Purpose: Complement C1q, the initiating molecule of the classical complement cascade, is involved in synapse elimination and neuronal loss in neurodegenerative diseases including glaucoma. Here we report an evaluation of the safety, tolerability, and ocular pharmacokinetics (PK) and pharmacodynamics of intravitreal (IVT) injections of ANX007, an anti-C1q monoclonal antibody fragment that blocks activation of the classical complement cascade.
Design: An open-label, single-dose-escalation phase Ia study followed by a double-masked, randomized, sham-controlled, repeat-injection phase Ib study.
Participants: A total of 26 patients with primary open-angle glaucoma.
Methods: Nine patients with primary open-angle glaucoma (mean Humphrey visual field deviation between -3 and -18 decibels [dB]) were enrolled in phase Ia and received single doses of ANX007 (1.0 mg, n = 3; 2.5 mg, n = 3; or 5.0 mg, n = 3). Seventeen patients (mean Humphrey visual field deviation between -3 and -24 dB) were enrolled in phase Ib and randomized to 2 monthly doses of ANX007 (sham, n = 6; 2.5 mg ANX007, n = 6; or 5 mg ANX007, n = 5).
Main Outcome Measures: Safety and tolerability (including laboratory evaluation of urinalysis, complete blood count, and serum chemistries), ANX007 PK, target engagement, and immunogenicity.
Results: The mean age overall was 70 years in phase Ia and 68 years in phase Ib. In both studies, no serious adverse events were observed, no non-ocular treatment-emergent adverse events (TEAEs) attributable to study drug were reported, and ocular TEAEs were mild. Intraocular pressure returned to normal levels for all patients within 45 minutes of IVT injection. No clinically significant deviations in laboratory results were observed. In the phase Ib study, C1q in the aqueous humor was reduced to undetectable levels in both the 2.5 mg and 5 mg cohorts 4 weeks after the first ANX007 dose.
Conclusions: In these studies, single and repeat IVT ANX007 injections were well tolerated and demonstrated full target engagement 4 weeks after dosing with both low and high doses, supporting monthly or less-frequent dosing. Further investigation in neurodegenerative ocular diseases is warranted.
Financial Disclosures: Proprietary or commercial disclosure may be found after the references.
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http://dx.doi.org/10.1016/j.xops.2023.100290 | DOI Listing |
J Clin Invest
January 2025
Center for Inherited Myology Research, Virginia Commonwealth University, Richmond, United States of America.
Background: Myotonic dystrophy type 1 (DM1) is a multisystemic, CTG repeat expansion disorder characterized by a slow, progressive decline in skeletal muscle function. A biomarker correlating RNA mis-splicing, the core pathogenic disease mechanism, and muscle performance is crucial for assessing response to disease-modifying interventions. We evaluated the Myotonic Dystrophy Splice Index (SI), a composite RNA splicing biomarker incorporating 22 disease-specific events, as a potential biomarker of DM1 muscle weakness.
View Article and Find Full Text PDFArch Womens Ment Health
January 2025
Department of Psychology, University of Wisconsin-Madison, 1202 W. Johnson St, Madison, WI, 53706, USA.
Purpose: Given the lack of available and effective interventions to address the detrimental consequences of perinatal exposure to intimate partner violence (IPV) on maternal mental health, and reported very low access to IPV-related mental health services in Mexico, we examined the feasibility and efficacy of a culturally adapted, virtual, brief group psychosocial intervention designed to improve maternal mental and physical health and reduce IPV revictimization for pregnant women exposed to IPV. In this pilot randomized controlled trial, we evaluated maternal outcomes after participation in the Pregnant Moms' Empowerment Program (PMEP) in Mexico.
Methods: Women were recruited from social service agencies and health centers in the community, as well as social media advertisements that targeted pregnant women living in Mexico.
J Viral Hepat
February 2025
Monash Addiction Research Centre, Eastern Health Clinical School, Monash University, Melbourne, Victoria, Australia.
The World Health Organisation (WHO) has set goals to eliminate hepatitis C (HCV) as a global health threat by 2030. To meet this goal, Australia must increase testing and diagnosis, including expanding access to care through community pharmacists. This study aims to explore community pharmacists' preparedness to discuss and offer HCV testing and treatment.
View Article and Find Full Text PDFElife
January 2025
Department of Anatomy and Neurobiology, Boston University Chobanian & Avedisian School of Medicine, Boston, United States.
The basal ganglia (BG) are an evolutionarily conserved and phylogenetically old set of sub-cortical nuclei that guide action selection, evaluation, and reinforcement. The entopeduncular nucleus (EP) is a major BG output nucleus that contains a population of GABA/glutamate cotransmitting neurons (EP) that specifically target the lateral habenula (LHb) and whose function in behavior remains mysterious. Here, we use a probabilistic switching task that requires an animal to maintain flexible relationships between action selection and evaluation to examine when and how GABA/glutamate cotransmitting neurons contribute to behavior.
View Article and Find Full Text PDFAust Occup Ther J
February 2025
Department of Health Sciences, Mental Health, Activity and Participation (MAP), Lund University, Lund, Sweden.
Introduction: Mental health service users often have sensory processing difficulties hampering their ability to cope with mental health problems and occupational engagement. However, there is little knowledge of sensory processing and its relation to these factors. Hence, this current study aims to investigate sensory processing patterns in relation to coping and occupational engagement for the target group.
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