Alpha B-crystallin Therapy for Multiple Sclerosis

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Solution Overview

Problem

Current treatments for multiple sclerosis and other inflammatory diseases, such as rheumatoid arthritis and Alzheimer's, are inadequate in managing disease progression and relapses, with existing therapies only partially effective in reducing inflammation and cell damage.

Innovation Solution

Administration of alpha B-crystallin protein or nucleic acids that enhance alpha B-crystallin levels to suppress or prevent the initiation, progression, or relapses of inflammatory diseases by inhibiting inflammatory pathways and promoting cell survival in the CNS.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current immunomodulatory therapies (interferons, glatiramer acetate, immunosuppressants) are used to treat multiple sclerosis, then frequency of acute exacerbations is decreased and eventual disability is delayed, but the therapies are only partially effective in managing disease progression and relapses

Engineering Contradiction:

Improveeffectiveness in managing disease progressionVSAvoidfrequency of exacerbations

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

Alpha B-crystallin acts as a molecular chaperone and intermediary protein that binds to unfolded and denatured proteins, preventing their aggregation and promoting proper folding. This chaperone activity mediates protection against protein misfolding and aggregation in MS, addressing the incomplete effectiveness of current therapies by introducing a new mechanism of action that complements existing immunomodulatory approaches

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the therapeutic parameter from purely immunomodulatory mechanisms to include molecular chaperone activity and protein homeostasis regulation. By administering alpha B-crystallin protein or nucleic acids that enhance its levels, the therapy introduces a new biochemical parameter (chaperone-mediated protein folding) that addresses disease progression through a different mechanism than current immunosuppressants

Inventive Principle:

Principle #35Parameter changes

2Duration of action of moving object

If corticosteroids are administered to treat acute exacerbations, then the duration of acute attacks is shortened, but long-term outcome is not affected

Engineering Contradiction:

Improveduration of acute attacksVSAvoidlong-term outcome

Core Design Contradiction:

Duration of action of moving objectVSReliability

Solution Approach 1:

Alpha B-crystallin provides preliminary protective action by preventing protein misfolding and aggregation before they occur. As a molecular chaperone, it proactively maintains protein homeostasis and protects against cellular stress, addressing long-term disease progression rather than merely treating acute symptoms after they manifest

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The invention converts the harmful accumulation of misfolded proteins into a beneficial therapeutic target. By administering alpha B-crystallin to enhance the cell's natural chaperone capacity, the therapy transforms the problem of protein aggregation (which contributes to neuronal damage in MS) into a therapeutic opportunity, where increased chaperone activity prevents the harmful aggregation process

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

3Reliability

If immunosuppressants are used for severe progressive MS, then disease progression is suppressed, but severe side effects and controversy arise

Engineering Contradiction:

Improvesuppression of disease progressionVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention uses a natural, endogenous protein (alpha B-crystallin) that is already present in the body at low levels in certain tissues. By administering this native chaperone protein or its encoding nucleic acids, the therapy replicates and enhances a naturally occurring protective mechanism rather than introducing foreign immunosuppressants, thereby achieving disease suppression with reduced side effects

Inventive Principle:

Principle #26Copying

Solution Approach 2:

Alpha B-crystallin enables the body's own cells to protect themselves through enhanced chaperone activity. The protein promotes cellular self-protection against stress and protein misfolding, allowing the body to fight disease progression through its own intrinsic mechanisms rather than relying on external immunosuppressants with severe side effects

Inventive Principle:

Principle #25Self-service

Data Source

PatentUS8835391B2Alpha B-crystallin as a therapy for multiple sclerosis

Publication Date: 2014.09.16 THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV

AI summary

The invention provides methods for treating inflammatory diseases by administering to the subject an effective amount of an agent that provides alpha B-crystallin activity, where the dose is effective to suppress or prevent initiation, progression, or relapses of disease, including the progression of established disease. In some embodiments, the methods of the invention comprise administering to a subject having a pre-existing inflammatory disease condition, an effective amount of alpha B-crystallin protein, to suppress or prevent relapses of the disease.