Clene Presents Preclinical Data Supporting CNM-Au8 for Parkinson's Disease
Breakthrough Clinical Results
Clene Inc. announced positive preclinical data for CNM-Au8 in treating Parkinson's disease (PD). A novel neuronal model demonstrated CNM-Au8's ability to improve mitochondrial health, reduce inflammation, restore cellular metabolism, and normalize gene expression in both familial and sporadic PD. These findings, presented at the Michael J. Fox Foundation H2 Therapeutics Stewardship Meeting, build upon Phase 2 data showing CNM-Au8's positive effects on brain energy metabolites in PD patients. The company plans to explore a Phase 2 clinical trial for CNM-Au8 in PD, alongside ongoing late-stage clinical studies for ALS and a planned Phase 3 trial for MS.
Key Highlights
- CNM-Au8 improved mitochondrial health and reduced ROS in familial and sporadic Parkinson's disease neuronal models.
- CNM-Au8 reduced inflammation by lowering senescence-related inflammatory proteins in sporadic PD neurons.
- CNM-Au8 restored cellular metabolism and normalized dysregulated gene expression in both familial and sporadic PD models.
- CNM-Au8 showed a favorable safety profile in the preclinical study.
Incidence and Prevalence
Latest Global Estimates of Parkinson's Disease Incidence and Prevalence
Global Projections and General Prevalence
The prevalence of Parkinson's disease (PD) is projected to double by 2030, highlighting the growing public health concern. Currently, PD affects 1% of the population over 60 years old. With global increases in the aging population, Parkinson's disease presents huge economic and societal burdens.
Young-Onset Parkinson's Disease (YOPD)
A 2024 systematic review and meta-analysis revealed that the age-standardized incidence of Young-onset Parkinson's disease (YOPD) was 1.3 per 100,000 person-years population worldwide. In European populations specifically, the age-standardized incidence of YOPD was 1.2 per 100,000 person-years. YOPD refers to Parkinson's disease in individuals younger than 40 years.
This comprehensive analysis searched literature in PubMed, Scopus, and Web of Science in May 2022, including retrospective, prospective, and cross-sectional observational population-based studies that reported the prevalence or incidence of PD in individuals younger than 40 years with known diagnostic criteria. The study noted that estimates of the incidence in low-income countries remain scarce.
Regional Studies
Spain
A 2021 study in Spain found a PD prevalence of 118.4 (95%CI: 117.3-119.6) per 100,000 population. The same study reported a PD incidence of 9.4 (95%CI: 5.42-13.4) per 100,000 population.
Germany
A 2021 German study estimated age- and sex-specific incidence of PD, finding that men had higher incidences of PD than women at all ages. The highest incidences for both groups were estimated for the age of 85 years with an incidence of 538.49 per 100,000 person-years (py) in men and 284.09 per 100,000 py in women.
Research Implications
Researchers have emphasized that healthcare providers and policymakers should be aware that much more effective tools are required to improve monitoring and certain diagnoses of YOPD. This highlights the need for continued research and development of diagnostic and monitoring tools for Parkinson's disease across all age groups.
Emerging Mechanism of Action
Emerging Mechanisms of Action for Parkinson's Disease
Neuroimaging and Structural Biomarkers
Recent research identifies temporal lobe atrophy as a critical biomarker for cognitive decline in Parkinson's disease (PD). Patients developing PD-MCI show significant right temporal atrophy at baseline and extensive temporal lobe atrophy at follow-up. Progressive bilateral frontal lobe atrophy is observed in patients converting to PD-MCI, with baseline right temporal atrophy correlating with striatal dopaminergic degeneration.
Dopaminergic Mechanisms
Dopaminergic medication improves dual task walking in PD patients by facilitating the recruitment of the left prefrontal cortex during these tasks. Dopamine transporter (DAT) SPECT specific binding ratio has emerged as the most impactful predictor for time to initiation of symptomatic therapy.
Digital Biomarkers and Assessment Tools
Computer vision technology (DeepLabCut) now quantifies bradykinesia from smartphone videos of finger tapping as a contactless method correlating well with clinical ratings. Quantitative digitography (QDG) during repetitive alternating finger tapping provides reliable metrics for cardinal motor signs in PD and can track disease progression over years.
Oculomotor Function
Eye movement abnormalities are increasingly recognized as early biomarkers of PD. Patients exhibit distinct saccadic abnormalities including hypometric saccades and increased anti-saccade errors, which correlate with executive dysfunction. AI-driven eye-tracking models show promise for automated PD diagnosis and progression tracking.
Molecular Mechanisms
Recent research focuses on targeting oxidative stress and neuroinflammation as key early events in PD pathology. Compounds like Astragaloside IV protect dopaminergic neurons by activating Nrf2 pathways and suppressing NFκB/NLRP3 inflammasome signaling. Xanthotoxin demonstrates neuroprotective effects by reducing oxidative stress and attenuating MAPK kinases activation.
α-Synuclein Targeting
α-synuclein (α-syn) aggregation inhibition is an active research area, as toxic α-syn species cause oxidative stress, membrane penetration, and synaptic and mitochondrial dysfunction.
Microglial Polarization
Inhibiting M1 while boosting M2 microglial activation represents a potential treatment approach. Apilarnil reduces M1 microglial activity while enhancing M2 microglial activity through modulation of specific markers.
Signaling Pathways
The Wnt/β-catenin signaling pathway dysregulation is implicated in PD progression. Natriuretic peptides affect this pathway through a Frizzled receptor-mediated mechanism, protecting against neurotoxin insult. PPARδ signaling activation shows neuroprotective potential, with agonists improving locomotor activity and expressions of PD-related genes. The Nrf2-Keap1-ARE and SIRT1 signaling pathways play major roles in PD pathogenesis, with compounds like betanin showing neuroprotective effects through their upregulation.
Mitophagy and Mitochondrial Function
Idebenone, a mitochondria-targeting therapeutic drug, reduces dopaminergic neuron damage by upregulating mitochondrial autophagy-related proteins and activating the Parkin/PINK1 mitochondrial autophagy pathway.
Drug used in other indications
CNM-Au8 Clinical Trials Beyond Parkinson's Disease
Based on the information available, I cannot provide specific details about other indications for which CNM-Au8 is being trialed beyond Parkinson's disease, nor can I describe the intervention models used in these trials.
The context does not contain information about: - Additional disease indications for CNM-Au8 clinical trials - Intervention protocols used in these trials - Dosing regimens for CNM-Au8 - Administration methods for neurodegenerative conditions - Trial designs or models being implemented
For comprehensive information about CNM-Au8 clinical trials, including other indications beyond Parkinson's disease and their specific intervention models, it would be necessary to consult clinical trial registries, published research literature, or official communications from Clene Nanomedicine, the developer of this gold nanocrystal suspension.
