# Novel Extended Release Glaucoma Therapy for Once Daily Dosing

> **NIH NIH R24** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2020 · $1,137,678

## Abstract

Glaucoma is the leading cause of irreversible blindness in the world. Elevated intraocular pressure (IOP) is the
most significant risk factor contributing to death of retinal ganglion cells (RGCs) and resulting visual field loss in
primary open angle glaucoma (POAG). The current standard of care for glaucoma includes treatment with IOP-
lowering medications delivered topically as eye drops. However, many patients continue to lose visual fields
despite being on IOP-lowering drops. We have taken a comprehensive genetics approach to seek new drug
targets that may address the limitations of current therapies. We have demonstrated that Cacna2d1 is
specifically linked to high IOP both in mice and humans. We have also shown that a selective Cacna2d1
blocker exhibits potent IOP-lowering activity that can achieve a maximal IOP reduction >40% that does not
return to baseline for ~33 hours when delivered by bioadhesive microemulsion. We have also determined that
CACNA2D1 is localized to the CB, TM and RGCs, suggesting that inhibitors of this protein could both lower
IOP and protect RGCs. Lastly, we have shown that the degree of IOP lowering is correlated with the gene
haplotype, thus demonstrating the potential of tailoring treatment to a patient’s genetic profile. Our overall
objective is to develop and validate one or more novel topical formulations to deliver the effective drugs to
inhibit CACNA2D1 in a once daily topical formulation. This treatment strategy will reduce the burden to the
patient, increase compliance and lead to better visual outcomes. Our central hypothesis is that a small
molecule that targets CACNA2D1—when formulated in a topical microemulsion—will elicit an IOP-lowering
response that is greater in amplitude and duration than other glaucoma medications. Overall strengths of this
proposal include: 1) the combination of a strong interdisciplinary team; 2) the successful utilization of a
genetics approach to identify a new drug target for blocking glaucoma-related increases in IOP and RGC
death; 3) the potential for utilizing our novel drug for precision medicine and; 4) the development and
optimization of an innovative IOP delivery strategy using an extended-release formulation. In this proposal, we
provide proof-of-concept data and address key feasibility questions by establishing efficacy,
pharmacodynamics, biocompatibility and biodistribution of our novel microemulsion treatment. We develop a
novel topical once daily microemulsion formulation as a new glaucoma therapy; measure the movement of
CACNA2D1 inhibitors across the cornea, determine pharmacokinetic movements in the eye and assess full-
body biodistribution; establish the mechanism of action of CACNA2D1 inhibitors as glaucoma therapies;
determine if the haplotype of Cacna2d1 influences the IOP-lowering response to our formulation(s); and
prepare and submit an IND application to the FDA. These results will position us to proceed directly to a Phase
II demonstration project in pr...

## Key facts

- **NIH application ID:** 9912475
- **Project number:** 1R24EY029950-01A1
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** MONICA M JABLONSKI
- **Activity code:** R24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,137,678
- **Award type:** 1
- **Project period:** 2020-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9912475

## Citation

> US National Institutes of Health, RePORTER application 9912475, Novel Extended Release Glaucoma Therapy for Once Daily Dosing (1R24EY029950-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9912475. Licensed CC0.

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