Dazucorilant GR Modulation for Slowing ALS Progression
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Solution Overview
Problem
Current treatments for amyotrophic lateral sclerosis (ALS) are palliative and do not effectively slow disease progression, leading to a devastating and ultimately fatal outcome with a survival time of about 3 to 5 years after onset.
Innovation Solution
Administering a heteroaryl ketone fused azadecalin compound, such as dazucorilant, which modulates glucocorticoid receptors (GRs) to treat ALS, either alone or in combination with other ALS treatments like riluzole or edaravone, to potentially slow disease progression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current ALS treatments (riluzole, edaravone) are administered, then palliative care is provided, but disease progression is not effectively slowed and survival time remains limited to 3-5 years
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of glucocorticoid compounds to create novel heteroaryl ketone fused azadecalin compounds with optimized pharmacological properties. These structural modifications aim to enhance therapeutic efficacy and potentially alter the disease progression trajectory, moving beyond the limited survival extension provided by current treatments
Solution Approach 2:
The patent uses glucocorticoid receptor modulation as an intermediary mechanism to address ALS pathology. By targeting the glucocorticoid receptor pathway with novel compounds, the invention seeks to mediate protective effects against motor neuron degeneration, potentially slowing disease progression through this intermediate biological pathway
2Duration of action of moving object
If novel heteroaryl ketone fused azadecalin compounds are administered, then disease progression may be slowed and survival improved, but treatment complexity and development requirements increase
Solution Approach 1:
The patent employs universality by designing glucocorticoid receptor modulators that may address multiple aspects of ALS pathology simultaneously. The novel compounds aim to provide broad protective effects through a single mechanism of action, potentially simplifying the overall treatment approach despite the complexity of the molecular structure
Data Source
AI summary
Applicant discloses methods and compositions for treating a patient suffering from amyotrophic lateral sclerosis (ALS) comprising administration of a heteroaryl ketone fused azadecalin compound. In embodiments, the heteroaryl ketone fused azadecalin compound is dazucorilant: (R)-(1-(4-fluorophenyl)-6-((4-(trifluoromethyl)phenyl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1-H-pyrazolo[3,4-g]isoquinolin-4a-yl)(pyridin-2-yl)methanone, having the chemical structure illustrated asSuitable doses include daily administration of 150 milligrams and 300 milligrams of dazucorilant. Suitable doses include daily administration of dazucorilant with food, or with water, or with food and water. Daily administration of dazucorilant is effective to increase dazucorilant exposure up to about 2-fold when continued for seven days or more. Administration of such a heteroaryl ketone fused azadecalin compound may comprise oral administration, enteral administration, or other administration. Pharmaceutical compositions comprising dazucorilant are useful in the treatment of patients suffering from ALS. Suitable pharmaceutical compositions comprising dazucorilant include, e.g., pharmaceutical compositions for oral administration and pharmaceutical compositions for enteral administration.