Motor neurone death in MND is associated with an inflammatory response. This recruitment of immune cells is a necessary part of the "clean up" of dying cells. Without this immune response dying neurones would become toxic to neighbouring cells. However, the immune response can become toxic to the very cells it is protecting, and prolonged inflammation in the brain can be detrimental. It is known that MND patients have an increased level of an immune signaling molecule called MCP-1. This, like the bat signal that attracts Gotham's defender, attracts immune cells to the source of the signal. A study recently published by Pamela Shaw's research group at the University of Sheffield, UK has shown that a particular immune cell in the brain, microglia, can express 3 times as much of this MCP-1 signal when it carries the mutation in SOD1 in the test tube. This may mean that people carrying the mutation are more likely to have an inappropriately increased immune response to certain insults.
Out of a collaboration of Professor Don Cleveland and Professor Beroslav Zlokovic's laboratories in the USA has come research that suggests that treatment with activated protein C therapy can substantially prolong the life span of mutant SOD1 MND mice. The researchers say that this treatment works at the most fundamental level by reducing the levels of the SOD1 in motor neurones and importantly by acting on the brains immune cells. The treatment was able to lower immune signalling of MCP-1 and thus lowered the amount of inflammation in the brain. This drug is already in use for other purposes and so is a promising lead for mutant SOD1 carriers.
Although we just looked at the over-active immune system being harmful, some researchers think that recruiting certain arms of the immune system may prove beneficial. A research team led by Yuanjin Zhang in Beijing, China has used G-CSF (an specific immune stimulator) in a clinical trial of 13 MND patients. The study shows that there are mild side effects to the treatment such as fever or infection-like symptoms. The report also suggests that the patients did not decline faster after the treatment, in fact they may have declined slower over the 6 months after treatment. Caution must be used when interpreting data such as this, since not all patients have a consistent linear progression. Further clinical trials are required to definitively demonstrate any positive outcomes.
Source: International MND research update -December 2009, Dr Justin Yerbury for MNDRIA