Our research focusses on cytoplasmic glycolipids which we believe are important regulators of lysosomal function. Glycolipid imino sugar inhibitors (eg Miglustat) are currently used for the treatment of neurodegenerative diseases such as Gaucher and Niemann-Pick C. However acting on a different target these inhibitors have now been shown to correct defective lysosomal acidification which is also thought important in Parkinson’s and Alzheimer’s. This work was recently published.
Brain diseases caused by the accumulation of glycolipids (fatty substances) in tissues are known as glycolipid (GSL) storage diseases. The build-up of glycolipids is caused by a defect in their breakdown within the lysosome (the cell’s recycling centre) and our latest research indicates that we can reverse that defect when treating patients with GSL diseases. Although rare, there are around 40 different types of these diseases that we are aware of, and they can affect people of all ages. More common brain conditions, including Alzheimer’s and Parkinson’s, are related to GSL diseases, as they too may have defective lysosomal acidity. For our latest study, we looked at Niemann-Pick C disease (NPC); a condition that affects the body’s ability to metabolise fat within cells, which eventually causes the cells to malfunction and die. People with NPC suffer progressive dementia and loss of brain function and other organs, and the condition mainly affects children - hence why we call it ‘childhood Alzheimer’s’.
To slow down the disease, patients are currently prescribed a 600mg daily dose of imino sugar called Miglustat, which is intended to reduce the build-up of glycolipids in the brain tissue. However, the effectiveness of the 600mg dose has come into question in recent years, as new studies show that as well as reducing the targeted glycolipids, the drug is actually causing an increase in another specific type of glycolipid, outside of the lysosome. What this means is that the original targeted defect is not corrected as hoped but rather ‘balanced out’. This is why our findings are so important.
By lowering the daily dose by 100 to just 6mg, we have identified a new target for Miglustat which enables us to reverse the defect in the lysosome without affecting any other type of glycolipid. So little is known about all forms of brain disease but our findings will help determine the way in which these already-approved drugs can be used, as we begin to understand more about other glycolipid diseases and related conditions.
Read about the research on express.co.uk