Vitiligo topical treatment applying a potent, highly selective MC1R agonist
使用强效、高选择性 MC1R 激动剂进行白癜风局部治疗
基本信息
- 批准号:10759768
- 负责人:
- 金额:$ 29.59万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-22 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdhesionsAdverse effectsAffectAgeAgonistAlopecia AreataAnguishAnti-Inflammatory AgentsAntioxidantsAnxietyAutoimmune ProcessAutoimmune ResponsesBindingBiological AssayCalcineurin inhibitorCaregiversCell surfaceCellular ImmunityCessation of lifeChildClinical TrialsComplexConsumptionCosmeticsCoupledCutaneousDNA DamageDNA RepairDangerousnessDataDepressed moodDiffusionDimethyl SulfoxideDiseaseEmotional StressEthnic OriginFontana-Masson stainFormulationFunctional disorderGeneral PopulationGenerationsGeneticGoalsHashimoto DiseaseHematoxylin and Eosin Staining MethodHistologyHomeostasisHumanHuman EngineeringHypersensitivity skin testingImmune responseImmunocompromised HostInflammation MediatorsInternationalInvestigational New Drug ApplicationJAK1 geneLeadLegal patentLengthLesionMelanocortin 1 ReceptorMelanogenesisMethotrexateMusOrganOxidation-ReductionPathologyPathway interactionsPatientsPenetrationPhasePhysiologicalPigmentation physiologic functionPopulationProliferatingProteinsPsyche structurePsychological StressQuality of lifeReactive Oxygen SpeciesReadingRecurrenceReportingResearchSafetySkinSkin PigmentationSkin SubstitutesStigmatizationStratum BasaleTacrolimusTemperatureTestingTherapeuticTimeTopical CorticosteroidsTopical applicationToxic effectTreatment outcomeUltraviolet B RadiationUncertaintyUnited States Food and Drug AdministrationVitiligoWomanalpha-Melanocyte stimulating hormoneanalogbiological adaptation to stressburden of illnesscommercializationcorticosteroid inhibitorefficacy evaluationefficacy validationexpectationimmunomodulatory therapiesin vivoinhibitorliquid chromatography mass spectrometrymelanocyteneoantigensnovelphase 2 studypre-clinicalpsychologicreceptorside effectskin colorskin lesionsocial stigmasuccesssuicide ratetherapy outcomeultravioletyoung adult
项目摘要
PROJECT SUMMARY
Vitiligo is the most common acquired hypopigmentary disorder that afflicts 0.5-2% of the world population, from
all ethnicities and skin color. It is characterized by loss of melanocytes, which is often progressive, resulting in
depigmented skin lesions. Vitiligo can be segmental (5-16% of all cases) or most commonly, non-segmental. It
is a disease of young adults, as 25% of all non-segmental vitiligo patients develop the disease by age 10, and
50% develop it by age 30. Vitiligo is erroneously perceived to be merely cosmetically disfiguring and not life-
threating. However, in addition to other pathologies, such as alopecia areata and Hashimoto’s thyroiditis, the
disease carries with it a tremendous psychological burden and social stigma, and a high rate of suicide,
particularly in patients with skin of color. Repigmentation of vitiligo skin is difficult, time-consuming, and
unpredictable. Even after successful repigmentation, there is 40% chance of recurrence of loss of pigmentation,
which adds to the patients’ anxiety and mental anguish. Multiple mechanisms have been proposed for
melanocyte destruction in vitiligo, including autoimmune response, generation of inflammatory mediators,
genetic factors, pro-oxidant state in skin, and intrinsic melanocyte abnormalities and detachment. The immune
response can be either the primary cause of melanocyte destruction or can be secondarily activated by neo-
antigens expressed on melanocytes. We hypothesize that persistent and more rapid repigmentation of
vitiligo skin will be achieved by targeting the melanocortin 1 receptor (MC1R) expressed on human
melanocytes by topical application of a superpotent and selective agonist. The PI has reported that
activation of MC1R expressed on human melanocytes by the physiological agonist α-melanocyte stimulating
hormone (α-MSH) promotes melanocyte proliferation, attachment, survival, normal redox state and
melanogenesis. These findings led her to develop potent tetrapeptide analogs of α-MSH that mimic its function
in human melanocytes. Her major goal is to develop one of these tetrapeptide analogs, LK 184, which is highly
selective for MC1R and 10-fold more potent than α-MSH, in a topical formulation to treat depigmented vitiligo
lesions. The Specific Aims are to develop LK 184 in an optimal topical formulation and provide preclinical ex vivo
and in vivo evidence of its efficacy and safety in stimulating long lasting pigmentation. The efficacy of LK 184 is
supported by her data, and by reported clinical trials showing that the full length α-MSH analog NDP- α-MSH
enhances repigmentation of vitiligo skin, when combined with narrow band UVB. However, NDP- α-MSH is not
selective to MC1R, has extracutaneous effects, and has to be administered systemically. The expectations are
that use of the first in class agent, LK 184, in combination with other existing treatments will have a huge positive
impact on the quality of life of vitiligo patients, and limit the use of potentially dangerous immunosuppressives.
The proposed studies will satisfy many requirements for regulatory approval of commercialization of LK 184 for
vitiligo treatment by MC1R Ventures LLC.
项目总结
白癜风是最常见的获得性色素减退疾病,世界上0.5%-2%的人口受到这种疾病的困扰。
所有种族和肤色。它的特点是黑素细胞的丧失,这通常是进行性的,导致
脱色的皮肤损伤。白癜风可以是节段性的(占所有病例的5%-16%),也可以是最常见的非节段性白癜风。它
是一种年轻人的疾病,因为25%的非节段性白癜风患者在10岁之前会患上这种疾病,并且
50%的人在30岁之前会患上这种病。白癜风被错误地认为只是美观的毁容,而不是生活-
威胁。然而,除了斑秃和桥本甲状腺炎等其他疾病外,
疾病带来了巨大的心理负担和社会耻辱,自杀率很高,
尤其是肤色不同的患者。白癜风皮肤的重新色素沉着是困难、耗时和
变幻莫测。即使在成功地重新着色后,也有40%的机会复发,
这增加了患者的焦虑和精神痛苦。已经提出了多种机制来实现
白癜风的黑素细胞破坏,包括自身免疫反应,炎性介质的产生,
遗传因素,皮肤中的促氧化状态,以及固有的黑素细胞异常和脱落。免疫者
反应可以是破坏黑素细胞的主要原因,也可以是由neo-2激活的。
黑素细胞上表达的抗原。我们假设,持续和更快的色素沉着
白癜风皮肤将通过靶向人类表达的黑素皮质素1受体(MC1R)来实现
黑素细胞通过局部应用一种超强而选择性的激动剂。私家侦探报告说
生理激动剂α-黑素细胞刺激剂对人黑素细胞表达的MC1R的激活作用
激素(α-MSH)促进黑素细胞的增殖、附着、存活、正常氧化还原状态和
黑色素生成。这些发现促使她开发出有效的α-MSH四肽类似物来模拟其功能
在人类黑素细胞中。她的主要目标是开发这些四肽类似物之一,LK 184,它具有高度的
在治疗脱色素白癜风的局部配方中,对MC1R具有选择性,比α-MSH有效10倍
损伤。具体目标是以最佳局部配方开发LK 184,并提供临床前体外试验
以及体内证据表明,它在刺激持久色素沉着方面的有效性和安全性。LK 184的疗效是
她的数据和报道的临床试验表明,全长α-MSH类似物NdP-α-MSH
增强白癜风皮肤的再色素沉着,当与窄波段UVB联合使用时。然而,ndp-α-msh不是
对MC1R有选择性,具有皮外效应,必须全身给药。人们的期望是
将第一类药物LK 184与其他现有治疗方法结合使用将产生巨大的积极影响
影响白癜风患者的生活质量,并限制潜在危险的免疫抑制剂的使用。
拟议的研究将满足监管部门批准LK 184商业化的许多要求
MC1R Ventures LLC治疗白癜风
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 }}
ZALFA ABDEL-MALEK其他文献
ZALFA ABDEL-MALEK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 }}
{{ truncateString('ZALFA ABDEL-MALEK', 18)}}的其他基金
Targeting the Melanocortin 1 Receptor by Selective Small Analogs of α-Melanocortin for Melanoma Prevention
通过选择性α-黑皮质素小类似物靶向黑皮质素 1 受体预防黑色素瘤
- 批准号:
10474302 - 财政年份:2018
- 资助金额:
$ 29.59万 - 项目类别:
Targeting the Melanocortin 1 Receptor by Selective Small Analogs of α-Melanocortin for Melanoma Prevention
通过选择性α-黑皮质素小类似物靶向黑皮质素 1 受体预防黑色素瘤
- 批准号:
10265379 - 财政年份:2018
- 资助金额:
$ 29.59万 - 项目类别:
Targeting the Melanocortin 1 Receptor by Selective Small Analogs of α-Melanocortin for Melanoma Prevention
通过选择性α-黑皮质素小类似物靶向黑皮质素 1 受体预防黑色素瘤
- 批准号:
9898307 - 财政年份:2018
- 资助金额:
$ 29.59万 - 项目类别:
Melanoma prevention by MC1R selective small peptide analogs of alpha MSH
通过 MC1R 选择性 α MSH 小肽类似物预防黑色素瘤
- 批准号:
9105353 - 财政年份:2015
- 资助金额:
$ 29.59万 - 项目类别:
Melanoma prevention by MC1R selective small peptide analogs of alpha MSH
通过 MC1R 选择性 α MSH 小肽类似物预防黑色素瘤
- 批准号:
8958319 - 财政年份:2015
- 资助金额:
$ 29.59万 - 项目类别:
How p16 and MC1R mutations synergistically exacerbate melanoma risk.
p16 和 MC1R 突变如何协同加剧黑色素瘤风险。
- 批准号:
8652005 - 财政年份:2014
- 资助金额:
$ 29.59万 - 项目类别:
Impact of MC1R Functional Variants on the DNA Damage Response of Human Melanocyte
MC1R 功能变异对人黑素细胞 DNA 损伤反应的影响
- 批准号:
7730250 - 财政年份:2009
- 资助金额:
$ 29.59万 - 项目类别:
Impact of MC1R Functional Variants on the DNA Damage Response of Human Melanocyte
MC1R 功能变异对人黑素细胞 DNA 损伤反应的影响
- 批准号:
8462256 - 财政年份:2009
- 资助金额:
$ 29.59万 - 项目类别:
Signaling Pathways for UV-Induced Melanogenic Response
紫外线诱导的黑色素生成反应的信号通路
- 批准号:
7902757 - 财政年份:2009
- 资助金额:
$ 29.59万 - 项目类别:
Impact of MC1R Functional Variants on the DNA Damage Response of Human Melanocyte
MC1R 功能变异对人黑素细胞 DNA 损伤反应的影响
- 批准号:
8274543 - 财政年份:2009
- 资助金额:
$ 29.59万 - 项目类别:
相似海外基金
How tensins transform focal adhesions into fibrillar adhesions and phase separate to form new adhesion signalling hubs.
张力蛋白如何将粘着斑转化为纤维状粘连并相分离以形成新的粘连信号中枢。
- 批准号:
BB/Y004841/1 - 财政年份:2024
- 资助金额:
$ 29.59万 - 项目类别:
Research Grant
Defining a role for non-canonical mTORC1 activity at focal adhesions
定义非典型 mTORC1 活性在粘着斑中的作用
- 批准号:
BB/Y001427/1 - 财政年份:2024
- 资助金额:
$ 29.59万 - 项目类别:
Research Grant
How tensins transform focal adhesions into fibrillar adhesions and phase separate to form new adhesion signalling hubs.
张力蛋白如何将粘着斑转化为纤维状粘连并相分离以形成新的粘连信号中枢。
- 批准号:
BB/Y005414/1 - 财政年份:2024
- 资助金额:
$ 29.59万 - 项目类别:
Research Grant
Development of a single-use, ready-to-use, sterile, dual chamber, dual syringe sprayable hydrogel to prevent postsurgical cardiac adhesions.
开发一次性、即用型、无菌、双室、双注射器可喷雾水凝胶,以防止术后心脏粘连。
- 批准号:
10669829 - 财政年份:2023
- 资助金额:
$ 29.59万 - 项目类别:
Regulating axon guidance through local translation at adhesions
通过粘连处的局部翻译调节轴突引导
- 批准号:
10587090 - 财政年份:2023
- 资助金额:
$ 29.59万 - 项目类别:
Improving Maternal Outcomes of Cesarean Delivery with the Prevention of Postoperative Adhesions
通过预防术后粘连改善剖宫产的产妇结局
- 批准号:
10821599 - 财政年份:2023
- 资助金额:
$ 29.59万 - 项目类别:
Regulating axon guidance through local translation at adhesions
通过粘连处的局部翻译调节轴突引导
- 批准号:
10841832 - 财政年份:2023
- 资助金额:
$ 29.59万 - 项目类别:
Prevention of Intraabdominal Adhesions via Release of Novel Anti-Inflammatory from Surface Eroding Polymer Solid Barrier
通过从表面侵蚀聚合物固体屏障中释放新型抗炎剂来预防腹内粘连
- 批准号:
10532480 - 财政年份:2022
- 资助金额:
$ 29.59万 - 项目类别:
I-Corps: A Sprayable Tissue-Binding Hydrogel to Prevent Postsurgical Cardiac Adhesions
I-Corps:一种可喷雾的组织结合水凝胶,可防止术后心脏粘连
- 批准号:
10741261 - 财政年份:2022
- 资助金额:
$ 29.59万 - 项目类别:
Sprayable Polymer Blends for Prevention of Site Specific Surgical Adhesions
用于预防特定部位手术粘连的可喷涂聚合物共混物
- 批准号:
10674894 - 财政年份:2022
- 资助金额:
$ 29.59万 - 项目类别:














{{item.name}}会员




