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pentosan-polysulfate

PENTOSAN POLYSULFATE

More than 27 million Americans are affected by osteoarthritis, a degenerative disease that is the most common form of arthritis.

Osteoarthritis (OA) is caused by a breakdown of cartilage – the tissue that covers the ends of bones where they form a joint. Healthy cartilage allows bones to glide over one another, and it absorbs energy from the shock of physical movement. In osteoarthritis, the surface layer of cartilage breaks down and wears away. This results in bones under the cartilage rubbing together, causing pain, swelling, and stiffness. Bone spurs can develop, permanently changing the joint’s shape.

OA is by far the most common form of arthritis and has a growing impact on health care. Even now, there is no therapeutic agent that works directly on OA. However, a drug called pentosan polysulfate is showing great promise for the treatment of OA.

Pentosan polysulfate sodium (PPS) Uses

Australian researcher and physician, Dr. Peter Ghosh from the University of Sydney has brought an old drug back into the light for arthritis sufferers. The drug is called pentosan polysulfate sodium (known in medical circles as PPS). To date, trials of the drug involving human patients have been proven highly successful. As PPS eliminates pain associated with arthritic disease by acting on bone marrow lesions that cause pain and cartilage degeneration. By controlling these lesions there is a reduction in symptoms and pain.

PPS is a very safe drug and has been successfully used for 70 years to treat urinary infections in women and is FDA-approved and used for the treatment of interstitial cystitis (or painful bladder syndrome) and deep vein thrombosis. The drug is neither an anabolic steroid nor an opioid-based pain reliever so is not considered to enhance performance.

Benefits of Pentosan

The benefits of pentosan polysulfate for OA sufferers include:

  • Treats bone marrow edema lesions (BMLs)
  • Limiting cartilage deterioration;
  • Promoting new cartilage formation;
  • Thickening the joint fluid – thus acting as a better lubricant;
  • Improving blood supply to the joint, in turn helping it heal;
  • By virtue of these actions, it provides pain relief for a much longer period of time
  • Treats all joints of the body at the same time
  • Inhibits in vitro replication of HIV and other enveloped viruses

Dosage

Suggested dosage: Inject 1ml (250mg) intramuscularly or into intra articular space 1-2 times per week.

Side Effects of Pentosan

Common side effects of PPS include swelling, headache, dizziness, nausea, indigestion, malaise and diarrhea.

how does pentosan work? 

In osteoarthritis, pentosan reduces the destruction of cartilage by affecting inflammatory mediators. It also increases the number of proteoglycans into the extracellular matrix. Proteoglycans are important because they allow tissues like collagen to withstand compression and swelling forces. Joint cartilage also contains Proteoglycans.

In the synovium, the part that surrounds the inner lining of your joint, pentosan increases both the production and the molecular weight of hyaluronan. Hyaluronan or Hyaluronic acid is a compound that occurs naturally in your body, and it is responsible for attracting and retaining moisture. Pentosan also has another anti-inflammatory function due to its fibrinolytic activity. This activity improves the blood flow not only in the synovium but also in the subchondral bone.

Pentosan Polysulfate Studies

Recently, Paradigm Pharmaceuticals an Australian biotech company doing studies on Pentosan had reported an average 51.2% reduction in chronic knee pain by a group of osteoarthritis patients being treated with its injectable Pentosan Polysulfate Sodium drug. Researchers hope that it may work as well in relieving pain in other parts of the body.

Paradigm Biopharmaceuticals also concluded a phase 2A clinical trials of Pentosan Polysulfate to treat viral arthritis caused by mosquito-borne alphavirus infections, including the debilitating Ross River virus (RRV) and chikungunya virus (CHIKV).  The clinical trials passed both safety and efficacy measures amongst participants with chronic RRV-induced arthralgia who were treated with the injectable pentosan polysulfate sodium (PPS). At their three-month follow-up, 72.7% of the study participants treated with PPS showed near remission of symptoms in contrast to those participants who were administered with a placebo (14.3%). 

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Research

Kenji Kumagai, Susumu Shirabe, Noriaki Miyata, Masakazu Murata, Atsushi Yamauchi, Yasuhumi Kataoka and Masami Niwa. Sodium pentosan polysulfate resulted in cartilage improvement in knee osteoarthritis - An open clinical trial. BMC Clin Pharmacol. 2010; 10:7. Published online 2010 Mar 28. doi: 10.1186/1472-6904-10-7. PMCID: PMC2873929. PMID: 20346179

Ghosh P, Edelman J, March L, Smith M. Effects of pentosan polysulfate in osteoarthritis of the knee: A randomized, double-blind, placebo-controlled pilot study. Current Therapeutic Research. 2005;66:552–571. doi: 10.1016/j.curtheres.2005.12.012.

Ghosh P. The pathobiology of osteoarthritis and the rationale for the use of pentosan polysulfate for its treatment. Semin Arthritis Rheum. 1999 Feb;28(4):211-67.

Takizawa M, Yatabe T, Okada A, Chijiwa M, Mochizuki S, Ghosh P, Okada Y. Calcium pentosan polysulphate directly inhibits enzymatic activity of ADAMTS4 (aggrecanase-1) in osteoarthritic chondrocytes. FEBS Letters. 2008;582:2945–2949. doi: 10.1016/j.febslet.2008.07.036.

Troeberg L, Fushimi K, Khokha R, Emonard H, Ghosh P, Nagase H. Calcium pentosan polysulfate is a multifaceted exosite inhibitor of aggrecanases. FASEB J. 2008;22:3515–3524. doi: 10.1096/fj.08-112680. 

Munteanu SE1, Ilic MZ, Handley CJ. Calcium pentosan polysulfate inhibits the catabolism of aggrecan in articular cartilage explant cultures. Arthritis Rheum. 2000 Oct;43(10):2211-8.

Guangyong Ma, Jun-ichirou Yasunaga, Koichi Ohshima, Tadashi Matsumoto, Masao Matsuoka. Pentosan Polysulfate Demonstrates Anti-human T-Cell Leukemia Virus Type 1 Activities In Vitro and In Vivo. 
 
Lara J. Herrero, Suan-Sin Foo, Kuo-Ching Sheng, Weiqiang Chen, Mark R. Forwood, RichardBucala, Suresh Mahalingam. Pentosan Polysulfate: a Novel Glycosaminoglycan-Like Molecule for Effective Treatment of Alphavirus-Induced Cartilage Destruction and Inflammatory Disease.