PDE1A PDE1C Modulators for Synucleinopathy Treatment
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Solution Overview
Problem
Current therapies are ineffective in slowing or halting the progression of synucleinopathies, which are characterized by abnormal deposition of alpha-synuclein, leading to neurodegenerative diseases such as multiple system atrophy, dementia with Lewy bodies, and Parkinson's disease, with no available treatments to address the underlying toxicity and neuronal damage.
Innovation Solution
The development of modulators, specifically inhibitors, for phosphodiesterase 1A (PDE1A) and 1C (PDE1C) enzymes, such as vinpocetine, which reduce the activity or expression of these enzymes to counteract abnormal alpha-synuclein deposition, thereby preventing or treating synucleinopathies by protecting dopaminergic neurons from toxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies are used for synucleinopathies, then treatment is provided, but the progression of the disease is not slowed or halted
Solution Approach 1:
The patent changes the therapeutic parameter from general symptomatic treatment to specific PDE1A/PDE1C enzyme inhibition, targeting the underlying pathophysiology of synucleinopathies. By modulating phosphodiesterase activity, the invention addresses the root cause of abnormal alpha-synuclein deposition rather than merely managing symptoms, thereby potentially halting disease progression while maintaining treatment effectiveness.
2Reliability
If PDE1A and PDE1C modulators are used, then abnormal alpha-synuclein deposition is reduced, but specificity for these isoforms must be ensured to minimize side effects
Solution Approach 1:
The patent applies local quality by designing compounds with specific molecular characteristics that confer selective affinity for PDE1A and PDE1C isoforms. The chemical structures are engineered to interact preferentially with the unique active site features of these specific phosphodiesterase isoforms, thereby achieving targeted inhibition that reduces abnormal alpha-synuclein deposition while minimizing off-target effects on other PDE isoforms and reducing side effects.
Data Source
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AI summary
The present invention relates to a modulator of PDE1A and/or PDE1C for use as a medicament, in particular for use in the prevention or treatment of synucleinopathies, such multiple system atrophy, dementia with Lewy bodies, Parkinson's disease, pure autonomic failure, rapid eye movement sleep behavior disorder or inherited synucleinopathies caused by mutations or multiplications of the SNCA gene, or synucleinopathies caused by mutations in other genes including, but not limited to GBA, LRRK2 and PARK2.