Delving into the Latest Updates on Heat shock protein 10(Invion Ltd.) with Synapse

Overview

Basic Info

Drug Type

Recombinant protein

Synonyms

Chaperonin 10, Chaperonin-10, Heat shock protein 10

+ [10]

Target-

Action

modulators

Mechanism

Immunomodulators

Therapeutic Areas

Immune System DiseasesNervous System DiseasesDigestive System Disorders+ [2]

Active Indication

Colitis, UlcerativeMultiple SclerosisPsoriasis+ [2]

Inactive Indication

Plaque psoriasis

Originator Organization

Invion Ltd.

Active Organization

Invion Ltd.

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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BACKGROUNDSystemic lupus erythematosus (SLE) is still treated with global immunosuppressants with serious toxicities. We hypothesized that endogenous immunosuppressive molecules might be able to control SLE manifestations more specifically. Heat shock protein 10, or chaperonin 10 (Cpn10), is a secretory molecule that can suppress innate and adaptive immunity.METHODSRecombinant human Cpn10 (100 μg per mouse) was given intraperitoneally to healthy-appearing female MRL-(Fas)lpr mice from 12 to 22 weeks of age. At the age of 22 weeks, mice were analysed for treatment outcome by harvesting organs, plasma and urine.RESULTSCpn10 entirely prevented cutaneous lupus lesions as compared to vehicle-treated mice. Cpn10 also suppressed lupus nephritis as evident from serum creatinine levels, albuminuria and the scores of disease activity and chronicity. Autoimmune lung disease was unaffected by Cpn10 treatment while overall survival of mice was prolonged. Cpn10 did not have any major effects on either dendritic cell or B-cell counts except T cells in spleen, plasma interferon-gamma, tumour necrosis factor-alpha, interleukin-10, anti-nuclear autoantibody levels or markers of lymphoproliferation.CONCLUSIONSIn summary, recombinant Cpn10 selectively prevents cutaneous lupus and suppresses nephritis in MRL-(Fas)lpr mice without affecting the underlying systemic autoimmune process. Hence, Cpn10 might be useful for the treatment of skin and kidney manifestations of SLE.

01 May 2009·Journal of Cellular PhysiologyQ2 · BIOLOGY

Chaperonin 10 as an endothelial‐derived differentiation factor: Role of glycogen synthase kinase‐3

Q2 · BIOLOGY

Article

Author: Monica C. Dobocan ; Gulzhakhan Sadvakassova ; Luis F. Congote

AbstractThe anti‐inflammatory peptide early pregnancy factor/chaperonin 10 (cpn10) was identified by 2D‐electrophoresis/mass spectrometry as one of the proteins increased in human umbilical cord endothelial cells (HUVEC) after treatment with erythropoietin (EPO). EPO increased the amount of cpn10 released into the medium of HUVEC cultures, despite the absence of a secretory signal peptide. Although immunosupressive agents would represent an indirect advantage for red cell formation under conditions of infection and inflammation, it is possible that cpn10 may have direct effects on erythroid cells. We show that the chaperonin decreased cell proliferation in cultures of the erythroleukemia cell line K562 and increased the amounts of the erythroid differentiation markers glycophorin A and hemoglobin in TF‐1 cells. Nevertheless, cpn10 is not a specific erythroid cell differentiation factor, because monolayers of skin fibroblasts overexpressing cpn10 had significantly higher levels of the differentiation marker collagen I than normal fibroblasts. Nothing is known about the mechanism of action of cpn10 in its capacity as a general differentiation factor. An analysis of early changes taking place in K562 cells after incubation with cpn10 using antibody microarrays identified several phosphorylation events, including a decrease of GSK‐3α phosphorylation. Further studies in TF‐1 cells indicated that cpn10 decreased the phosphorylation of cofilin‐1 while stimulating that of GSK‐3β. Furthermore, glycophorin A production decreased in the presence of a GSK‐3 inhibitor in the same cells. These experiments support the idea that GSK‐3‐regulated signal transduction pathways are not only important for stem cell maintenance but may be involved in events controlling cell differentiation. J. Cell. Physiol. 219: 470–476, 2009. © 2009 Wiley‐Liss, Inc.

01 Mar 2009·Multiple Sclerosis JournalQ2 · MEDICINE

Results of a phase IIa clinical trial of an anti-inflammatory molecule, chaperonin 10, in multiple sclerosis

Q2 · MEDICINE

Article

Author: Kneebone, C ; Broadley, SA ; Coulthard, A ; Williams, B ; Griffiths, L ; Shakib, S ; Johnson, B ; Brown, G ; Feeney, D ; Vanags, D ; Mullins, P

Background Chaperonin 10 (Cpn10) is a mitochondrial molecule involved in protein folding. The aim of this study was to determine the safety profile of Cpn10 in patients with multiple sclerosis (MS). Methods A total of 50 patients with relapse-remitting or secondary progressive MS were intravenously administered 5 mg or 10 mg of Cpn10 weekly for 12 weeks in a double-blind, randomized, placebo controlled, phase II trial. Clinical reviews, including Expanded Disability Status Scale and magnetic resonance imaging (MRI) with Gadolinium, were undertaken every 4 weeks. Stimulation of patient peripheral blood mononuclear cells with lipopolysaccharide ex vivo was used to measure the in vivo activity of Cpn10. Results No significant differences in the frequency of adverse events were seen between treatment and placebo arms. Leukocytes from both groups of Cpn10-treated patients produced significantly lower levels of critical proinflammatory cytokines. A trend toward improvement in new Gadolinium-enhancing lesions on MRI was observed, but this difference was not statistically significant. No differences in clinical outcome measures were seen. Conclusions Cpn10 is safe and well tolerated when administered to patients with MS for 3 months, however, a further extended phase II study primarily focused on efficacy is warranted.

100 Deals associated with Heat shock protein 10(Invion Ltd.)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Colitis, Ulcerative	Phase 2	-	Invion Ltd.	-
Multiple Sclerosis	Phase 2	-	Invion Ltd.	-
Psoriasis	Phase 2	-	Invion Ltd.	-
Rheumatoid Arthritis	Phase 2	-	Invion Ltd.	-
Systemic Lupus Erythematosus	Phase 2	-	Invion Ltd.	-
Colitis, Ulcerative	Preclinical	Australia	-	-
Multiple Sclerosis	Preclinical	Australia	Invion Ltd.	-
Plaque psoriasis	Preclinical	Australia	Invion Ltd.	-
Rheumatoid Arthritis	Preclinical	Australia	Invion Ltd.	-
Rheumatoid Arthritis	Preclinical	New Zealand	Invion Ltd.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01838694 (CTgov)	Phase 1/2	Systemic Lupus Erythematosus	30	Placebo (Placebo)	rxlnagjljd(hrekukfimx) = ydvzlrukmb ikpxqtyqzz (jwovtraprc, cdtbsswost - oxyrsueopx) View more	-	30 Jan 2017
				Ala-Cpn10 (Ala-Cpn10)	mfmdmdimzm(vesrnivkpz) = vvnqibbugv hbjnyuqfvj (xbufcpjlob, wawymyqvbu - dpnwfjflkf) View more

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