In a study of how particular enzymes in the immune system control cell activation and movement, Dr Iain Comerford from the University’s School of Molecular and Biomedical Science, colleague Professor Shaun McColl and two PhD students focused on a molecule called PI3Kgamma.
“There’s already been worldwide interest in PI3Kgamma in relation to other human inflammatory disorders, such as diabetes and rheumatoid arthritis, and our study links this molecule and MS,” said Dr Comerford, who completed his research during a three year Multiple Sclerosis Research Australia fellowship.
The University of Adelaide study, published recently in the online journal PLOS ONE, showed that when a genetic alteration stopped PI3Kgamma, nerve cells showed a high level of resistance to experimental autoimmune encephalitis (EAE), which is an animal model developed for laboratory work to study MS.
The findings suggest that the nerve system would be protected against the forms of damage typically caused by MS.
When the molecule PI3Kgamma was present, researchers found evidence of severe damage to the myelin which insulates the nerve fibre (axion) of a nerve cell. This damage caused myelin loss and spinal cord inflammation.
The research team followed these results by using a drug which blocks activity of PI3Kgamma at the earliest indications of disease onset. The drug was found to block the development of EAE and clinical signs of the disease were reversed.
Calling the results very promising, Dr Comerford said, “We’ve shown that by blocking PI3Kgamma, we can reduce the activation of self-reactive immune cells, reduce the release of inflammation-inducing molecules from immune cells, and also result in a dramatic reduction in the movement of immune cells into the central nervous system.
“Our hope is that future therapies for MS might target this molecule, which could very specifically dampen the damaging inflammation in the central nervous system.
“It will now be crucial to determine whether targeting these molecules could be a safe and effective way to treat MS in humans.”
Multiple sclerosis is incurable at present. This inflammatory disease causes the myelin sheathes around the axions of nerve cells in the brain and spinal cord to become scarred or reduce. The results can cause a wide range of symptoms for sufferers of the condition. The degree to which those symptoms impact on the patient’s life also varies over time.