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Methods and compositions relating to lung repair

A technology of lung tissue and alveoli, which is used in drug combinations, medical preparations containing active ingredients, drug delivery, etc.

Pending Publication Date: 2020-11-06
CHILDRENS MEDICAL CENT CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, as shown here, sFlt1 functions in surprising and unexpected ways in the growth and repair of lung tissue, in stark contrast to previously described activities in tumors and liver

Method used

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  • Methods and compositions relating to lung repair
  • Methods and compositions relating to lung repair
  • Methods and compositions relating to lung repair

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach

[0162] CLAIMS 1. A method of inducing growth and / or repair of lung tissue, the method comprising contacting the lung tissue with an agonist of sFlt1-Hif signaling.

[0163] 2. A method of inducing growth and / or repair of lung tissue in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an sFltl-Hif signaling agonist.

[0164] 3. The method of paragraph 2, wherein the growth and / or repair of lung tissue is compensatory lung growth.

[0165] 4. The method according to any of paragraphs 2-3, wherein the subject is suffering from severe pulmonary hypoplasia, pulmonary hypoplasia disease, congenital diaphragmatic hernia, bronchopulmonary dysplasia, emphysema, with Subjects with disease of insufficient alveolar count, alveolar capillary hypoplasia, or who have undergone lung resection.

[0166] 5. The method of any of paragraphs 2-4, wherein the subject has not been diagnosed with, or in need of treatment for, an infl...

Embodiment 1

[0184]After left pneumonectomy, C57B16 mice were randomized to receive daily intraperitoneal injections of saline or soluble fms-like tyrosine kinase 1 (sFlt1 ) at a dose of 20 mcg / kg. On postoperative day 4, mice were subjected to lung function studies and then euthanized for lung volume measurements. Lung volumes were measured by the water displacement method. Mice treated with sFlt1 exhibited significantly higher lung volume (p Figure 1-Figure 4 ). In patients with severe lung hypoplasia, the therapy could potentially improve lung growth and lung function.

[0185] Soluble VEGF receptors bind (sFlt1) VEGF and consume circulating VEGF molecules. The sFlt1 molecule has been shown to inhibit tumor and liver regeneration. However, an unexpected finding was that soluble VEGF receptors accelerated compensatory lung growth after pneumonectomy. This is of interest for children with disorders of lung hypoplasia, such as those with congenital diaphragmatic hernias.

Embodiment 2

[0187] according to Figure 6 The depicted experimental design administered sFlt1 to mice. The results demonstrated that, contrary to expectations, administration of sFlt1 increased lung growth ( Figure 10 ). The dose response of sFlt1 was studied ( Figure 8 ), in mice, 20mcg / kg of sFlt1 is the optimal dosing regimen ( Figure 9 ). It was also demonstrated that administration of sFlt1 improved lung compliance and inspiratory capacity, which is consistent with the lung volume data ( Figure 10 ).

[0188] Further studies demonstrated that administration of sFlt1 unexpectedly increased the levels of both VEGF and HIF-2α ( Figure 11 , Figure 12 ), suggesting that sFlt1 increases endogenous production of VEGF by upregulating HIF-2α. The effect of the HIF-2α inhibitor PT-2385 on the administration of sFlt1 was determined ( Figure 14 ), and showed that inhibition of HIF-2α attenuated the effect of sFlt1 on lung growth ( Figure 15 ) and the exercise tolerance of the s...

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Abstract

The technology described herein is directed to methods of inducing and / or enhancing lung growth and / or repair.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Application No. 62 / 646,493, filed March 22, 2018, the contents of which are hereby incorporated by reference in their entirety. [0003] sequence listing [0004] This application contains a Sequence Listing, which has been filed electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on January 24, 2019, is named 701039-090440WOPT_SL.txt and is 87,789 bytes in size. technical field [0005] The techniques described herein relate to methods of inducing growth and / or repair of lung tissue. Background technique [0006] Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis and tissue growth. Previously, the soluble VEGF receptor (sFlt1) was shown to deplete circulating VEGF, thereby suppressing tumor growth and inhibiting liver regeneration. However, as shown ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/18A61P11/00A61K38/17A61K9/00A61K31/472
CPCA61K9/0019A61K9/007A61K31/437A61K31/472A61K31/506A61K31/515A61K38/179A61P11/00A61K9/0014A61K31/513A61K38/177
Inventor 马克·布德迪伊·T·达奥
Owner CHILDRENS MEDICAL CENT CORP
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