Glial dysfunction in multiple forms of NCL: new directions for therapy

Lead Researcher:

Dr Jonathan Cooper

Award Date:

1 January 2012

Host Institution:

King's College London

Scheme:

MRCG-HRB Joint Funding Scheme

Summary:

The neuronal ceroid lipofuscinoses (NCLs or Batten disease) are a group of inherited diseases that kill children. These diseases, which come in several different types, are caused by mistakes in particular genes. The end result is devastating upon the child’s brain, but it is not clear exactly how this happens. When investigating this, we have found that it is not just the nerve cells that are affected. Instead, populations of glial support cells, that help them function properly, are actually the first cells to be targeted by disease. Our work so far in the relatively common juvenile NCL reveals that glia are themselves fundamentally sick and do not function properly. We have found that these sick glia have harmful effects upon nerve cells, and that these can be reversed by replacing them with healthy glia. Everything points to these cells being important in the other major forms of NCL, and we shall now use the same methods to investigate this and whether this novel therapeutic approach of correcting glial defects may also be useful in infantile and late infantile NCL.
If this is ever to become a new way to treat this fatal disease, we must investigate glial biology in the living brain to find out more about how the normal communication between glia and nerve cells is disrupted. We will then test the idea that what we have found in a dish will also work in a living brain by causing or ‘switching off’ the disease just in glia and seeing how this affects the normal course of the disease. All of this information will be crucial for designing effective therapies to correct glial defects and provide some hope for children who will otherwise die.