PET Tracer ACI-12589 Captures Protein Clumps in Living Brain

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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A positron emission tomography (PET) tracer for the alpha-synuclein protein, whose damaging clumps mark Parkinson’s, captured its toxic aggregates in a living brain for a first time — instead of in post-mortem tissue as is done to date, scientists reported.

The tracer, called ACI-12589, is a diagnostic tool designed to identify people with specific diseases associated with the abnormal, toxic accumulation of aggregates of alpha-synuclein, collectively known as alpha-synucleinopathies.

These disorders, which include Parkinson’s, Lewy body dementia (LBD), and multiple system atrophy (MSA), are often difficult to from distinguish from one another, and from other disorders, based on symptoms alone.

“This is the first time that a PET tracer has reliably detected a-syn [alpha-synuclein] aggregates in patients’ brains … [representing] great clinical progress in the quest to provide a diagnostic tool for patients suffering from MSA and potentially other a-synucleinopathies,” Oskar Hansson MD, PhD, a neurology professor at Lund University, Sweden, said in a press release.

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“This could ultimately enable earlier and more reliable differentiation for this difficult-to-diagnose neurodegenerative disease,” he added. The tracer might also help in developing effective treatments by allowing researchers to see what impact they are having in patients.

Hansson presented the first live images of alpha-synuclein clumps in the human brain at the AD/PD 2022​ Conference that took place in Barcelona from March 15 to 20.

A senior consultant in neurology at Skåne University Hospital, Hansson was also the lead investigator of a proof-of-concept clinical trial in Sweden testing ACI-12589, developed by AC Immune. This work is supported by a grant from The Michael J. Fox Foundation (MJFF).

Positron emission tomography (PET) is an imaging technique that uses radioactive molecules, or probes, to visually detail tissues and organs, allowing researchers and doctors to observe metabolic processes inside the body.

ACI-12589 allows scientists to study the distribution of the toxic clumps of alpha-synuclein protein, and changes in their distribution as the disease progresses. Until now, the degree of alpha-synuclein and Lewy bodies in brain tissue could only be determined in tissue collected from patients after their death.

Data presented showed that ACI-12589 was able to identify and distinguish MSA patients from those with other alpha-synucleinopathies, such as Parkinson’s and LBD, and from healthy volunteers.

“The ACI-12589 patient brain scans indicate the signal specificity for a-syn in MSA patients versus healthy volunteers and patients with other a-synucleinopathies,” Hansson said.

According to AC Immune, ACI-12589 showed specificity for alpha-synuclein and an ability to detect the protein with enhanced contrast in brain areas affected by MSA, particularly cerebellar white matter.

“This first clinical validation for an a-syn [alpha-synuclein] PET tracer is a transformative step towards achieving our vision for developing precision medicines to treat neurodegenerative diseases,” said Andrea Pfeifer, CEO of AC Immune. “We look forward to continuing the collaboration to expand on these results in MSA and in other a-syn indications, such as Parkinson’s disease.”

ACI-12589 was developed using AC Immune’s proprietary Morphomer platform, which allows researchers to create small molecules, called morphomers, that specifically bind to and target misfolded proteins such as alpha-synuclein.

AC Immune will host a webinar on March 29 at 10 a.m. ET with Oskar Hansson to discuss trial findings, as well as the importance of biomarkers and precision medicine in diagnosing diseases like Parkinson’s and following their progression. AC Immune managers will also provide an overview of the company’s alpha-synuclein therapeutic and diagnostic work.

A question-and-answer session will follow the presentations. Those interested can attend the webinar by registering here.

“We are energized by the scientific possibilities presented by these findings. Selective imaging tracers can make an enormous difference in advancement of new therapies for synucleinopathies such as Parkinson’s disease,” said Jamie Eberling, PhD, senior vice president of research at MJFF.

“PET tracers for a primary pathological protein would be pivotal in transforming the future of Parkinson’s research and care,” he added.