Developing Cell Therapy for Childhood Neurodegeneration

At Great Ormond Street Hospital, we look after children with devastating diseases affecting the brain. Unfortunately, for most affected patients, there are currently no treatments that can prevent disease progression leading to premature death in childhood. Some of our patients have diseases caused by the loss of specialized brain cells called “neurons”. A number of genetic and environmental factors can lead to the death of these neurons, which are then lost as a consequence of a process called “neurodegeneration”. Unfortunately, this process is irreversible as neurons cannot be naturally replenished in the same way as other body tissues. Cell therapy approach to treat childhood disease presenting neurodegeneration. Over the last few decades, researchers have developed methods of generating human brain cells from patient’s skin cells, which ideally allows the production of new and healthy cells to replace the ones missing or malfunctioning in a specific disease, using a therapeutic approach called “cell therapy”. Until recently, the standard clinical approach has been transplantation to replace diseased organs or cells, which is highly dependent on availability of donors and the donation of brain cells is currently not possible. Therefore, the generation of brain cells in a laboratory setting allows the development of new therapeutic approaches that aim to replace those lost through neurodegeneration. Currently there are some clinical trials looking into cell therapy as a treatment for Parkinson's Disease (currently the 2nd most common neurodegenerative disorder affecting the world population). However, these trials do not evaluate using cell therapy in children with neurodegenerative disorders. Proposed project’s goals. Our long-term goal is to develop a novel cell therapy approach for progressive neurological conditions in children collectively known as ‘childhood neurodegeneration’. The aim of our project is therefore to perform studies in a laboratory model of childhood neurodegeneration to test the potential of cell-based therapy for this group of disorders. We have already performed some preliminary studies in an animal model of childhood neurodegeneration and showed the feasibility of this approach to rescue the disease progression. In this project, we now aim to test our approach transplanting the created neural cells in the animal brain, using a process similar to the one that will be used in patients, to see if these transplanted neural cells replace the damaged neuronal cells. We will also evaluate the dose of the neural cells needed and if there are any side effects from the neural cells. The information we get from this study will then help us to develop the therapy further towards clinical application for childhood neurodegeneration. This project will enable us and other researchers to look into therapies for childhood neurodegeneration and may shorten the time it takes to get these therapies to patients. We hope to provide a single disease-modifying therapy with neural cell therapy that will reduce the risk of mortality, prevent disease progression and improve quality of life for the patients and their families.