Chemical Reprogramming of Glial Cells into Neurons
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Solution Overview
Problem
Current therapies for brain disorders such as stroke and Alzheimer's disease lack effective methods for reversing progression due to insufficient neuron regeneration, with cell transplantation facing hurdles like immunorejection, tumorigenesis, and differentiation uncertainty, and existing chemical conversions requiring external cells or viral vectors.
Innovation Solution
The use of FDA-approved compounds like Ceritinib, Pirfenidone, Crizotinib, Flurbiprofen, Lithium Chloride, and Vitamin C to chemically reprogram glial cells into functional neurons in situ, avoiding the need for external cell transplantation and viral vectors, and allowing for in vivo conversion within the nervous system.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If cell transplantation therapy is used to regenerate neurons, then neuron replacement is achieved, but immunorejection and tumorigenesis occur
Solution Approach 1:
The patent enables the body's own glial cells to convert into neurons through chemical reprogramming, eliminating the need for external cell transplantation. This self-service approach avoids immunorejection and tumorigenesis while achieving neuron regeneration in situ within the nervous system
Solution Approach 2:
The patent uses a small molecule cocktail as an intermediary to mediate the conversion of glial cells into neurons. This chemical mediator triggers endogenous cell fate changes without requiring external cell introduction, thereby avoiding the harmful effects associated with transplantation
2Ease of operation
If viral vectors are used to express transcription factors for cell conversion, then in vivo conversion is achieved, but safety risks from exogenous genes increase
Solution Approach 1:
The patent replaces the mechanical/biological system of viral vector delivery with a chemical system using small molecules. This substitution eliminates the safety risks associated with exogenous genes and viral integration while maintaining the ability to achieve in vivo cell conversion through pharmacological agents
Solution Approach 2:
The patent uses small molecule compounds that can be administered and cleared from the body, replacing persistent viral vectors. These chemical agents provide temporary but sufficient activity to trigger cell conversion without long-term genomic integration risks
3Quantity of substance
If stem cells are manipulated in culture to differentiate into neurons, then neuron production is achieved, but complex manipulation and transplantation requirements increase
Solution Approach 1:
The patent enables glial cells to autonomously convert into neurons through chemical reprogramming within their native tissue environment. This eliminates the need for complex ex vivo manipulation, culture, and transplantation procedures, significantly simplifying the overall process while maintaining neuron production
Solution Approach 2:
The patent breaks down the complex process of neuron generation into a simple chemical treatment step applied directly in vivo. Instead of multi-step procedures involving cell isolation, culture, differentiation, and transplantation, the solution segments the problem into a single pharmacological intervention that achieves the same outcome
Data Source
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AI summary
Provided are compositions, articles and methods that relate to promoting neurogenesis or neuroregeneration in mammalian nervous system. Embodiments relate to use of groups of compounds that contain Crizotinib (Cri), Flurbiprofen, Lithium Chloride (Li), Vitamin C (VC), Ceritinib (Cer) or Pirfenidone (PFD). In certain implementations glial cells are converted into functional neurons for the treatment of Huntington's disease.