[18F]ACI-15916 is a novel PET radiotracer developed by AC Immune for imaging alpha-synuclein pathology in vivo. This early Phase 1 study aims to evaluate the safety, biodistribution, and brain uptake of the tracer in patients with alpha-synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA).
| Field | Value |
|---|---|
| Trial ID | NCT06891703 |
| Phase | Early Phase 1 |
| Status | Recruiting |
| Agent | [18F]ACI-15916 |
| Target | Alpha-synuclein aggregates |
| Imaging Modality | PET |
| Sponsor | AC Immune SA |
Alpha-synucleinopathies represent a group of neurodegenerative disorders characterized by intracellular aggregation of the protein alpha-synuclein into insoluble fibrils.
| Disease | Clinical Features | Primary Pathology |
|---|---|---|
| Parkinson's Disease | Resting tremor, bradykinesia, rigidity | Lewy bodies in substantia nigra |
| Dementia with Lewy Bodies | Fluctuating cognition, visual hallucinations | Cortical Lewy bodies |
| Multiple System Atrophy | Autonomic failure, cerebellar ataxia | Glial cytoplasmic inclusions |
| Pure Autonomic Failure | Orthostatic hypotension | Lewy bodies in autonomic nerves |
Alpha-synuclein is a 140-amino acid protein encoded by the SNCA gene:
Alpha-synuclein (α-syn) is a 140-amino acid protein that forms Lewy bodies and Lewy neurites in Parkinson's disease and related disorders. The [18F]ACI-15916 tracer is designed to bind selectively to pathological alpha-synuclein aggregates, enabling in vivo visualization of neurodegeneration.
Current alpha-synuclein imaging challenges:
[18F]ACI-15916 aims to address this gap by providing a non-invasive method to detect alpha-synuclein deposition in the living brain.
[18F]ACI-15916 is a small molecule radioligand:
| Mechanism | Description | Neuronal Effect |
|---|---|---|
| Mitochondrial dysfunction | Complex I inhibition | Energy depletion |
| ER stress | Unfolded protein response | Apoptosis |
| Oxidative stress | ROS generation | Membrane damage |
| Neuroinflammation | Microglial activation | Accelerated death |
| Synaptic dysfunction | Vesicle release impairment | Connectivity loss |
| Axonal transport defects | Tau phosphorylation | Degeneration |
The progression of Lewy body pathology follows a predictable pattern:
| Stage | Affected Regions | Clinical Correlation |
|---|---|---|
| 1 | Dorsal motor nucleus, olfactory bulb | Pre-motor symptoms |
| 2 | Substantia nigra, locus coeruleus | Motor symptoms emerge |
| 3 | Mesocortex, basal forebrain | Cognitive changes |
| 4 | Temporal cortex, limbic system | Dementia onset |
| 5 | Neocortex | Advanced dementia |
| 6 | Primary sensory cortex | Severe impairment |
Primary Objectives:
Secondary Objectives:
| Group | Purpose |
|---|---|
| Parkinson's disease patients | Target pathology presence |
| Dementia with Lewy bodies patients | Cortical involvement |
| Multiple system atrophy patients | Different α-syn aggregate type |
| Healthy controls | Baseline for comparison |
Safety Endpoints:
Pharmacokinetic Endpoints:
In vivo alpha-synuclein imaging could:
Confirm clinical diagnosis:
Disease staging:
Treatment monitoring:
Alpha-synuclein PET enables:
| Tracer | Target | Development Stage | Company |
|---|---|---|---|
| [18F]ACI-15916 | α-syn aggregates | Phase 1 | AC Immune |
| [11C]PiB | Amyloid-β | Approved | Avid/GE |
| [18F]Flortaucipir | Tau | Phase 3 | Avid/GE |
| [18F]RO948 | Tau | Phase 2 | Roche |