Ostreolysin Modulates Brown Adipose Tissue to Treat Steatohepatitis

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Solution Overview

Problem

Current treatments for obesity, metabolic syndrome, fatty liver disease, and cancer are challenging due to the complexity of these diseases, with limited effective therapies available, particularly for conditions like non-alcoholic fatty liver disease and colorectal cancer, and there is a need for molecules that can increase energy expenditure and suppress cancer cell proliferation.

Innovation Solution

The use of ostreolysin, a protein or its functionally related variants, administered as a pharmaceutical or nutraceutical composition, to treat, prevent, or reduce the severity of conditions associated with metabolic syndrome, including fatty liver, non-alcoholic fatty liver disease, and cancer, by enhancing brown adipose tissue activity and inducing apoptosis in cancer cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional treatments are used for obesity and metabolic syndrome, then some symptomatic relief may be achieved, but the complexity of the diseases limits effective therapy and does not address the underlying mechanisms of energy homeostasis

Engineering Contradiction:
Improveeffectiveness of therapyVSAvoidphysiological and biochemical complexity of the disease
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies preliminary action by administering ostreolysin before the full development of metabolic complications, aiming to prevent rather than merely treat. The compound is shown to prevent obesity development and metabolic syndrome progression when given in advance, addressing the underlying energy homeostasis mechanisms before pathological changes become irreversible.

Inventive Principle:
Principle #10Preliminary action

2Use of energy by moving object

If brown adipose tissue activity is increased to enhance energy expenditure, then obesity and metabolic syndrome can be combated, but human adults do not have sufficient amounts of active BAT

Engineering Contradiction:
Improveenergy expenditureVSAvoidamount of brown adipose tissue
Core Design Contradiction:
Use of energy by moving objectVSQuantity of substance

Solution Approach 1:

The patent applies parameter changes by using ostreolysin to fundamentally alter the functional state of brown adipose tissue in adult humans. The compound increases BAT activity and energy expenditure parameters despite the limited quantity of BAT present, effectively changing the metabolic parameters of adult humans to resemble those with higher BAT activity.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If pharmacotherapy is developed to reverse steatohepatitis, then liver function can be improved, but currently no pharmacotherapy is available that can fully reverse or prevent steatohepatitis

Engineering Contradiction:
Improveability to reverse steatohepatitisVSAvoidavailability of pharmacotherapy
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent applies the taking out principle by isolating and utilizing the specific anti-steatohepatitis activity of ostreolysin from its source organism. The compound is purified and characterized as a discrete pharmacological agent that can be administered to reverse steatohepatitis, extracting the therapeutic function from the natural source and making it available as a standalone medication.

Inventive Principle:
Principle #2Taking out (Extraction)

4Reliability

If molecules are identified that can suppress cancer cell proliferation, then cancer treatment can be improved, but the complexity of cancer mechanisms makes identifying such molecules challenging

Engineering Contradiction:
Improveability to suppress cancer cell proliferationVSAvoidcomplexity of cancer mechanisms
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies the intermediary principle by using ostreolysin as a mediator that acts on cancer cells through specific mechanisms (inducing apoptosis, affecting energy metabolism) without requiring direct manipulation of complex cancer signaling pathways. The compound serves as an intermediary agent that translates into anti-cancer effects through multiple downstream mechanisms, simplifying the therapeutic approach despite cancer's complexity.

Inventive Principle:
Principle #24Intermediary (Mediator)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

Ostreolysin effectively reduces body weight, improves liver function, decreases glucose intolerance, and suppresses cancer cell growth, demonstrating significant therapeutic potential for metabolic and cancer-related disorders.

Implementation Method 1

inducing apoptosis in cancer cells

Methodology Applied
Scientific EffectApoptosis:

Implementation Method 2

the uncoupling of mitochondrial respiration in brown adipose tissue (BAT). In this process, there is a regulated proton leak in the inner mitochondrial membrane through uncoupling protein 1 (UCP1), resulting in the dissipation of energy as heat

Methodology Applied
Scientific EffectUncoupling of mitochondrial respiration:

Data Source

PatentEP3257520B1Ostreolysin for use in the treatment of steatohepatitis
Publication Date: 2020.01.29 YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM LTD
  • EP3257520B1 patent drawingFigure 1~2
  • EP3257520B1 patent drawingFigure 3~4
  • EP3257520B1 patent drawingFigure 5A~5B

AI summary

A formulation comprising oly, oly functionally related variant or combination thereof, for use in treating, preventing or reducing the severity of one or more conditions or complications associated with metabolic syndrome.