Auditory Cell Calcium Flux Modulation for Hearing Loss Prevention

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Hearing loss is caused by the over-activation of the unfolded protein response (UPR) due to dysregulated calcium fluxes, leading to apoptosis of auditory cells such as hair cells, with significant prevalence and societal costs.

Innovation Solution

Treatments that inhibit or reverse abnormal calcium fluxes and modulate maladaptive UPR pathways in auditory cells, including the use of agents that enhance or stabilize SERCA2b activity, calcium pumps, and UPR signaling molecules to prevent cell death and promote adaptive responses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If the unfolded protein response is over-activated due to dysregulated calcium fluxes, then auditory cell death is promoted, but hearing function is lost

Engineering Contradiction:

Improveauditory cell survivalVSAvoidUPR over-activation

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces calcium flux modulators and UPR pathway inhibitors as intermediary substances that intervene between the harmful calcium fluxes and the auditory cells. These modulators act as mediators to regulate calcium homeostasis and prevent UPR over-activation, thereby protecting hair cells from apoptosis while allowing normal hearing function to be maintained.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent applies parameter changes by modulating calcium flux dynamics and UPR pathway activity. Through pharmacological agents that alter calcium homeostasis parameters and UPR signaling intensity, the invention shifts the system from a harmful state of UPR over-activation to a balanced state that promotes cell survival and prevents hearing loss.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If calcium fluxes are dysregulated, then apoptotic UPR processes are over-activated, but auditory cell death occurs

Engineering Contradiction:

Improvehair cell survivalVSAvoidapoptotic UPR processes

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent converts the harmful effect of dysregulated calcium fluxes into a beneficial outcome by using calcium modulators to restore proper calcium homeostasis. The same calcium signaling pathways that cause UPR over-activation and apoptosis are redirected to promote adaptive UPR responses and cell survival, transforming the harmful calcium fluxes into protective mechanisms.

Inventive Principle:

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

Solution Approach 2:

UPR pathway inhibitors and calcium flux modulators serve as intermediary agents that specifically target and inhibit the harmful apoptotic UPR processes while preserving beneficial UPR functions. These intermediaries block the pro-apoptotic signaling cascade initiated by dysregulated calcium fluxes, thereby preventing hair cell death.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If maladaptive UPR pathways are active, then hearing loss progresses, but adaptive responses are suppressed

Engineering Contradiction:

Improvehearing function preservationVSAvoidUPR response adaptability

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent implements feedback mechanisms through UPR pathway modulators that sense and respond to the state of UPR activation. These agents provide feedback control to distinguish between adaptive and maladaptive UPR responses, enhancing adaptive pathways that promote cell survival while suppressing maladaptive pathways that lead to apoptosis, thereby preserving hearing function.

Inventive Principle:

Principle #23Feedback

Solution Approach 2:

The invention changes the parameters of UPR pathway activity to shift the balance between adaptive and maladaptive responses. By modulating UPR signaling intensity and duration through pharmacological agents, the system transitions from a state of maladaptive UPR over-activation to a state of balanced, adaptive UPR responses that protect against hearing loss.

Inventive Principle:

Principle #35Parameter changes

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

The treatments effectively reduce or reverse hearing loss severity, protect against future damage, and preserve auditory cell function, offering therapeutic and preventative benefits for various forms of hearing impairment.

Implementation Method 1

enhance or stabilize SERCA2b activity, calcium pumps

Methodology Applied

Scientific EffectCalcium pump (SERCA2b):

Implementation Method 2

the death of hair cells in the ear can be caused by over-activation of the unfolded protein response

Methodology Applied

Scientific EffectUnfolded protein response (UPR):

Implementation Method 3

the action of dysregulated calcium fluxes has been implicated in the death of hair cells

Methodology Applied

Scientific EffectCalcium flux:

Data Source

PatentEP3368037B1Novel methods of treating hearing loss

Publication Date: 2026.04.08 RGT UNIV OF CALIFORNIA

Figure 1~2
Figure 3~5
Figure 6~7

AI summary

Provided are methods of treating various forms of hearing loss caused by aberrant calcium fluxes in auditory cells. The methods encompass the administration of agents which prevent abnormal calcium fluxes, stabilize SERCA2b activity, or prevent ER UPR apoptotic responses. The methods include therapeutic treatments of subjects suffering from hearing loss as well as preventative treatments which protect auditory cells from cell death, for example as caused by exposure to loud noise.