SDF-1 mRNA gene therapy for restoration of erectile function
用于恢复勃起功能的 SDF-1 mRNA 基因治疗
基本信息
- 批准号:10325466
- 负责人:
- 金额:$ 31.49万
- 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:2021-09-15 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdipose tissueAdrenergic alpha-AntagonistsAffectAmericanAnxietyApoptoticBindingBiologicalBlood PlateletsBlood VesselsBrainCOVID-19 vaccineCXCR4 ReceptorsCardiovascular AgentsChronic DiseaseCialisClinicClinical ResearchCodeDataDevicesDiabetes MellitusDiseaseDoseDrug InteractionsDrug KineticsDyslipidemiasEconomic BurdenEngineeringErectile dysfunctionFibrosisGangliaGene ExpressionGenesGrowth FactorHeartHeart DiseasesHypertensionIn VitroIndividualInjection of therapeutic agentInjectionsInjuryInsuranceInvestigational DrugsInvestigational New Drug ApplicationMaintenanceMalignant NeoplasmsMental DepressionMessenger RNAModalityModelingMuscleNerveNerve TissueNeuronsNitratesNucleic AcidsOralPathway interactionsPatientsPelvisPenile ProsthesisPerformancePersonal SatisfactionPharmaceutical PreparationsPharmacologyPhasePhase I Clinical TrialsPlasmaPoriferaPreclinical TestingProceduresProstate Cancer therapyProteinsPublic HealthQuality of lifeRandomized Controlled TrialsRattusSafetySeriesSignal TransductionSiteSmall Business Innovation Research GrantStandardizationStromal Cell-Derived Factor 1SymptomsTechnologyTissuesToxicologyTranslatingTreatment ProtocolsUrinary IncontinenceVacuumVasodilator AgentsViagraWorkangiogenesisbasechemokineclinical infrastructurecytotoxicitydesigndosagedrug distributionefficacy studygene therapyhealingimprovedin vivoinhibitor/antagonistinjuredmenminimally invasivenerve injuryneurogenesisnovelpenisphosphoric diester hydrolaseregenerativeregenerative therapyrepairedrestorationsafety studyside effectstem cell migrationstem cellsuptakevardenafil
项目摘要
Abstract
Erectile dysfunction (ED) affects about 18 million men in the U.S. and is estimated to affect 322 million men
worldwide by 2025. ED can have a profound negative impact on quality of life and well-being and is often
associated with anxiety and depression. ED also represents a significant economic burden, with over $4 billion
spent in 2017 in the U.S. ED is a common consequence of diseases that affect the microvasculature and nervous
tissue, including common chronic diseases such as hypertension, dyslipidemia, and diabetes, and a frequent
side effect of prostate cancer treatment. Currently available ED treatments are moderately effective at best, have
high discontinuation rates, and address only the symptoms, not the underlying causes. To address the need
for novel treatments for ED, Evincis Bio is developing a regenerative gene therapy based on stromal
cell‐derived factor‐1 (SDF-1) mRNA. SDF-1 is a highly conserved chemokine that regulates an endogenous
repair pathway used by many tissues throughout the body, such as the heart, brain, muscle, and vasculature.
Often upregulated following injury, SDF-1 signaling leads to stem cell migration to the injury site. SDF-1 binds to
its receptor CXCR4 on resident tissues, including nerves, muscle, and vasculature, inducing angiogenesis,
neurogenesis, anti-apoptotic pathways, and upregulating the expression of growth factors. Evincis has
demonstrated that SDF-1 penile injections improve erectile function in a rat model of ED. This
improvement was associated with increased major pelvic ganglion (MPG) neurons, decreased penile fibrosis,
and increased growth factor expression in penile tissues. SDF-1 penile injections were shown to upregulate the
expression of stem cell-associated genes in the MPG and erectile tissue. Evincis has also demonstrated the
feasibility of targeted mRNA-based gene expression in penile tissues. In fact, mRNA technology is being
utilized by several current COVID-19 vaccines. In this Phase I project, Evincis will conduct in vitro and in vivo
dosing, efficacy, and safety studies to support further clinical research. This will be accomplished through the
following specific aims: 1) Screen engineered mRNA candidates in vitro for expression efficiency and cytotoxicity;
2) Determine EVI-200 dosage, expression duration, and safety in vivo; and 3) Perform efficacy and cancer safety
studies in vivo. These studies will support further Phase II work, in which Evincis will expand the preclinical
testing to additional disease states, investigate different nucleic acid carriers, perform pharmacokinetic and
toxicology studies, and initiate the GMP setup necessary to support an IND application and start a Phase I clinical
trial. Evincis will pursue approval as a biologic, resulting in a product J-code and stand-alone reimbursement for
the in-office procedure. If successful, EVI-200 will be the first therapy specifically designed to treat the
underlying causes of ED due to injury of nerve, muscle, and vascular tissue, and potentially provide a
cure for millions of individuals. This project will also serve as a proof-of-concept for EVI-200 as an mRNA-
based regenerative therapy for other conditions, such as urinary incontinence.
摘要
勃起功能障碍(艾德)影响美国约1800万男性,估计影响3.22亿男性
到2025年全球艾德可对生活质量和健康产生深远的负面影响,
与焦虑和抑郁有关。艾德也是一个巨大的经济负担,
艾德是影响微血管和神经系统疾病的常见后果。
组织,包括常见的慢性疾病,如高血压,血脂异常和糖尿病,以及常见的
前列腺癌治疗副作用目前可用的艾德治疗充其量是中等有效的,
高停药率,并且只解决症状,而不是根本原因。为了满足
对于艾德的新疗法,Evincis Bio正在开发一种基于基质的再生基因疗法。
细胞衍生因子-1(SDF-1)mRNA。SDF-1是一种高度保守的趋化因子,调节内源性
修复途径,用于全身许多组织,如心脏、大脑、肌肉和脉管系统。
通常在损伤后上调,SDF-1信号传导导致干细胞迁移到损伤部位。SDF-1与
其受体CXCR 4在包括神经、肌肉和脉管系统的驻留组织上,诱导血管生成,
神经发生、抗凋亡途径和上调生长因子的表达。Evincis已经
证明SDF-1阴茎注射改善ED大鼠模型的勃起功能。
改善与主要盆神经节(MPG)神经元增加,阴茎纤维化减少,
并增加阴茎组织中生长因子的表达。SDF-1阴茎注射显示上调了
MPG和勃起组织中干细胞相关基因的表达。Evincis还展示了
阴茎组织中靶向mRNA基因表达的可行性。事实上,mRNA技术
目前的几种COVID-19疫苗都利用了这一点。在这个I期项目中,Evincis将在体外和体内进行
剂量、疗效和安全性研究,以支持进一步的临床研究。这将通过以下方式实现:
具体目的如下:1)体外筛选工程化mRNA候选物的表达效率和细胞毒性;
2)确定EVI-200剂量、表达持续时间和体内安全性;以及3)进行功效和癌症安全性研究。
体内研究。这些研究将支持进一步的II期工作,其中Evincis将扩大临床前研究。
检测其他疾病状态,研究不同的核酸携带者,进行药代动力学和
毒理学研究,并启动支持IND申请所需的GMP设置,并开始I期临床试验
审判Evincis将寻求作为生物制剂的批准,从而获得产品J代码和独立报销,
办公室内的程序。如果成功,EVI-200将是第一个专门设计用于治疗
由于神经、肌肉和血管组织损伤而导致艾德的根本原因,并可能提供一种治疗方法
治愈数百万人。该项目还将作为EVI-200作为mRNA的概念验证-
基于再生治疗的其他条件,如尿失禁。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Nikolai Anton Sopko其他文献
Nikolai Anton Sopko的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
相似海外基金
Deciphering the role of adipose tissue in common metabolic disease via adipose tissue proteomics
通过脂肪组织蛋白质组学解读脂肪组织在常见代谢疾病中的作用
- 批准号:
MR/Y013891/1 - 财政年份:2024
- 资助金额:
$ 31.49万 - 项目类别:
Research Grant
ESTABLISHING THE ROLE OF ADIPOSE TISSUE INFLAMMATION IN THE REGULATION OF MUSCLE MASS IN OLDER PEOPLE
确定脂肪组织炎症在老年人肌肉质量调节中的作用
- 批准号:
BB/Y006542/1 - 财政年份:2024
- 资助金额:
$ 31.49万 - 项目类别:
Research Grant
Canadian Alliance of Healthy Hearts and Minds: Dissecting the Pathways Linking Ectopic Adipose Tissue to Cognitive Dysfunction
加拿大健康心灵联盟:剖析异位脂肪组织与认知功能障碍之间的联系途径
- 批准号:
479570 - 财政年份:2023
- 资助金额:
$ 31.49万 - 项目类别:
Operating Grants
Determinants of Longitudinal Progression of Adipose Tissue Inflammation in Individuals at High-Risk for Type 2 Diabetes: Novel Insights from Metabolomic Profiling
2 型糖尿病高危个体脂肪组织炎症纵向进展的决定因素:代谢组学分析的新见解
- 批准号:
488898 - 财政年份:2023
- 资助金额:
$ 31.49万 - 项目类别:
Operating Grants
Activation of human brown adipose tissue using food ingredients that enhance the bioavailability of nitric oxide
使用增强一氧化氮生物利用度的食品成分激活人体棕色脂肪组织
- 批准号:
23H03323 - 财政年份:2023
- 资助金额:
$ 31.49万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Development of new lung regeneration therapies by elucidating the lung regeneration mechanism of adipose tissue-derived stem cells
通过阐明脂肪组织干细胞的肺再生机制开发新的肺再生疗法
- 批准号:
23K08293 - 财政年份:2023
- 资助金额:
$ 31.49万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
A study on the role of brown adipose tissue in the development and maintenance of skeletal muscles
棕色脂肪组织在骨骼肌发育和维持中作用的研究
- 批准号:
23K19922 - 财政年份:2023
- 资助金额:
$ 31.49万 - 项目类别:
Grant-in-Aid for Research Activity Start-up
Adipose Tissue T Cell Polarization and Metabolic Health in Persons Living with HIV
HIV 感染者的脂肪组织 T 细胞极化和代谢健康
- 批准号:
10619176 - 财政年份:2023
- 资助金额:
$ 31.49万 - 项目类别:
Estrogen Signaling in the Ventromedial Hypothalamus Modulates Adipose Tissue Metabolic Adaptation
下丘脑腹内侧区的雌激素信号调节脂肪组织代谢适应
- 批准号:
10604611 - 财政年份:2023
- 资助金额:
$ 31.49万 - 项目类别:
Obesity and Childhood Asthma: The Role of Adipose Tissue
肥胖和儿童哮喘:脂肪组织的作用
- 批准号:
10813753 - 财政年份:2023
- 资助金额:
$ 31.49万 - 项目类别:














{{item.name}}会员




