Modified Oligonucleotides for Reducing LRRK2 Expression
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Solution Overview
Problem
Current treatments for neurodegenerative diseases like Parkinson's Disease, particularly those mediated by LRRK2, lack effective options for reducing LRRK2 mRNA and protein expression, which contributes to symptoms such as loss of motor function, aggregate formation, and neuron death.
Innovation Solution
Administration of oligomeric compounds, specifically modified oligonucleotides that are complementary to LRRK2 mRNA, to reduce its expression in animals, thereby ameliorating symptoms of Parkinson's Disease, including those not associated with LRRK2 genetic mutations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional treatments are used for Parkinson's Disease, then current therapeutic options are limited, but LRRK2 mRNA and protein expression cannot be reduced
Solution Approach 1:
The patent employs antisense oligonucleotides as intermediary molecules that bind to LRRK2 mRNA to prevent its translation into protein. These oligonucleotide intermediaries specifically target and silence the LRRK2 gene expression, providing a mechanism to reduce LRRK2 protein levels that was previously unavailable through conventional treatments
Solution Approach 2:
The invention changes the therapeutic parameter from symptomatic management to targeting gene expression levels. By using modified oligonucleotides that alter mRNA stability and translation efficiency, the treatment directly modifies the biochemical parameters of LRRK2 expression, enabling reduction of both mRNA and protein levels
2Productivity
If LRRK2 expression is not reduced, then current treatments provide limited options, but no effective therapy exists for neurodegenerative symptoms
Solution Approach 1:
The patent applies preliminary action by targeting LRRK2 mRNA expression before neurodegenerative damage occurs or progresses. The antisense oligonucleotides prevent LRRK2 protein synthesis in advance, thereby preventing the harmful effects of elevated LRRK2 levels before they cause neuronal damage, aggregate formation, or motor function loss
3Quantity of substance
If modified oligonucleotides are administered, then LRRK2 mRNA and protein levels decrease, but this requires a new treatment approach
Solution Approach 1:
The patent replaces conventional pharmacological mechanisms with a nucleic acid-based mechanism. Instead of using small molecule drugs that attempt to inhibit LRRK2 kinase activity, the invention uses antisense oligonucleotides that directly bind to LRRK2 mRNA through complementary base pairing, substituting a chemical inhibition approach with a molecular recognition and silencing approach
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 use of modified oligonucleotides effectively decreases LRRK2 mRNA and protein levels, leading to improved motor function, reduced aggregate formation, and preservation of neurons, providing therapeutic benefits for Parkinson's Disease symptoms.
Implementation Method 1
modified oligonucleotides that are complementary to LRRK2 mRNA
Data Source
AI summary
Provided herein are methods for decreasing LRRK2 mRNA expression. Such methods are useful to ameliorate LRRK2 associated diseases. Such LRRK2 associated diseases include Parkinson's Disease, including non-LRRK2 mediated Parkinson's Disease.