Developing a multivalent agent for long-lasting treatment of diabetic macular edema
开发用于长期治疗糖尿病黄斑水肿的多价药物
基本信息
- 批准号:10324534
- 负责人:
- 金额:$ 22.47万
- 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 2023-08-31
- 项目状态:已结题
- 来源:
- 关键词:AdoptedAffectAffinityAgeAngiopoietin-2Animal ModelAptitudeBindingBiologicalBiomedical EngineeringBlindnessChronicClinicalClinical TrialsCombined Modality TherapyComplementComputer ModelsDisease ManagementDoseEquilibriumExudative age-related macular degenerationFundingHalf-LifeHealth Care VisitHumanHyaluronic AcidIn VitroInjectionsLinkMaximum Tolerated DoseMeasuresMetabolic Clearance RateMethodsModelingMolecular Sieve ChromatographyMusNucleic AcidsOryctolagus cuniculusOutcomePathway interactionsPatientsPerformancePharmaceutical PreparationsPhasePhase I Clinical TrialsPolymersPublishingRadialRegimenReportingRestSafetyScheduleSmall Business Innovation Research GrantSolubilityTestingTherapeuticTimeTime ManagementToxic effectTranslatingVascular Endothelial Growth FactorsWorkaging populationaptamerarmbevacizumabcomorbiditydesigndiabetes managementdiabeticdosagedrug efficacyefficacy testingexperiencefollow-upimprovedindexingintravitreal injectionlight scatteringmacular edemameetingsnext generationnovelnovel strategiesparticlephase III trialpre-clinical researchprogramsprototyperanibizumabstandard of caresystemic toxicity
项目摘要
PROJECT ABSTRACT
DME is the leading cause of blindness in the working age population. The anti-VEGF agents are currently the standard of
care for DME, but these treatments are far from optimal: patients need to receive 8-12 intravitreal injections in the first
year and continue regular follow-up and treatment for the rest of their lives. These patients also have to spend significant
time managing diabetes and other comorbidities – a recent study reported that an average DME patient has ~30 healthcare
visit days a year. It is therefore extremely difficult for them to balance work and disease management. Consequently, the
real-world outcomes of DME patients are significantly worse than the results from controlled trials due to under-treatment
and loss to follow-up. Longer-lasting therapeutics are urgently needed.
The duration of drug efficacy is determined by 3 key factors: drug potency, which affects the minimum effective
concentration (MEC); drug half-life (t1/2), which determines how fast it is metabolized; initial drug dosage, which
determines how long it can last until it reaches MEC. The benefits of improving these factors are validated: 1) Aflibercept
leveraged bivalency to achieve higher potency than Ranibizumab and enabled a longer duration (bimonthly vs. monthly);
2) extensive studies have shown that increasing the hydrodynamic radius (RH) of a drug proportionally elongates its
vitreous half-life, and multiple programs are being developed to leverage this principle; 3) Brolucizumab adopted a much
higher dose than the approved anti-VEGF agents and reported a longer duration in the recent phase 3 trials in wet AMD.
While these programs proved the feasibility to improve drug duration through rational bioengineering, they each tackles
one factor and only achieved incremental improvement (~3-month duration). Simultaneously improving all 3 factors may
unlock dramatic improvement but is extremely challenging.
The purpose of this SBIR is to develop a novel multivalent polymer conjugate of therapeutic aptamers that simultaneously
improve all 3 factors of drug duration for the first time, enabling significantly longer-lasting treatment for DME. To that
end, the Aptitude team has accumulated extensive experience in aptamer discovery. We have previously developed the
Particle Display method that significantly improves the aptamer performance. We have also performed significant
preliminary studies to prove the feasibility of constructing multivalent polymer conjugates. Moreover, we have made
further improvement to directly screen for fully modified aptamers that possess superior stability and performance
compared to the previous aptamers. Our expertise in aptamer discovery is complemented by our collaborators' expertise
in DME preclinical research and clinical trials. If successful, this project has the potential of bringing more efficacious
and affordable treatment to DME patients.
项目摘要
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
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Qiang Gong其他文献
Qiang Gong的其他文献
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{{ truncateString('Qiang Gong', 18)}}的其他基金
Fully modified bispecific aptamer for effective combination therapy of neovascular ocular diseases
完全修饰的双特异性适体可有效联合治疗新生血管性眼病
- 批准号:
9909857 - 财政年份:2020
- 资助金额:
$ 22.47万 - 项目类别:
Targeting SDF-1 for effective wet AMD treatment
靶向 SDF-1 进行有效的湿性 AMD 治疗
- 批准号:
10224211 - 财政年份:2020
- 资助金额:
$ 22.47万 - 项目类别:
Fully modified bispecific aptamer for effective combination therapy of neovascular ocular diseases
完全修饰的双特异性适体可有效联合治疗新生血管性眼病
- 批准号:
10578645 - 财政年份:2020
- 资助金额:
$ 22.47万 - 项目类别:
Fully modified bispecific aptamer for effective combination therapy of neovascular ocular diseases
完全修饰的双特异性适体可有效联合治疗新生血管性眼病
- 批准号:
10622568 - 财政年份:2020
- 资助金额:
$ 22.47万 - 项目类别:
Targeting SDF-1 for effective wet AMD treatment
靶向 SDF-1 进行有效的湿性 AMD 治疗
- 批准号:
9408583 - 财政年份:2017
- 资助金额:
$ 22.47万 - 项目类别:
Particle display: a new paradigm in high throughput discovery of ultra-high perfo
粒子显示:超高通量高通量发现的新范例
- 批准号:
8838889 - 财政年份:2014
- 资助金额:
$ 22.47万 - 项目类别:
Particle display: a new paradigm in high throughput discovery of ultra-high perfo
粒子显示:超高通量高通量发现的新范例
- 批准号:
8976164 - 财政年份:2014
- 资助金额:
$ 22.47万 - 项目类别:
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