Next-generation PET tracer detects pathological alpha-synuclein with improved signal-to-noise ratio
Oral presentation at AAIC further demonstrates the strength of AC Immune’s Morphomer™ platform for generating highly selective small molecule diagnostics
The compelling preclinical results demonstrate enhanced contrast and alpha-synuclein target specificity, putting AC Immune’s PET tracer in a strong position to become a first-in-class precision diagnostic tool for Parkinson’s disease (PD). No effective diagnostic agents exist today for PD and other alpha-synucleinopathies, such as multiple system atrophy (MSA), and Lewy Body Dementia (LBD), representing substantial unmet clinical need.
Alpha-synuclein misfolding, aggregation and seeding are the molecular basis for the formation of Lewy bodies, a hallmark of PD, MSA, and LBD. The availability of non-invasive diagnostic tools that can distinguish alpha-synucleinopathies from other proteinopathies or normal physiological situations would enable – for the first time – accurate clinical diagnosis, monitoring of disease progression and benefits of drug interventions. ACI-12589 demonstrates significantly increased target occupancy compared to previous-generation candidates as well as a significantly improved signal specificity.
AC Immune’s PET tracers are derived from the Company’s innovative Morphomer™ discovery platform, which accelerates the design, development and synthesis of conformation-specific small molecules to power successful diagnostic and therapeutic approaches. The Morphomer™ platform has produced multiple small molecules with clinical proof-of-concept that bind selectively to pathological forms of human proteins such as alpha-synuclein and Tau.
Based on proof-of-concept data presented at this year’s AAT-AD/PD™ conference,
Dr. Capotosti’s presentation was titled Developing a novel alpha-synuclein positron emission tomography (PET) tracer for the diagnosis of a-synucleinopathies. Key highlights from the presentation include:
- ACI-3847, a first-generation alpha-synuclein-PET tracer, showed good brain uptake and very low non-specific retention in a first-in-human study in idiopathic PD patients and healthy volunteers
- The data on ACI-3847 suggested to test the PET tracer in alpha-synuclein-pathologies with higher levels of alpha-synuclein accumulation
- AC Immune’s Morphomer™ platform also led to the discovery of ACI-12589 with excellent target occupancy and signal specificity ex vivo and an expected optimal signal-to-noise ratio in patients
- Data presented will show ACI-12589 as a potential first- and best-in-class imaging agent for the diagnosis of PD
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Source: AC Immune SA