New Treatment for Chronic Granulomatous Disorder (CGD)

Chronic Granulomatous Disorder (CGD) is a genetically inherited severe immune deficiency that effects one in 200 000 people per year worldwide. Its sufferers have a reduced ability to fight off infection and because of the inherited nature of the disorder and the severity of the consequences many die at a young age. This is predominantly an illness that effects children and young people.

Children with CGD often suffer life threatening infections and one of the worst is infection with Aspergillus. Aspergillus is able to infection people with normal immune systems who have damaged lungs but those infections are usually limited to the site of infection and can sometimes be removed surgically with good results. CGD patients cannot limit the spread of Aspergillus as efficiently as non-CGD people as their immune system is weaker, so once Aspergillus infects a CGD patients it is much more difficult to prevent it spreading. CGD patients have to be treated more often with antifungal medication.

New research has found a new method to treat CGD patients. One of the ways that the immune system of a CGD patients does not work properly is in the production of reactive chemicals by specific immune cells (neutrophils) that are used to kill invading microbes. It has also been found that neutrophils also respond to infection by forming a structure called a Neutrophil Extracellular Trap (NET). These literally form a network of fibres rather like a spiders web that trap microbes and then exude reactive chemicals to kill microbes once trapped. One of the chemicals produced is calprotectin which has antifungal properties and this research has pinpointed that calprotectin is important in the battle against Aspergillus infection. Neutrophils from CGD patients cannot form NET's or produce calprotectin.

How do we treat this absence of calprotectin in CGD patients? Bianchi used gene therapy techniques to restore the ability of CGD neutrophils to produce calprotectin and found that they were also able to form NETs and successfully fight off a pre-existing Aspergillus infection in human patients. This patient already had a life threatening infection prior to treating with gene therapy. Gene therapy effectively 'cured' some of the immune deficiency and the restored immune system was successful in defeating the aspergillosis.

This extraordinary result implies that gene therapy now has the potential to be a routine treatment for aspergillosis in CGD patients - it can be used when there is an ongoing infection. In practice this treatment is only being recommended for use in infections where antifungal therapy is ineffective as the current method involves the use of a DNA construct based on a disabled virus. This virus is presumably infected into neutrophils (details of exactly how this has been done had eluded me) and there are risks associated with that strategy. Until more is known about those risks gene therapy will be used with caution.

This research has been supported by Chronic Granulomatous Disorder Research Trust, United