HGF and iPS Cell Therapy for Severe Spinal Cord Injury Recovery

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Solution Overview

Problem

Current therapeutic methods are inadequate for treating severe spinal cord injuries, particularly during the acute and subacute phases, and hepatocyte growth factor (HGF) or induced pluripotent stem cells (iPS) alone do not provide sufficient effects, such as enabling load walking.

Innovation Solution

A combination therapeutic agent comprising a hepatocyte growth factor protein or a substance with comparable c-Met phosphorylation action, and iPS cell-derived neural stem cells or neural progenitor cells, administered intrathecally to the lesion site of the spinal cord, promoting regeneration, inhibiting atrophy and demyelination, and enhancing axon elongation and remyelination.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If HGF or iPS cells alone are administered to treat severe spinal cord injury, then some neurotrophic effect is achieved, but sufficient functional recovery (e.g., load walking) is not obtained

Engineering Contradiction:

Improvetherapeutic effectVSAvoidfunctional recovery

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent combines HGF (hepatocyte growth factor) and iPS cells (induced pluripotent stem cells) into a single therapeutic agent administered together for spinal cord injury treatment. This merging of two separate therapeutic components creates a synergistic effect that overcomes the limitations of using either component alone, achieving both reliable neuroprotection and sufficient functional recovery including load walking capability.

Inventive Principle:

Principle #5Merging (Combining)

2Ease of manufacture

If conventional therapeutic methods are used for severe spinal cord injury, then treatment is provided, but effective therapeutic methods are not established

Engineering Contradiction:

Improvetreatment availabilityVSAvoidtherapeutic efficacy

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The patent creates a composite therapeutic agent combining HGF (a protein factor) and iPS cells (living cells) into a unified treatment formulation. This composite approach integrates molecular therapy and cellular therapy, providing both immediate neurotrophic support and long-term regenerative capacity, thereby establishing an effective therapeutic method for severe spinal cord injury that was not achievable with conventional single-modality treatments.

Inventive Principle:

Principle #40Composite materials

3Stability of the object's composition

If the central nervous system is considered non-regenerative after injury, then no regeneration is expected, but the combination therapy promotes regeneration from acute to subacute phase

Engineering Contradiction:

Improvetissue integrityVSAvoidregenerative capacity

Core Design Contradiction:

Stability of the object's compositionVSAdaptability or versatility

Solution Approach 1:

The patent administers the combination of HGF and iPS cells during the acute to subacute phase transition period, creating favorable conditions before complete scar formation occurs. HGF provides immediate neuroprotection and reduces secondary injury, while iPS cells are introduced at a time when they can effectively differentiate and integrate into the injured circuitry, thereby promoting regeneration before the tissue becomes permanently fixed in its damaged state.

Inventive Principle:

Principle #10Preliminary action

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 combination agent alleviates motor dysfunction, inhibits spinal cord cavitation, enhances axon elongation and remyelination, and improves functional nerve fiber density, facilitating recovery of lower limb motor function and walking ability.

Implementation Method 1

the HGF protein acts on the c-Met receptors of many cells, such as an epithelial cell and a vascular endothelial cell, as well as a hepatocyte, to be involved in the damage repair and regeneration of tissues and organs

Methodology Applied

Scientific EffectReceptor-mediated signaling:

Implementation Method 2

a pluripotent stem cell... an iPS cell-derived neural stem cell and/or neural progenitor cells

Methodology Applied

Scientific EffectCell differentiation:

Implementation Method 3

a promoter for migration/axon elongation in a lesion site of a spinal cord

Methodology Applied

Scientific EffectCell migration:

Data Source

PatentUS20250381247A1Spinal cord injury therapeutic targeting from acute phase to subacute phase

Publication Date: 2025.12.18 KRINGLE PHARMA INC

AI summary

Provided is a therapeutic agent for spinal cord injury from an acute phase to a subacute phase that has heretofore been difficult to treat, in particular, severe spinal cord injury. The therapeutic agent for spinal cord injury from an acute phase to a subacute phase includes the following: (1) (a) a hepatocyte growth factor protein or a substance having a c-Met phosphorylation action comparable to that of the hepatocyte growth factor protein, or (b) a gene encoding the hepatocyte growth factor protein or a gene encoding the substance having a c-Met phosphorylation action comparable to that of the hepatocyte growth factor protein; and (2) a pluripotent stem cell.