Oligonucleotides Modulate TMEM106B Expression
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Solution Overview
Problem
Current treatments for neurodegenerative disorders lack effective inhibitors for Transmembrane protein 106B (TMEM106B), which is associated with various neurodegenerative diseases, including frontotemporal lobar degeneration, Parkinson's disease, and amyotrophic lateral sclerosis, highlighting a need for specific inhibitors to modulate TMEM106B expression.
Innovation Solution
Development of oligonucleotides that are complementary to TMEM106B, such as antisense oligonucleotides and siRNAs, to down-regulate its expression, which can be used therapeutically to treat neurodegenerative disorders by administering them in vivo or in vitro.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If TMEM106B expression is increased to improve lysosomal functioning and dendrite morphogenesis, then cellular functions are enhanced, but neurodegenerative disease risk increases
Solution Approach 1:
The patent applies parameter changes by modulating TMEM106B expression levels to optimal ranges. Through oligonucleotide-based gene expression modulation, the invention adjusts TMEM106B protein levels to maintain lysosomal functioning and dendrite morphogenesis while preventing excessive expression that would increase neurodegenerative disease risk. This involves precise control of expression parameters to achieve therapeutic benefit without harm.
2Object-affected harmful factors
If TMEM106B expression is decreased to reduce neurodegenerative disease risk, then disease susceptibility is reduced, but lysosomal functioning and dendrite morphogenesis are impaired
Solution Approach 1:
The invention uses parameter changes to precisely control TMEM106B expression levels. By employing oligonucleotides that modulate gene expression, the patent achieves optimal TMEM106B protein levels that maintain lysosomal functioning and dendrite morphogenesis while reducing neurodegenerative disease risk. The parameter modulation ensures expression is reduced from pathological levels without falling below functional thresholds.
3Reliability
If specific oligonucleotides are developed to modulate TMEM106B expression, then therapeutic effectiveness is improved, but development complexity and cost increase
Solution Approach 1:
The patent applies universality by developing oligonucleotide platforms that can modulate TMEM106B expression across multiple neurodegenerative disease contexts. The same oligonucleotide technology platform can be adapted for different indications including frontotemporal lobar degeneration, Parkinson's disease, and amyotrophic lateral sclerosis, reducing overall development complexity through multi-purpose application.
Solution Approach 2:
The invention uses oligonucleotides as intermediary molecules to modulate TMEM106B expression. These oligonucleotides serve as mediators between therapeutic intervention and the target protein, enabling precise control of gene expression. The oligonucleotide intermediaries can be delivered via various vectors and mechanisms, providing flexibility in overcoming delivery challenges while maintaining therapeutic effectiveness.
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 oligonucleotides effectively decrease TMEM106B expression, providing a potential therapeutic approach for neurodegenerative diseases like frontotemporal lobar degeneration, Parkinson's disease, and other related conditions by modulating gene expression at the cellular level.
Implementation Method 1
The invention provides for an oligonucleotide targeting TMEM106B, which comprises a contiguous nucleotide sequence of 10-30 nucleotides in length with at least 90% complementary, such as fully complementary, to a mammalian TMEM106B target nucleic acid
Data Source
AI summary
The present invention relates to oligonucleotides that are complementary to and modulate the expression of TMEM106B. The present invention further relates to conjugates of the oligonucleotide and pharmaceutical compositions and methods for treatment of neurological disorders using the oligonucleotide.