Dr Christine Pham, a rheumatologist at the Washington University School of Medicine, is designing strategies to safely deliver nanomedicine in the treatment of inflammatory diseases, such as arthritis. Her strategies promise to target pathways associated with inflammation, while leaving other vital immune responses unaffected.
Rheumatoid arthritis (RA) is a chronic, incapacitating disease of the joints, characterised by painful swelling and progressive damage to the connective tissues affected. This is a major cause of disability and morbidity (the condition of being diseased), particularly in ageing populations. Although the underlying causes remain the subject of debate among researchers and clinicians, the symptoms are clear and well-documented.
Crippling pain
An influx of immune cells from the bloodstream leads to swelling and inflammation of the synovial lining of the joints (the membrane that defines the joint space and retains the lubricating synovial fluid). This promotes the release of inflammatory molecules and degradative enzymes, resulting in damage to the connective tissue and the underlying bone of the joint in a vicious cycle that is painful and debilitating to the sufferer.
Although there are several treatment options for RA sufferers, the therapy is often associated with severe adverse effects and is ineffective in a large segment of the patient population. Dr Pham leads her team in investigating alternative treatment options, targeting the inflammation that underlies the pathogenesis of rheumatoid arthritis and other inflammatory conditions.
Interfering with RNA
RNA interference (RNAi) is a relatively new technique for preventing the DNA that encodes specific genes from being transcribed and translated into proteins. In the normal process, DNA is first transcribed into messenger RNA (mRNA), which can be translated into proteins by the cellular machinery. In mammalian cells, this is a carefully orchestrated process that controls a multitude of cellular activities and protects against hijacking of the cellular machinery by viruses. RNAi techniques exploit intrinsic cell mechanisms to ‘silence’ a gene by delivering small interfering RNA (siRNA) that binds to complementary strands of mRNA, promoting their degradation and blocking protein production.
Illustration Credit: iStock
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