Intranasal NGF Delivery for Niemann-Pick C CNS Cholesterol Control

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Solution Overview

Problem

Current therapies for Niemann-Pick type C disease, such as Miglustat, HP-β-CD, and Vorinostat, are associated with adverse effects and limited efficacy due to their inability to effectively cross the blood-brain barrier, leading to suboptimal treatment outcomes.

Innovation Solution

Administration of nerve growth factor (NGF) and brain-derived nerve factor (BDNF) intranasally to reduce cholesterol buildup and restore normal cholesterol homeostasis in NPC cells, promoting the correct localization of NPC1 protein and reducing abnormal lipid accumulation in the CNS.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current therapies (Miglustat, HP-β-CD, Vorinostat) are administered to treat NPC disease, then cholesterol accumulation is reduced to some extent, but the treatments cannot effectively cross the blood-brain barrier, resulting in limited efficacy in the CNS

Engineering Contradiction:

Improvetreatment efficacyVSAvoidinability to cross blood-brain barrier

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent employs intranasal administration as an intermediary route that bypasses the blood-brain barrier. The nasal cavity provides direct access to the CNS through the olfactory nerve pathway, allowing therapeutic agents to reach brain tissue without needing to cross the restrictive blood-brain barrier that blocks conventional systemic administration routes.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the conventional systemic circulation route (which requires crossing the blood-brain barrier) with a direct nasal-to-brain delivery mechanism. This substitution utilizes the anatomical and physiological properties of the nasal mucosa and olfactory pathway to achieve direct CNS access, eliminating the barrier problem entirely rather than trying to overcome it.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Reliability

If current therapies are used to reduce cholesterol accumulation, then some lipid reduction is achieved, but adverse effects occur that outweigh the potential benefits

Engineering Contradiction:

Improvecholesterol reduction efficacyVSAvoidadverse effects

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent changes the delivery parameters (administration route from systemic to intranasal) and dosing parameters (frequency and amount) to achieve therapeutic效果的同时减少副作用。通过优化这些参数，在有效降低胆固醇积累的同时，显著减少了当前疗法的有害作用。

Inventive Principle:

Principle #35Parameter changes

3Reliability

If NGF or BDNF is administered intranasally to reduce sterol accumulation in CNS, then cholesterol buildup decreases and NPC1 protein localization improves, but the treatment requires frequent administration

Engineering Contradiction:

Improvesterol accumulation reductionVSAvoidtreatment duration frequency

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent implements periodic administration (e.g., daily or every other day) of NGF or BDNF via intranasal route. This periodic dosing schedule maintains therapeutic levels of the growth factors in the CNS, ensuring continuous reduction of sterol accumulation and sustained improvement of NPC1 protein localization, while balancing the need for frequent administration with patient compliance.

Inventive Principle:

Principle #19Periodic action

Data Source

PatentEP4659759A1Administration of NGF for the treatment of niemann-pick type c disease

Publication Date: 2025.12.10 DOMPE FARMACEUTICI SPA

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AI summary

The present invention relates to Nerve growth factor (NGF) or a mutein thereof, for use in the treatment of Niemann-Pick type C in a subject.