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概览

疾病领域	数量

神经系统疾病	1

排名前五的药物类型	数量

未知	1
小分子化药	1
化学药	1

排名前五的靶点	数量

COX-1 x COX-2	1

关联

3

项与 Layerbio, Inc. 相关的药物

Ketorolac

酮咯酸

靶点

COX-1 x COX-2

作用机制

COX-1抑制剂 [+1]

在研机构

Layerbio, Inc. [+1]

原研机构

Neumentum, Inc.初创企业

在研适应症

术后疼痛 [+1]

非在研适应症-

最高研发阶段临床3期

首次获批国家/地区-

首次获批日期-

LB-100(Layerbio)

靶点-

作用机制-

在研机构

Layerbio, Inc.

原研机构

Layerbio, Inc.

在研适应症

青光眼

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

LB-210

靶点-

作用机制-

在研机构

Layerbio, Inc.

原研机构

Layerbio, Inc.

在研适应症

创伤和损伤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

1

项与 Layerbio, Inc. 相关的临床试验

ISRCTN10336649 / Completed临床1期

Pilot study to assess safety and efficacy of OcuRing-K™ ketorolac implant for cataract surgery

开始日期2019-12-03

申办/合作机构

Layerbio, Inc.

100 项与 Layerbio, Inc. 相关的临床结果

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0 项与 Layerbio, Inc. 相关的专利（医药）

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1

项与 Layerbio, Inc. 相关的文献（医药）

2019-01-01·Tissue Engineering Part A2区 · 医学

Acceleration of Diabetic Wound Healing with PHD2- and miR-210-Targeting Oligonucleotides

2区 · 医学

Article

作者: Gurtner, Geoffrey C. ; Stern-Buchbinder, Zachary A. ; Dallas, Anne ; Kosaric, Nina ; Barrera, Janos A. ; Engel, Karl ; Ilves, Heini ; Bonham, Clark A. ; Trotsyuk, Artem ; Hammond, Paula T. ; Mansbridge, Jonathan ; Rodrigues, Melanie ; Jayasena, Sumedha ; Johnston, Brian H. ; White, Aleksandr ; Mandell, Kenneth J.

In diabetes-associated chronic wounds, the normal response to hypoxia is impaired and many cellular processes involved in wound healing are hindered. Central to the hypoxia response is hypoxia-inducible factor-1α (HIF-1α), which activates multiple factors that enhance wound healing by promoting cellular motility and proliferation, new vessel formation, and re-epithelialization. Prolyl hydroxylase domain-containing protein 2 (PHD2) regulates HIF-1α activity by targeting it for degradation under normoxia. HIF-1α also upregulates microRNA miR-210, which in turn regulates proteins involved in cell cycle control, DNA repair, and mitochondrial respiration in ways that are antagonistic to wound repair. We have identified a highly potent short synthetic hairpin RNA (sshRNA) that inhibits expression of PHD2 and an antisense oligonucleotide (antimiR) that inhibits miR-210. Both oligonucleotides were chemically modified for improved biostability and to mitigate potential immunostimulatory effects. Using the sshRNA to silence PHD2 transcripts stabilizes HIF-1α and, in combination with the antimiR targeting miR-210, increases proliferation and migration of keratinocytes in vitro. To assess activity and delivery in an impaired wound healing model in diabetic mice, PHD2-targeting sshRNAs and miR-210 antimiRs both alone and in combination were formulated for local delivery to wounds using layer-by-layer (LbL) technology. LbL nanofabrication was applied to incorporate sshRNA into a thin polymer coating on a Tegaderm mesh. This coating gradually degrades under physiological conditions, releasing sshRNA and antimiR for sustained cellular uptake. Formulated treatments were applied directly to splinted full-thickness excisional wounds in db/db mice. Cellular uptake was confirmed using fluorescent sshRNA. Wounds treated with a single application of PHD2 sshRNA or antimiR-210 closed 4 days faster than untreated wounds, and wounds treated with both oligonucleotides closed on average 4.75 days faster. Markers for neovascularization and cell proliferation (CD31 and Ki67, respectively) were increased in the wound area following treatment, and vascular endothelial growth factor (VEGF) was increased in sshRNA-treated wounds. Our results suggest that silencing of PHD2 and miR-210 either together or separately by localized delivery of sshRNAs and antimiRs is a promising approach for the treatment of chronic wounds, with the potential for rapid clinical translation.

100 项与 Layerbio, Inc. 相关的药物交易

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100 项与 Layerbio, Inc. 相关的转化医学

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