BMP Biomarkers for LRRK2 Inhibitor Selection in Parkinson's

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Solution Overview

Problem

Current treatments for Parkinson's disease associated with wild-type LRRK2 are inadequate as there is no way to identify patients who would benefit from LRRK2 inhibitor therapy due to the risk of harm to those without pathological LRRK2 activity.

Innovation Solution

Using biomarkers such as bis(monoacylglycero) phosphate (BMP) and/or hemi-bis(monoacylglycero) phosphate (hemi-BMP) levels to determine if LRRK2 inhibitor therapy would be effective for treating Parkinson's disease, by measuring these biomarkers in biofluids like urine or cerebrospinal fluid.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If LRRK2 inhibitors are given to PD patients indiscriminately, then more patients may potentially benefit from the therapy, but patients without pathological LRRK2 activity may be harmed

Engineering Contradiction:

Improvetreatment coverageVSAvoidharm to patients without pathological LRRK2 activity

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces BMP and hemi-BMP biomarkers as intermediaries to identify patients with pathological LRRK2 activity. These biomarkers serve as a mediator between the patient population and LRRK2 inhibitor therapy, enabling safe and effective patient selection without requiring direct measurement of LRRK2 activity.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If current treatments (levodopa, dopamine agonists, monoamine oxidase inhibitors) are used for PD, then motor impairment symptoms can be alleviated, but effectiveness is lost as disease progresses and side effects outweigh benefits

Engineering Contradiction:

Improvesymptom alleviationVSAvoidduration of treatment effectiveness

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent changes the therapeutic parameter from symptomatic management (dopamine replacement) to disease-modifying treatment (LRRK2 inhibition). By targeting the underlying pathological mechanism in a subset of patients, the treatment aims to provide longer-lasting benefits and potentially alter disease progression rather than merely managing symptoms.

Inventive Principle:

Principle #35Parameter changes

3Ease of operation

If no biomarkers are used for patient selection, then all PD patients can be treated uniformly, but the subset of patients who would benefit from LRRK2 inhibitors cannot be identified

Engineering Contradiction:

Improvetreatment simplicityVSAvoidinformation about patient responsiveness to LRRK2 inhibitors

Core Design Contradiction:

Ease of operationVSLoss of information

Solution Approach 1:

The patent replaces the need for direct LRRK2 activity measurement (complex mechanical/biological assay) with biomarker measurement (chemical analysis of BMP and hemi-BMP levels). This substitution maintains ease of operation by using routine biochemical tests while providing the necessary information to identify responsive patients.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Data Source

PatentUS20260011407A1Predictive biomarkers and use thereof to treat parkinson's disease

Publication Date: 2026.01.08 NEURON23 INC

AI summary

The invention provides methods of treating patients with Parkinson's disease (PD) associated with wild-type LRRK2. The invention recognizes that analysis of biomarkers in such patients allows identification of those patients who will respond to LRRK2 inhibitors. Thus, the invention provides methods of identifying PD patients who will respond to LRRK2 inhibitors and methods of treating such patients.