Paradigm Biopharmaceuticals Ltd (ASX:PAR) has highlighted the online publication of a preclinical study investigating the anti-inflammatory and arthritic disease-modifying effects of pentosan polysulfate sodium (PPS) in the mouse model of the alphavirus chikungunga (CHIKV) induced arthralgia in scientific peer-review journal, PLoS ONE.
The demonstration that PPS can improve strength, swelling and inflammation in the CHIKV preclinical model supports further clinical evaluation of PPS as a potential disease-modifying therapy for CHIKV-induced arthralgia.
This comes on the back of promising clinical outcomes of improved pain and function in subjects in Paradigm’s Phase 2A Ross River virus (RRV) pilot clinical trial.
The study 'Pentosan polysulfate sodium prevents functional decline in chikungunya infected mice by modulating growth factor signalling and lymphocyte activation' was undertaken at Griffith University’s, Institute for Glycomics by principal investigator and corresponding author of the publication, Dr Lara Herrero.
Scientific support
Paradigm chief scientific officer Dr Ravi Krishnan said: “Our recent preclinical data in the CHIKV mouse model has provided scientific support for the potential of PPS to treat debilitating symptoms associated with long term CHIKV infection.
“Therefore, to establish the clinical efficacy and safety of PPS in alphavirus-induced arthralgia following Paradigm’s completed Phase 2A clinical trial in RRV-induced arthralgia, a larger clinical trial involving CHIKV infection, which has a higher global prevalence is warranted.”
Potential world-first CHIKV therapy
Principal investigator and corresponding author Dr Lara Herrero said: “Our foundational preclinical studies demonstrate that PPS not only improves the inflammation/arthritis that ensues after infection but also improves limb function with mice showing improvements in grip strength.
“As joint pain and loss of limb strength are common aspects of CHIKV-induced disease, these critical findings provide confidence in PPS as a potential world-first CHIKV therapy.
“With no vaccines or specific therapeutics to prevent/treat alpha viral-induced arthralgia, the results of our study gives hope to millions suffering with alpha-viral arthritis globally.”
Details of study
Data reported in the preclinical study showed objective measures of functional improvement as measured by grip strength, which was supported by the reduction in inflammatory cells in the joints of animals treated with PPS.
Chemokines CXCL1, MCP1, MCP-3 and MCP-5 that are involved in immune cell infiltration of the joint, showed statistically significant reduction in serum levels because of PPS treatment.
The anti-inflammatory effect of PPS was demonstrated by statistically significant reduction in the swelling of the foot joint compared to untreated CHIKV infected animals.
The global gene expression analysis of the local joint demonstrated that the actions of PPS were related to the regulation of genes involved in growth factor signalling and lymphocyte activation.
Chikungunya virus
CHIKV is closely related to the Ross River virus (both of the alphavirus genera) and causes similar debilitating symptoms of joint pain, fever, headache, conjunctivitis and rash.
Outbreaks have been reported in parts of Africa, Europe, Southeast Asia and islands in the Indian and Pacific Oceans.
In 2013, CHIKV was found for the first time in the Americas and has spread to the Caribbean as well as South and Central America.
The lack of anti-viral agents, vaccines or effective pharmaceutical agents to treat the debilitating effects of CHIKV make iPPS a potentially valuable product for this unmet medical need.