectable form of the drug. Evidence of the benefit of PPS in osteoarthritis of the knee has been known from an early trial which gave the drug as an intramuscular injection for a month.
It’s not clear how PPS reduces joint pain, but Professor Jegan Krishnan, an orthopaedic surgeon at Flinders University, suggests that the drug has anti-inflammatory effects and seems to address the bone marrow lesions. By controlling the lesions, the drug prevents the pain.
The injectable form of PPS is not registered in Australia, or approved for sale. It can only be used through the TGA’s special access scheme, which grants permission for use of unapproved drugs when other treatment options have been exhausted.
Paradigm Biopharma is not the only company looking to repurpose the drug. Clinical trials are also being conducted overseas by other companies to examine whether PPS is useful as a treatment for psychotic disorders and prostate inflammation.
AFL player treatment
Arthritis and joint pain are common injuries among elite sports people. These injuries are particularly prevalent in Aussie rules players because of the frequent jumping, running and tackling that the players undergo on a weekly basis.
As such, AFL players are one group of sportspeople who are likely to benefit from PPS injections.
PPS is administered as an injection to the players twice a week for a period of six weeks and results have indicated that PPS works well to control their knee pain. All players reportedly experienced significant drops in their pain levels.
While these results are promising, any data obtained outside of the clinical trial must be treated with caution. Before routine prescribing of PPS for people with knee pain and bone lesions, the clinical trial must show the drug is safe in its injectable form and that any reduction is pain is at least as good as current treatments.
Author: Nial Wheate - PhD FRACI CChem FHEA - University of Sydney
Associate Professor Wheate completed a Bachelor of Science degree with 1st class honours from the University of New South Wales whilst at the Australian Defence Force Academy. He then completed a PhD in medicinal chemistry under Professor J. Grant Collins. Since then he has worked in the School of Biomedical and Health Sciences at the University of Western Sydney (Australia) and the Strathclyde Institute of Pharmacy and Biomedical Science (Scotland) before taking up a position in the Faculty of Pharmacy at the University of Sydney (Australia) in 2012. Associate Professor Wheate is currently the Program Director of the pharmacy undergraduate degrees at The University of Sydney and was previously the Head of Cancer Research in the Faculty of Pharmacy. He holds the positions: Member, Academic Board of The University of Sydney Member, University Executive - Student Life Committee Member, Undergraduate Studies Committee (As nominee of the Academic Board) Associate Professor Wheate's research interests lie in drug delivery and pharmaceutical formulation. He has a particular research interest in the drug delivery application of macrocycles (including cyclodextrins, cucurbiturils, calixarenes, and pillararenes) and their host-guest complexes.
