Oral ATM Inhibitor AZD1390 for Spinal Cord Injury
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Solution Overview
Problem
Current treatments for spinal cord injury (SCI) are limited, with no cure available and existing drugs only providing palliative relief for neuropathic pain, while facing challenges such as low neuronal regrowth capacity and inhibitory molecules in the CNS environment, necessitating the development of effective therapeutic agents that can cross the blood-brain barrier to address neuronal damage and degeneration.
Innovation Solution
The use of brain-penetrant ATM inhibitors like AZD1390, which can be administered orally to inhibit ATM function, promoting neuronal survival and regeneration without direct CNS administration, thereby facilitating functional recovery in SCI and potentially other neurological conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If ATM inhibitors are administered directly into the CNS (e.g., via intrathecal injection), then effective concentration is achieved for neuronal protection, but treatment complexity and invasiveness increase
Solution Approach 1:
The patent uses the bloodstream as an intermediary medium to deliver the ATM inhibitor (AZD1390) to the CNS. Instead of direct CNS injection, the drug is administered orally and transported through the blood circulation system, crossing the blood-brain barrier to reach the spinal cord and brain tissues where it exerts its protective effect on neurons.
2Reliability
If conventional ATM inhibitors are used, then ATM function is inhibited, but the drugs cannot cross the blood-brain barrier effectively
Solution Approach 1:
The patent employs AZD1390, which has modified chemical and pharmacokinetic parameters compared to conventional ATM inhibitors. Specifically, AZD1390 possesses enhanced lipophilicity and molecular properties that enable it to cross the blood-brain barrier effectively, while maintaining its ATM inhibitory activity. This parameter optimization allows the drug to reach therapeutic concentrations in the CNS after oral administration.
Data Source
AI summary
The present disclosure relates to the use of ATM inhibitors, such as AZ1390 and related compounds, in the treatment of various neurological conditions, by protecting against or treating neuronal damage or neuronal degeneration, including traumatic injury, such as spinal cord injury (SCI).