rhGDG-5

Glaucoma is a progressive, chronic condition that can have a significant impact on a patient’s health-related quality of life (HRQoL). Validated, disease-specific HRQoL tools such as the Health Utility for Glaucoma (HUG-5) tool and the Glaucoma Quality of Life Questionnaire (GlauQoL-17) can be used to monitor a patient’s quality of life. However, the utility of these tools in outpatient clinic practice is not well established. The primary objective of this study is to characterise the feasibility of administering periodic HRQoL questionnaires in glaucoma using a semi-automated workflow.

This study will be a single-centre, unblinded, randomised, parallel-group study with an exploratory data analysis framework. We aim to determine the feasibility of administering the HUG-5 in an outpatient clinic using a semi-automated workflow and determine patient engagement through email and telephone contact methods. We will also be investigating the association of the HUG-5 and GlauQoL-17 with patient visual field testing and visual acuity. Mean differences between groups will be tested with analysis of variance to determine if the frequency of calls affects burden, satisfaction and perceived value of information.

This study has been approved by the Hamilton Integrated Research Ethics board (ID: 13046) and will be conducted within Canadian Tri-Council Statement policy. Personal information of the study’s participants will be anonymised with identification codes and data will be kept on an encrypted server. Results of this study will be disseminated through peer-reviewed journals, conferences and internal meetings.

Heparin has been known to be a broad-spectrum inhibitor of viral infection for almost 70 years, and it has been used as a medication for almost 90 years due to its anticoagulant effect. This nontoxic biocompatible polymer efficiently binds to many types of viruses and prevents their attachment to cell membranes. However, the anticoagulant properties are limiting their use as an antiviral drug. Many heparin-like compounds have been developed throughout the years; however, the reversible nature of the virus inhibition mechanism has prevented their translation to the clinics. In vivo, such a mechanism requires the unrealistic maintenance of the concentration above the binding constant. Recently, we have shown that the addition of long hydrophobic linkers to heparin-like compounds renders the interaction irreversible while maintaining the low-toxicity and broad-spectrum activity. To date, such hydrophobic linkers have been used to create heparin-like gold nanoparticles and β-cyclodextrins. The former achieves a nanomolar inhibition concentration on a non-biodegradable scaffold. The latter, on a fully biodegradable scaffold, shows only a micromolar inhibition concentration. Here, we report that the addition of hydrophobic linkers to a new type of multifunctional scaffold (dendritic polyglycerol, dPG) creates biocompatible compounds endowed with nanomolar activity. Furthermore, we present an in-depth analysis of the molecular design rules needed to achieve irreversible virus inhibition. The most active compound (dPG-5) showed nanomolar activity against herpes simplex virus 2 (HSV-2) and respiratory syncytial virus (RSV), giving a proof-of-principle for broad-spectrum while keeping low-toxicity. In addition, we demonstrate that the virucidal activity leads to the release of viral DNA upon the interaction between the virus and our polyanionic dendritic polymers. We believe that this paper will be a stepping stone toward the design of a new class of irreversible nontoxic broad-spectrum antivirals.