Gene therapy research in Type 2 Gaucher disease

The Gauchers Association has awarded a grant from funds raised by the Eleanor Lily Foundation to The Royal Free Hospital in London to purchase a batch of viral vectors for use in their gene therapy research in Type II Gaucher disease. Simon Waddington, a Senior Research Fellow in the Department of Haematology at the Royal Free Hospital in London describes the work being carried out –

‘To date, therapeutic efforts towards treatment of Type 2 – or neuronopathic – Gaucher disease remain without reward. It has proved impossible to prevent or reverse the most lethal aspect of this disease, which is the damage it does to the brain’.

‘Gene therapy is one of several options that researchers are exploring and which might, one day, provide a form of treatment for this disease. Gene therapy is a relatively new field of medicine where genes, rather than proteins or drugs, are delivered to the damaged cells and tissues to provide a very long-lasting treatment. However, an obstacle to the treatment of neuronopathic Gaucher disease is that the gene delivery vehicles (‘vectors’) have  not been able to pass from the bloodstream into the brain’.

‘Here at the Royal Free, our expertise lies in the very early treatment of mouse models of genetic diseases using gene therapy, and we collaborate with obstetricians at University College London and at Imperial College. We were able to inject genes into foetal mice to cure a model of haemophilia B, and since then, we have been exploring how we might use this technology for more serious and incurable diseases. We decided that a good target would be Type 2 Gaucher disease so we have been developing gene therapy vectors – the vehicles used to deliver the genes – and have seen long-lasting expressions of marker genes after injection into the brains of foetal mice. We have received a mouse model of Type 2 Gaucher disease from Professor Stefan Karlsson in Sweden and aim to try to cure these mice by delivering glucocerebrosidase to their brains by in utero gene therapy’.

‘Recently, a paper was published showing that a very specific gene therapy vector, called ‘AAV9’ can deliver genes to the brain of adult and neonatal mice after intravenous injection. This is very exciting as intravenous injection is much more clinically acceptable than direct injection into the brain and we would like to confirm these results and improve upon them by injecting them into the circulation of foetal mice. If this works, we would like to use this vector and injection route to attempt to cure the Type 2 Gaucher mice by in utero gene therapy. The most expedient way of getting very good quality AAV9 is by buying it from an academic ‘core’ facility in the United States. A batch would be sufficient for us to complete all the preliminary experiments on in utero brain targeting (we will inject them while they are still in the womb as we have done previously with other mouse models)’.

‘We are extremely grateful to the Gauchers Association and the family of Ellie Carter who have given us a grant to purchase a batch of these vectors to support our work. Ellie Carter died in 2004 aged seven months from Type 2 Gaucher disease. In memory of Ellie, her parents Jill and Ian, set up ELF, the Eleanor Lily Foundation, to raise funds to go towards research into understanding more about Type 2 Gaucher disease’.