Imatinib Dosage Regime for Stroke Treatment
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Solution Overview
Problem
Current treatments for acute ischemic stroke, such as thrombolytic therapy with tPA, have limited therapeutic windows and are associated with severe side effects, and there is a need for improved treatments that can be administered before definitive diagnosis, especially in cases where delays in diagnosis or equipment availability hinder timely intervention.
Innovation Solution
Administering Imatinib, a tyrosine kinase inhibitor, at a dose of 650 mg/day or higher for at least 3 consecutive days, either before, during, or after thrombectomy or thrombolysis, potentially extending the therapeutic window for thrombolysis and improving outcomes regardless of the stroke type.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If thrombolytic therapy with tPA is administered to dissolve clots and improve blood flow, then the effectiveness of stroke treatment is improved, but severe side effects such as neurotoxicity and increased vascular permeability occur
Solution Approach 1:
Imatinib acts as an intermediary substance that modifies the biological environment to reduce the harmful effects of tPA. By inhibiting PDGF receptors and reducing inflammatory responses, Imatinib mediates between the thrombolytic action of tPA and the protection of brain tissue, allowing effective clot dissolution while minimizing neurotoxicity and vascular permeability changes
Solution Approach 2:
The patent converts the potentially harmful inflammatory and proliferative responses triggered by tPA into beneficial protective effects. By using Imatinib to modulate these responses, the harmful side effects are transformed into a controlled biological environment that supports safe and effective thrombolytic therapy
2Measurement precision
If tPA therapy is delayed beyond the recommended therapeutic window to allow for proper diagnosis, then diagnostic accuracy is improved, but the effectiveness of thrombolytic treatment decreases
Solution Approach 1:
Imatinib is administered as a preliminary action before tPA therapy to prepare the biological environment for safe thrombolytic treatment. This preliminary administration allows clinicians to proceed with tPA therapy without waiting for complete diagnostic confirmation, as Imatinib already provides protection against potential side effects
Solution Approach 2:
Imatinib provides preliminary anti-action by pre-inhibiting the pathways that would lead to harmful side effects of tPA. This preliminary protection allows for earlier administration of tPA therapy, effectively counteracting the time-dependent loss of treatment effectiveness
3Loss of time
If the therapeutic window for thrombolysis is extended to allow later administration, then more patients can receive treatment, but the severity of side effects increases
Solution Approach 1:
The patent changes the biological parameters of the patient's system by administering Imatinib, which modifies the response to tPA even when given later. This parameter change allows extension of the therapeutic window while maintaining acceptable side effect profiles, as Imatinib alters the biological environment to be more tolerant of delayed therapy
Data Source
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AI summary
Imatinib can be used in the treatment of stroke in a new dosage regime, where Imatinib is administered to the patient at a dose of 650 mg/day or higher for at least 3 consecutive days, and preferably administered in a starting dose of 1000 mg/day or higher on day 1, and ata dose in the interval of 650 mg/day to 1000 mg/day on the subsequent days. A method for the treatment of stroke, a pharmaceutical composition and a kit of parts is/are also disclosed.