A vaccine that trains the body to attack the toxic protein clumps behind Parkinson’s disease has passed its first major test, with every participant who received it developing antibodies against the target in an early Phase 2 trial.
The first part of the study involved 34 people with early-stage Parkinson’s disease. Of these, 25 received ACI-7104 and nine received a placebo.
All participants who received the vaccine developed antibodies against its alpha-synuclein target after three immunisations by week 100.
ACI-7104 is being developed by AC Immune as an active immunotherapy designed to train the immune system to produce antibodies against a disease-related target.
Günther Staffler, executive vice president of development at AC Immune, said: “We are pleased to have observed strong and boostable immune responses, with significant antibody penetration into the CSF and signals for target engagement.”
He added: “Together with the favourable safety profile … and exploratory correlations between antibody titers and disease activity measures, we are confident that these results provide a strong foundation for the continued development of ACI-7104 into Part 2.”
Alpha-synuclein is a protein that can misfold and form abnormal clumps in nerve cells in Parkinson’s disease. Smaller structures called oligomers are thought to be the main drivers of nerve damage and inflammation.
The vaccine contains a laboratory-made small protein that mimics part of alpha-synuclein. It is intended to generate antibodies that preferentially recognise aggregated forms of the protein, particularly toxic oligomers, while sparing normal single molecules.
Participants in the first part of the VacSYn study had a mean age of 62.1 years and 65 per cent were men. They received ACI-7104 or placebo as intramuscular injections at predefined intervals over 74 weeks.
The company said the study met its primary goals for safety, tolerability and immunogenicity, or the ability to generate an antibody response to the vaccine’s target.
Most side effects were transient and generally mild. Injection-site reactions were reported in 55.9 per cent of participants, followed by fatigue, headache and common cold.
AC Immune said all primary endpoints were met, with strong immunogenicity and a 100 per cent response rate at week 100.
Antibodies generated by the vaccine were also detected in cerebrospinal fluid, the fluid surrounding the brain and spinal cord, with levels increasing after additional doses.
Preliminary analysis indicated that the antibodies engaged aggregated alpha-synuclein in the cerebrospinal fluid. Levels of neurofilament light chain, a biomarker of nerve damage, remained stable.
Exploratory analyses suggested associations between antibody levels and measures of disease activity.
The trial is continuing and advancing towards a second part designed to gather clinical proof-of-concept data and monitor Parkinson’s symptoms alongside digital, imaging and fluid biomarkers.
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