D-cycloserine intermittent dosing for dementia tolerance
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Solution Overview
Problem
Current treatments for dementia, including Alzheimer's Disease, face challenges due to rapid tolerance development when D-cycloserine (DCS) is administered daily, leading to reduced effectiveness and increased costs, while also posing side effects.
Innovation Solution
Administering DCS or its prodrug on a tolerance-inhibiting basis, where it is given once a day and no more frequently than once a week, to reduce tolerance development and maintain therapeutic benefits, particularly for mild cognitive impairment and other dementia conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If DCS is administered daily for significant periods, then the initial therapeutic benefits are achieved, but tolerance develops rapidly reducing effectiveness
Solution Approach 1:
The patent applies periodic action by administering DCS intermittently rather than continuously. Specifically, it uses dosing schedules such as administering DCS on certain days of the week (e.g., Monday, Wednesday, Friday) or using cycles of treatment followed by drug-free intervals. This periodic administration prevents the continuous exposure that leads to tolerance development, thereby maintaining therapeutic effectiveness over extended periods.
Solution Approach 2:
The patent inverts the conventional approach to chronic daily dosing by deliberately introducing drug-free intervals. Instead of maintaining constant drug presence to ensure effectiveness, the invention uses strategic absence of the drug to prevent tolerance mechanisms from activating, thereby preserving long-term effectiveness through reduced cumulative exposure.
2Reliability
If DCS is administered daily, then initial cognitive benefits are observed, but drug-related costs and side effects increase
Solution Approach 1:
The patent applies partial action by administering DCS at lower frequencies and potentially lower doses compared to continuous daily dosing. By providing sufficient drug exposure during treatment days to achieve cognitive benefits while reducing overall weekly dosage, the invention maintains therapeutic effectiveness while minimizing cumulative side effects and treatment costs.
Solution Approach 2:
Through periodic administration schedules, the patent reduces the total amount of drug administered over time while maintaining peak effectiveness during treatment periods. This approach lowers cumulative exposure-related side effects and reduces overall drug consumption costs while preserving cognitive improvement benefits.
3Reliability
If DCS is administered continuously, then initial memory enhancement is achieved, but tolerance development reduces long-term benefits
Solution Approach 1:
The patent uses periodic action to maintain memory enhancement benefits over the long term by administering DCS intermittently. The treatment-free intervals prevent the neuroadaptive changes that lead to tolerance, ensuring that each subsequent treatment course remains effective. This approach extends the duration of beneficial effects compared to continuous dosing where tolerance would eventually diminish effectiveness.
Solution Approach 2:
The patent changes the temporal parameters of drug administration from continuous to intermittent. By modifying the dosing frequency and introducing drug-free intervals, the invention alters the pharmacokinetic and pharmacodynamic parameters to prevent tolerance development, thereby extending the duration of memory enhancement benefits.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach preserves the benefits of DCS over the long term, reduces drug-related costs and side effects, and is particularly efficacious for mild cognitive impairment, potentially delaying the progression of dementia.
Implementation Method 1
DCS is a partial agonist of the NMDA receptor
Implementation Method 2
DCS, when administered daily for significant periods, induces physiological changes that reduce its activity
Data Source
AI summary
Methods are disclosed for treating dementia, including mild cognitive impairment, via administration of D-cycloserine, or a prodrug thereof, on a tolerance-inhibiting basis. Specifically, by administering D-cycloserine on a tolerance-inhibiting basis, tolerance to D-cycloserine is less likely than would occur via daily administration, enhancing benefits and reducing costs and side effects. Pharmaceutical compositions useful for the treatment of dementia are additionally disclosed.