Dye-Bound Cyclized Peptides for CNS-Penetrant TrkB/TrkC Modulation
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Solution Overview
Problem
Current treatments for spinal cord injuries (SCI) and Alzheimer's disease (AD) are inadequate in promoting functional locomotor recovery and cognitive improvement, with existing FDA-approved drugs having limited efficacy and adverse effects, while TrkB/TrkC modulators face challenges due to poor pharmacokinetic profiles and lack of CNS permeability.
Innovation Solution
Development of dye-bound cyclized peptides, such as 5c(i), which modulate TrkB and TrkC receptors, enhancing neurite regeneration, axon regeneration, and neuronal survival, and potentially improving secondary pathologies like liver fibrosis and heart atrophy, while also serving as diagnostic and therapeutic agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If TrkB/TrkC modulators are used to promote neurological recovery, then neuronal survival and axon regeneration are improved, but pharmacokinetic profiles are poor and CNS permeability is lacking
Solution Approach 1:
The patent modifies the chemical parameters of TrkB/TrkC modulators by conjugating them to fluorescent dyes and cyclizing their structures. This parameter change transforms the pharmacokinetic properties while maintaining or enhancing their ability to promote neuronal survival and axon regeneration, directly resolving the contradiction between efficacy and pharmacokinetic complexity
Solution Approach 2:
The invention creates composite therapeutic agents by combining TrkB/TrkC modulator molecules with fluorescent dye molecules. This composite structure integrates the neurological recovery-promoting activity of the modulator with the imaging capabilities of the dye, while the cyclized peptide structure provides improved pharmacokinetic stability, thus resolving the contradiction between efficacy and pharmacokinetic profile complexity
2Object-affected harmful factors
If FDA-approved drugs like methylprednisolone are used to treat SCI, then secondary inflammatory pathologies are mitigated, but locomotor recovery is not improved and adverse effects occur
Solution Approach 1:
The patent extracts and isolates the specific TrkB/TrkC receptor-targeting activity from complex FDA-approved drug formulations. By focusing on this single mechanism of action and optimizing it through cyclized peptide-conjugate design, the invention achieves improved locomotor recovery without the adverse effects associated with broad-spectrum anti-inflammatory drugs like methylprednisolone
Solution Approach 2:
The cyclized peptide-conjugate acts as an intermediary molecule that specifically mediates the interaction between TrkB/TrkC receptors and their ligands. This intermediary approach provides targeted neurological recovery promotion without triggering the systemic adverse effects of conventional anti-inflammatory medications, resolving the contradiction between inflammation mitigation and locomotor recovery
3Reliability
If early diagnosis and treatment are implemented, then neurological recovery is improved, but many patients are not diagnosed early enough
Solution Approach 1:
The patent creates a multi-functional therapeutic agent that simultaneously provides treatment and diagnostic capabilities. The fluorescent dye component enables real-time imaging and tracking of the therapeutic agent's distribution and efficacy, while the TrkB/TrkC modulator component provides neurological recovery promotion. This dual functionality eliminates the need for separate diagnostic procedures and enables immediate treatment initiation upon administration
Solution Approach 2:
The fluorescent dye-conjugated TrkB/TrkC modulator provides real-time feedback through fluorescence imaging, allowing clinicians to monitor the distribution, uptake, and efficacy of the therapeutic agent in vivo. This feedback mechanism enables immediate assessment of treatment response and facilitates timely adjustments to therapy, directly addressing the diagnosis delay problem by providing instant diagnostic information
Data Source
AI summary
Embodiments of the disclosure include methods and compositions related to use of compound comprising a particular peptide linked to a dye. In specific embodiments, the peptide DIRG is linked to the BODIPY dye. In specific embodiments, the compositions are utilized for treatment of neurological conditions and secondary pathologies related therewith, such as spinal cord injury and Alzheimer's Disease, as examples.