Virally expressed Stanniocalcin-1 for long-term intraocular pressure reduction

病毒表达的 Stanniocalcin-1 用于长期降低眼压

基本信息

  • 批准号:
    10700892
  • 负责人:
  • 金额:
    $ 15.56万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-09-01 至 2026-08-31
  • 项目状态:
    未结题

项目摘要

ABSTRACT Glaucomatous optic neuropathy (GON) remains the world’s leading cause of irreversible blindness. At present time, the only reliable therapeutic target is the reduction of intraocular pressure (IOP), the most prevalent risk factor for GON, by means of pharmacologic, laser, or surgical intervention. Of these, pharmacologic therapy with topical eye drop monotherapy is generally the initial treatment of choice for patients with GON. Of the available medication classes, Prostaglandin F2 analogues (PGF2α) such as latanoprost are often used as first- line therapy. However, despite its success in reducing IOP in many patients, treatment non-response or side- effects limit its use in other patients. Furthermore, some studies estimate that less than half of patients use glaucoma eye drops as prescribed. Additionally, because of the pharmacokinetics and dosing regimens, fluctuation in IOP is common which also contributes to GON. We recently identified a peptide hormone, Stanniocalcin-1 (STC-1) that lowers IOP when applied topically and can be expressed in a sustained fashion with a viral vector to provide sustained IOP reduction. STC-1 was identified in our laboratory’s search of downstream effector molecules in latanoprost-mediated IOP reduction. To date, we have demonstrated that: 1) STC-1 is required for the IOP-lowering effects of latanoprost; 2) Topical STC-1 lowers IOP as a stand-alone drug and is equivalent to latanoprost for IOP reduction in normotensive mice; 3) IOP-lowering effects of STC-1 are independent of the FP receptor; 4) STC-1 lowers IOP in ocular hypertensive mice; 5) STC-1 lowers IOP in the domestic cat; and 6) STC-1 delivered by adeno-associated virus (AAV-STC-1) lowers IOP in a sustained fashion in normotensive mice. Our central hypothesis for this application is that expression of STC-1 with a viral vector will provide an effective, safe, and sustained treatment for IOP reduction that has potential to benefit the 80 million people worldwide afflicted by glaucoma. Aim 1 will confirm and optimize our preliminary data that STC-1 can be delivered with a viral vector to provide sustained IOP reduction in normotensive mice. The data will determine the optimal viral vector for IOP reduction and correlate with tissue expression, define minimal therapeutic dose of virus, and evaluate safety using histologic methods. Aim 2 will utilize the optimized viral construct and evaluate IOP reduction in models of ocular hypertension. A steroid- induced ocular hypertension model as well as the DBA/2J model of pigment dispersion will be used. Additional measures will include assessment of aqueous outflow parameters. Aim 3 will evaluate viral expression of STC-1 in domestic and primary congenital glaucoma cats as well as to evaluate aqueous humor outflow and safety. Combined with strong preliminary data and an expert mentorship panel, these aims will support our long- term goal of developing a novel, targeted, sustained delivery of an IOP-lowering agent for the estimated 80 million people worldwide with GON.
摘要

项目成果

期刊论文数量(8)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Transgene expression of Stanniocalcin-1 provides sustained intraocular pressure reduction by increasing outflow facility.
Stanniocalcin-1的转基因表达通过增加流出设施,可提供持续的眼内压降。
  • DOI:
    10.1371/journal.pone.0269261
  • 发表时间:
    2022
  • 期刊:
  • 影响因子:
    3.7
  • 作者:
  • 通讯作者:
Association of Metabolic Syndrome With Glaucoma and Ocular Hypertension in a Midwest United States Population.
  • DOI:
    10.1097/ijg.0000000000001968
  • 发表时间:
    2022-06-01
  • 期刊:
  • 影响因子:
    2
  • 作者:
  • 通讯作者:
Efficacy of Selective Laser Trabeculoplasty in Patients on Systemic Immunosuppressive Therapy.
选择性激光小梁成形术对接受全身免疫抑制治疗的患者的疗效。
  • DOI:
    10.1097/ijg.0000000000002259
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    2
  • 作者:
    Kaplan,TylerM;Hammer,JonD;Kohli,Darrel;Pacheco,JohannM;Hodge,DavidO;Khanna,CherylL;Sit,ArthurJ;Roddy,GavinW
  • 通讯作者:
    Roddy,GavinW
Multiple Systemic Vascular Risk Factors Are Associated With Low-Tension Glaucoma.
  • DOI:
    10.1097/ijg.0000000000001964
  • 发表时间:
    2022-01-01
  • 期刊:
  • 影响因子:
    2
  • 作者:
  • 通讯作者:
Effect of ATP-sensitive Potassium Channel Openers on Intraocular Pressure in Ocular Hypertensive Animal Models.
  • DOI:
    10.1167/iovs.63.2.15
  • 发表时间:
    2022-02-01
  • 期刊:
  • 影响因子:
    4.4
  • 作者:
    Roy Chowdhury U;Millar JC;Holman BH;Anderson KJ;Dosa PI;Roddy GW;Fautsch MP
  • 通讯作者:
    Fautsch MP
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Gavin W Roddy其他文献

Gavin W Roddy的其他文献

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{{ truncateString('Gavin W Roddy', 18)}}的其他基金

Virally expressed Stanniocalcin-1 for long-term intraocular pressure reduction
病毒表达的 Stanniocalcin-1 用于长期降低眼压
  • 批准号:
    10462675
  • 财政年份:
    2021
  • 资助金额:
    $ 15.56万
  • 项目类别:
Virally expressed Stanniocalcin-1 for long-term intraocular pressure reduction
病毒表达的 Stanniocalcin-1 用于长期降低眼压
  • 批准号:
    10297638
  • 财政年份:
    2021
  • 资助金额:
    $ 15.56万
  • 项目类别:

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