Researchers studying drugs prescribed for brain-related conditions have found that administering a lower dose could potentially treat diseases such as Alzheimer’s and Parkinson’s.
In a study led by Dr Daniel Sillence, a reader in cell biology at De Montfort University Leicester (DMU), researchers identified new insights into Niemann-Pick C disease (NPC), a rare condition which is also referred to as ‘childhood Alzheimer’s’.
Dr Sillence and his team at the Leicester School of Pharmacy examined the effects of a drug used to treat NPC, called Miglustat, by trialling a lower dose on NPC cells.
“Over the last four years we have been testing imino sugar drugs that are already being used to treat rare neurodegenerative conditions,” explained Dr Sillence.
Testing skin cells taken from NPC patients, the team administered 6mg rather than 600mg, which is the standard daily dose prescribed to those with the condition.
“The primary target of these drugs is to prevent the accumulation of cholesterol and other fatty substances (known as glycolipids) in the brain, which cause neurodegeneration,” said Dr Silence. “However we have identified a new target for these drugs.”
The accumulation of lipids in brain tissue is caused by a defect in a lysosomal enzyme (the cell’s recycling centre). This new research conducted at DMU indicates that the defect can in fact be corrected and reversed with a much smaller dose of the medicine.
“This is really important as it suggests that these drugs have a much broader utility than what they are currently being used for,” said Dr Sillence. “We believe they could potentially be rapidly developed for treating related diseases including Alzheimer’s and Parkinson’s.”
Alzheimer’s disease contributes to around 60-70% of all cases of dementia. There are around 50 million people living with dementia worldwide and nearly 10 million new cases are diagnosed every year.
It is thought 1 in 500 people are affected by Parkinson’s, with men more likely to get the disease than women. Between seven and 10 million people are diagnosed with Parkinson’s worldwide.
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Dr Sillence added: “There are therapies trying to do exactly what we’ve found that these drugs can already do at low dose. And because Miglustat has approval from the EMA (European Medicines Agency), we know it is safe to use.
“This research could have a major impact on patients with common neurodegenerative conditions. It could decrease cognitive decline and ultimately improve their lifespan.”
A reader in cell biology, Dr Sillence attained his PhD in biochemistry at Dundee University in 1992. He joined DMU in 2007, having previously taught at the University of Oxford.
His latest papers, ‘Lipid–Protein Interactions in Niemann–Pick Type C Disease: Insights from Molecular Modeling’ and ‘Cytosolic Glucosylceramide Regulates Endolysosomal Function in Niemann-Pick Type C Disease’ have been published in two leading journals - Neurobiology of Disease and the International Journal of Molecular Sciences.
Posted on Monday 15th April 2019