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Prevention and treatment of inflammatory conditions

A technology for inflammatory conditions, hepatitis, applied in the field of compositions that modulate type II and/or type I NKT cells, and can solve problems such as the lack of effective treatment methods for the disease

Active Publication Date: 2017-09-26
GRI BIO INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Despite progress in some areas, effective treatments to halt the disease are still lacking

Method used

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  • Prevention and treatment of inflammatory conditions
  • Prevention and treatment of inflammatory conditions
  • Prevention and treatment of inflammatory conditions

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Experimental program
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Effect test

Embodiment 1

[0535] Miltefosine was able to stimulate the type II NKT cell hybridoma Hy19.3 in a plate-bound CDld assay. CDld protein-coated 96-well plates were incubated with the indicated liquids for 6 hr, washed and added with type II NKT cells Hy 19.3 (50,000 cells / well), and IL-2 in the supernatant was measured after 16 hr. LSF, lysosulfatidyl; LPC, lysophosphatidylcholine.

[0536] These data show that miltefosine, an analog of lysophosphatidylcholine (LPC), can bind CDld molecules and stimulate type II NKT cells.

Embodiment 2

[0538] Naive B6 mice were treated daily for 7 days with DMSO (control) or miltefosine 1 mg (dissolved in DMSO and diluted into PBS) by oral gavage. Splenocytes were cultured in vitro for 90 hr in the presence or absence of α-GalCer. Stimulation (as a stimulation index) and expansion (using α-GalCer / CD1d) of type I NKT cells at a concentration of α-GalCer of 10 ng / ml - Tetramer + cells, as FACS staining), are shown in Figure 2A with Figure 2B middle.

[0539] Figure 2A with Figure 2B The data in show that there is a marked inhibition of type I NKT cell proliferation and expansion in the presence of its cognitive ligand α-GalCer in miltefosine-treated animals.

[0540] These data are consistent with the fact that other lipids such as sulfatides (glycolipids) or lysophosphatidylcholines (LPC, phospholipids) activate type II NKT cells, leading to inactivation or inhibition of type I NKT cells.

Embodiment 3

[0542] 12 hr before ConA administration, DMSO / PBS or miltefosine was administered to the BL / 6 mouse group, and liver injury was determined by H&E staining of liver sections and detection of liver enzymes (such as ALT in serum) after 24 hr ( Figure 3A and Figure 3B ). Data shown represent 2 independent experiments.

[0543] like Figure 3B As shown, in liver sections treated with con A, staining indicative of necrosis (red H&E staining)1 was observed, but in liver sections treated with con A and miltefosine, staining indicative of attenuated necrosis was observed (diminished red H&E staining)2.

[0544] Thus, suppression of ConA-induced hepatitis was observed following treatment with miltefosine. These data show that, similar to sulfatide or LPC, treatment of mice with miltefosine resulted in a significant inhibition of liver injury following Con A injection.

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Abstract

In accordance with some embodiments herein, methods and compositions for prevention and treatment of inflammatory conditions are provided. In some embodiments, compositions comprising NKT-2 activators, for example miltefosine are provided. In some embodiments, the compositions further comprise sulfatide and / or a RAR agonist. In some embodiments, the compositions comprise activators of Type II NKT cells, and / or inhibitors of Type I NKT cells.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Provisional Patent Application No. 62 / 089,690, entitled "Prevention and Treatment of Inflammatory Conditions," filed December 9, 2014, which is hereby incorporated by reference in its entirety. Background of the invention [0003] field [0004] Some embodiments herein relate to compositions and methods for modulating type II and / or type I NKT cells in the prevention and treatment of liver inflammatory conditions. [0005] Description of related fields [0006] Excessive alcohol consumption is the leading cause of liver disease in the Western world. Evidence of liver damage was observed in individuals who consumed four or more alcoholic beverages per day (for men, four 12-ounce glasses of beer, four glasses of wine, or four ounces of spirits; or for women, half the amount). Although it is not fully understood how alcohol damages the liver, chronic alcohol consumption results i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K31/685A61K31/661A61P29/00A61P1/16A61P3/10A61P9/10A61P37/02A61P19/02A61P1/00
CPCA61K31/661A61K31/685A61K45/00A61K39/4621A61K2239/31A61K39/46433A61K39/4611A61K31/4436A61K31/7028A61P1/00A61P1/04A61P1/06A61P1/16A61P19/02A61P21/02A61P25/00A61P29/00A61P31/14A61P31/20A61P37/02A61P37/06A61P43/00A61P9/10A61P3/10A61K31/202A61K35/17Y02A50/30
Inventor 维平·库马·查图维迪
Owner GRI BIO INC
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