Developments in immunotherapies for Parkinson’s: new data on BIIB054
Original article: Development of an aggregate-selective, human-derived α-synuclein antibody BIIB054 that ameliorates disease phenotypes in Parkinson’s disease models, Neurobiology of disease: October 28, 2018.
The takeaway
BIIB054 is an antibody which is highly selective for the toxic, misfolded form of alpha-synuclein. Preclinical studies have shown BIIB054 reduces the spread of misfolded alpha-synuclein, and limits the damage it normally does to neurons.
Why is it important?
This work demonstrates the potential of BIIB054 as a highly selective immunotherapy which could potentially modify the course of Parkinson’s, and place more useful data on this antibody in the public domain for further evaluation.
%
IMPACT
- Novelty 65%
- Proximity 70%
- Deliverability 70%
Impact Opinion
“Immunotherapy is not only an experimental therapy which has the potential to revolutionise the treatment of Parkinson’s, but also to answer a fundamental question regarding our basic understanding of Parkinson’s: Is aggregated alpha-synuclein involved in the progression of Parkinson’s? By removing the aggregated form of this protein, can we halt the rate of neurodegeneration? If yes, then future generations will have an extremely powerful treating for dealing with this condition before it develops to far. If no, then we will need to rethink many of our current ideas about PD. This report is very encouraging, as large pharmaceutical companies are usually reluctant to share their preclinical data in order to protect their intellectual property. Biogen should be applauded for publishing this report.”
Background
Alpha-synuclein is a protein which is abundant in the brain and throughout the body. It carries important functions, in relation to communication between neurons for example. When misfolded however, it becomes toxic to neurons and is a believed to be a key pathological agent in Parkinson’s. It is therefore a key target for disease modification. Immunotherapies attempt to use immune cells, and specifically the antibodies that they generate, to target alpha-synuclein and inactivate it. What is the latest in these efforts?
The details
The researchers first derived the antibodies which bind to alpha-synuclein, from cloned B lymphocytes, which are a specific type of white blood cell obtained from healthy elderly donors. These specific BIIB054 antibodies were selected on the basis of their ability to bind toxic, misfolded alpha-synuclein found in postmortem brain samples obtained from individuals with Parkinson’s and Lewy Body Dementia. Having established this high selectivity, BIIB054 antibodies were taken through to a series of animal experiments. The researchers first produced misfolded alpha-synuclein. Then, they infused the animals with BIIB054 or a control, ineffective antibody. After BIIB054 infusions were begun, the misfolded alpha-synuclein was injected directly into the striatum, a key region of the brain involved in movement. They found that BIIB054 administered weekly, significantly delayed the onset of movement symptoms. The researchers then asked whether BIIB054 can stop the spread of alpha-synuclein between adjacent neurons. Prior and continuous administration of BIIB054 caused a significant reduction in the overall amount of misfolded alpha-synuclein found in these animals and also improved some of the movement problems. They also found that BIIB054 reduced the loss of dopamine transporters (DAT) – a mechanism by which dopamine is recycled in the brain, normally found on dopamine neurons and measured by DAT scans. A reduction in the loss of DAT indicates survival of functioning dopamine neurons.
Next steps
A multicenter Phase 2 clinical trial has begun recruiting individuals with early stage Parkinson’s, to evaluate BIIB054.
Related work
- https://www.thesparkstudy.com/
- https://www.thesparkstudy.com/en-us/clinical-studies.html
- https://clinicaltrials.gov/ct2/show/NCT03318523
Where can I learn more?
Previous BIIB054 clinical trial
https://clinicaltrials.gov/ct2/show/NCT02459886
Brundin, P., K.D. Dave, and J.H. Kordower. 2017. Therapeutic approaches to target alpha-synuclein pathology. Exp Neurol. 298:225-235
https://www.ncbi.nlm.nih.gov/pubmed/28987463
See also stories on alpha-synuclein vaccine:
Original article: Development of an aggregate-selective, human-derived α-synuclein antibody BIIB054 that ameliorates disease phenotypes in Parkinson’s disease models, Neurobiology of disease: October 28, 2018.
