ɑ-Synuclein is a protein found abundantly in the brain. It is involved in a variety of normal brain functions. However, as we get older and age, ɑ-synuclein can form clumps (aggregates) inside brain cells (neurons). These a-synuclein aggregates cause neurons to die in a process called neurodegeneration, and this may trigger Parkinson’s disease (PD). PD is an age-related movement disorder most commonly affecting people over 60 years of age. New scientific research into what causes PD has shown that ɑ-synuclein aggregates can be released from sick or dying neurons and then taken up into nearby healthy neurons. Once inside the healthy neurons, a-synuclein aggregates start to damage them too and they eventually die. It is thought that this a-synuclein aggregate “spreading” process self-propagates throughout nerve cell networks causing neurodegeneration in affected brain regions. One brain region commonly affected by a-synuclein aggregates in PD is called the substantia nigra, which is involved in controlling movement. We know that when around 80% or more of the neurons in the substantia nigra have degenerated (died) in a process believed to be driven by neurotoxic a-synuclein aggregates, people experience shaking, slowness of movements and find it difficult to walk around. There are currently no treatments or therapies available to prevent or slow the neurodegeneration in PD.
Scientists have developed experimental pre-clinical models of a-synuclein spreading and neurodegeneration that are now providing important new insights into how spreading may cause neurodegeneration and how it can be stopped. These PD spreading models are being utilised in drug discovery efforts. Antibodies that bind to a-synuclein have been shown to prevent a-synuclein spreading throughout the brain. a-Synuclein antibodies have potential to become an important new class of disease-modifying drug treatment for PD. AstraZeneca have developed a high affinity ɑ-synuclein-specific antibody called MEDI1341 that strongly reduces a-synuclein spreading in an pre-clinical PD model. We recently entered into a collaborative agreement with Takeda Pharmaceuticals to jointly develop MEDI1341 as a potential novel PD therapy, and it is currently in early clinical Phase I testing.