Potential of Vaccines in Treating Parkinson’s, Alzheimer’s Detailed
AC Immune planning Phase 2 trial of ACI-7104 vaccine in early-stage Parkinson's
In a webinar hosted by AC Immune, scientists discussed the various advantages of vaccines — ranging from their expected safety and long-lasting immune responses to potentially lower costs — in treating and possibly preventing Parkinson’s and Alzheimer’s disease.
The “Key Opinion Leader” webinar, broadcasted on Aug. 24 and available for viewing, offered a presentation by Cynthia A. Lemere, PhD, a scientist at the Ann Romney Center for Neurologic Diseases at Brigham & Women’s Hospital and an associate professor of neurology at the Harvard Medical School. Lemere also works as a scientific advisor and consultant for AC Immune, among other companies.
Vaccines are a form of active immunotherapy for neurodegenerative diseases, which work by stimulating the immune system to produce antibodies against the abnormal, or misfolded, proteins driving these diseases. In the case of Parkinson’s, clumps of the misfolded alpha-synuclein protein spread throughout the brain and contribute to nerve cell death and disease progression.
AC Immune is planning to open a Phase 2 clinical trial of ACI-7104, a potential vaccine against the toxic alpha-synuclein protein in Parkinson’s patients this year.
A newer generation of vaccines, called multi-epitope vaccines, target several epitopes — the part of a protein that elicits an immune response — on misfolded proteins. As such, they are designed to elicit a more powerful immune response, AC Immune reported in an accompanying company press release. Multi-epitope vaccines also contain adjuvants, additional components that boost immune responses.
Question of ‘balancing safety and efficacy’
Vaccines are designed to provide long-lasting immune activation, the speakers stated, leading to a consistent and gradual production of antibodies against misfolded protein clumps. This allows for greater safety and long-term efficacy than is possible with synthetic or lab-made monoclonal antibodies that only target one epitope. Monoclonal antibody treatment, the scientists explained, is a passive immunotherapy, with a relatively short-lived peak in antibody production compared with vaccines.
“It’s really a question of balancing efficacy and safety,” Lemere said, speaking of monoclonal antibodies in studies for Alzheimer’s disease relative to potential vaccines.
Vaccines also enhance a person’s own immune response. “Active vaccination is a way to have the body basically make antibodies,” Lemere said.
Vaccines can be administered as “a simple injection,” she added, while monoclonal antibodies are often infused over four hours during regularly scheduled hospital or clinic visits. They also can be cost-saving and less of a burden to patients, needing to be given possibly only once or twice a year, she added.
Contrary to monoclonal antibodies, however, the immune response triggered by vaccines cannot be shut down.
“The ability of vaccines to safely and specifically target multiple epitopes on the toxic drivers of neurodegenerative disease makes them uniquely suited to address the unmet needs of patients,” Lemere said in the release. “Data from prior clinical studies conducted by AC Immune and others clearly highlight the therapeutic potential of vaccines and provide a strong scientific rationale for the Company’s ongoing and planned trials.”
Marie Kosco-Vilbois, PhD, chief scientific officer at AC Immune, and Johannes Streffer, MD, the company’s chief medical officer, also spoke at the event. They presented an overview of the company’s goals and pipeline of candidate vaccines.
Phase 2 vaccine trial in early-stage Parkinson’s expected to soon start
ACI-7104, its lead candidate for Parkinson’s and other synucleinopathies, diseases characterized by the accumulation of misfolded alpha-synuclein aggregates, was initially developed by Affiris and later acquired by AC Immune. It is designed to trigger a specific immune response against toxic aggregates of alpha-synuclein.
A Phase 1 clinical trial (NCT01568099) and its extension studies, sponsored by Affiris, in 21 people with early-stage Parkinson’s supported the vaccine’s safety and tolerability with repeat injections (six doses in total). Patients treated at the highest dose, 75 micrograms, also showed a 51% drop in levels of alpha-synuclein aggregates in the cerebrospinal fluid that surrounds the brain and spinal cord, its researchers reported in 2020, supporting further clinical testing.
The planned Phase 2 trial of ACI-7104 will evaluate an “improved” version of the vaccine, Streffer said. It is to be an adaptive and biomarker-based study that will initially determine an optimally safe and effective dose and confirm the Phase 1 trial’s findings. Up to 150 additional Parkinson’s patients will then be enrolled for treatment and assessment at the selected dose.
“This study is in preparation,” Streffer said. “We are planning to include the first participants later this year.”
AC Immune also has two candidate vaccines for Alzheimer’s disease, ACI-35.030 and ACI-24.060, in clinical testing.
“We believe these programs, together with our cutting-edge diagnostic imaging agents, position AC Immune to lead the field towards the earlier diagnosis and prevention of neurodegenerative disease,” said Andrea Pfeifer, CEO of AC Immune.