IGF-1R Antisense Oligonucleotide for Thyroid Eye Disease
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Solution Overview
Problem
Current treatments for medium and severe thyroid-associated ophthalmopathy (TAO) are inadequate, with glucocorticoids and radiotherapy causing systemic side effects, and there is a lack of effective antisense oligonucleotides targeting the insulin-like growth factor 1 receptor (IGF-1R) for therapeutic use.
Innovation Solution
Development of a thioantisense oligonucleotide (S-ASODN-1) with a specific sequence targeting the IGF-1R gene to reduce IGF-1R and anti-thyroid peroxidase antibody (TPO-Ab) concentrations, formulated as a lyophilized agent or injection, potentially combined with other treatments.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If glucocorticoids and radiotherapy are used to treat medium and severe TAO, then inflammatory response is suppressed, but systemic side effects occur
Solution Approach 1:
The patent extracts the therapeutic action from systemic administration and localizes it to the orbital tissue site. By using locally administered antisense oligonucleotides, the treatment achieves anti-inflammatory effects specifically at the target site without distributing the drug systemically, thereby eliminating systemic side effects while maintaining efficacy in suppressing inflammatory response in TAO patients
Solution Approach 2:
The patent employs antisense oligonucleotides as molecular intermediaries that specifically bind to IGF-1R mRNA to inhibit its translation. This intermediary mechanism allows precise targeting of the IGF-1R pathway in orbital tissues without activating systemic immune responses or causing the systemic side effects associated with traditional glucocorticoid and radiotherapy treatments
2Reliability
If conventional treatments are used for TAO, then some therapeutic effect is achieved, but treatment effectiveness is insufficient for medium and severe cases
Solution Approach 1:
The patent changes the fundamental parameter of treatment delivery from systemic to local administration. By administering antisense oligonucleotides directly to orbital tissues, the treatment achieves high local concentration and efficacy for medium and severe TAO cases, while the modular nature of the therapy allows adaptation to different disease severities and patient conditions
3Object-affected harmful factors
If IGF-1R is targeted to reduce orbital tissue expansion, then proptosis is improved, but specific therapeutic agents were previously unavailable
Solution Approach 1:
The patent replaces the unavailable mechanical/biological therapeutic agents with chemically synthesized antisense oligonucleotides. These synthetic molecules can be manufactured through chemical synthesis methods, providing a readily available and scalable treatment that targets IGF-1R to reduce orbital tissue expansion and improve proptosis in TAO patients
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
S-ASODN-1 effectively regulates TPO-Ab and thyroid-stimulating hormone (TSH) levels, reducing orbital tissue expansion and inflammation, providing a non-systemic treatment for TAO.
Implementation Method 1
an antisense oligonucleotide S-ASODN-1 with a particular sequence targeting an IGF-1R can effectively reduce concentrations of the IGF-1R and an anti-thyroid peroxidase antibody (TPO-Ab)
Data Source
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AI summary
The present disclosure relates to the field of gene therapies of thyroid-associated ophthalmopathy (TAO) and, in particular, to a use of an antisense oligonucleotide in preparation of a drug for treating a disease caused by an abnormal thyroid. Experimental results of the present application indicate that an antisense oligonucleotide S-ASODN-1 with a particular sequence targeting an insulin-like growth factor 1 receptor (IGF-1R) can effectively reduce concentrations of the IGF-1R and an anti-thyroid peroxidase antibody (TPO-Ab), thereby improving a level of thyroid-stimulating hormone (TSH) for treating thyroid-associated ophthalmopathy.