Gene-based therapies paving the way for the treatment of Alzheimer’s Disease
Neurological researchers are investigating the benefits of using advanced gene-therapies to treat people with Alzheimer’s Disease. A worldwide clinical research trial is currently underway, supported by dedicated researchers at The University of Sheffield.
Neurological researchers are investigating the benefits of using advanced gene-therapies to treat people with Alzheimer’s Disease. A worldwide clinical research trial is currently underway, developed by IONIS pharmaceuticals in collaboration with scientists at Washington University and supported by dedicated researchers at The University of Sheffield. The trial is based on successful results from preclinical tests, which showed that antisense oligonucleotide therapies (ASO) effectively reduced symptoms and behaviours of the disease. This could potentially significantly improve the quality of life of patients.
This study investigates the use of ASO gene-based therapies aimed at treating Alzheimer’s Disease as an alternative to current medications. At present, medications called cholinesterase inhibitors are prescribed for mild to moderate Alzheimer’s disease but these do not target the main cause of the disease and can only slow progression temporarily. For patients with moderate to severe Alzheimer’s, an N-methyl D-aspartate (NMDA) antagonist is usually prescribed.
This ASO trial offers a promising alternative to current medications by targeting the source of the disease within DNA rather than treating the symptoms and behaviours. This occurs because the ASO drug causes proteins to work in different ways by binding small pieces of DNA or RNA to specific molecules of RNA. The drug subsequently either blocks production of proteins needed for cell growth - triggering degradation in troublesome genes, or enhances the expression of a needed gene to improve clinical outcomes.
Findings have shown a reduction in toxin-induced seizures, neuronal loss, and neurofibrillary pathology. Positive signs of normalized behavioural phenotypes (patterns that typify characteristics of a neurological disorder) and survival length is also evident.
Having recently undergone ethical approval to trial this new therapy on patients with Alzheimer’s Disease, these advanced therapies are now being used in clinical settings; including here at The University of Sheffield. A total of 44 participants across Canada and Europe aged 50-74, with mild AD have been enrolled in a 13-week, multiple-ascending-dose study of monthly injections.
Of these, five participants were recruited from Sheffield and entered a 12-month period extension study overseen by Daniel Blackburn, Senior Lecturer and Honorary Consultant Neurologist at The University of Sheffield.
The data from this initial 12 month study is currently being analysed. It is expected that next year the university will work in collaboration with an industrial partner to conduct a phase 2 study to determine efficacy.
