Early results with active immunotherapy were the focus of a late-breaking presentation from Dr Bjoern Sperling, of H. Lundbeck A/S, Valby, Denmark. Active immunotherapies have the potential to use immune systems memory cells to start production of specific antibodies against the amyloid protein when it groups together to form the so-called amyloid plaques in the brains of people with Alzheimer’s disease, said Dr Sperling.
The accumulation of Aβ plaques in the brain occurs early in the disease process, and intervention at an early stage of disease is a therapeutic goal in Alzheimer’s disease.1 A reduction in Aβ levels in the brain might be achieved by the reduced formation of oligomers and plaques by inhibition of Aβ aggregation or through reduction in Aβ levels by increased degradation and clearance.
An active immunotherapy approach has been tested in animal models of Alzheimer’s disease, which shows a fast response in - ‘non-self’ T-cell inducing a production of highly specific anti-Aβ antibodies that reduce Alzheimer’s disease-pathology. A single dose induced strong humoral immunity in mice with pre-existing memory T-helper cells2, cells that most people also have preserved from their childhood vaccinations.
Active immunotherapies have the potential to induce anti-Aβ antibody responses in patients with Alzheimer’s disease while reducing risk of severe adverse events by not inducing autoreactive T-cell responses.2 This approach may result in clearing of aggregated forms of Aβ species and prevention of nerve cell dysfunction or death.
Active immunotherapies have the potential to induce anti-Aβ antibody responses in patients in the eary stage of Alzheimer’s disease
Early investigations have explored the safety of active immunotherapy in patients with mild Alzheimer’s disease.3 The efficacy of this approach is yet to be demonstrated in larger clinical trials designed to evaluate efficacy based on change in brain amyloid load, and impact on cognitive, functional, and behavioral impairment.
If successful, immunotherapy could be a key and basic part of any future combination therapies for Alzheimer’s disease in the future. It is likely that an anti-amyloid treatment will be needed to remove or reduce aggregated Aβ together with other disease-modifying and symptom-reducing therapies.4
Active immunotherapy as an approach to reducing tau pathology is also under preliminary investigation.5 As well as the accumulation of Aβ around neurons, Alzheimer’s disease is characterized by the aggregation of microtubule-associated protein tau into neurofibrillary tangles.
This article provides highlights from H. Lundbeck A/S late-breaking presentation at CTAD