Ketogenic Composition for Epigenetic Disorder Treatment
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Mendelian disorders of the epigenetic machinery, such as Kabuki syndrome, result in intellectual disability and dysmorphic features due to imbalances in chromatin states, with existing treatments failing to effectively restore balance between open and closed chromatin states.
Innovation Solution
Administration of a ketogenic composition that induces physiologically acceptable ketosis, including a ketogenic diet or agents like beta-hydroxybutyrate, to promote open chromatin states by inhibiting histone deacetylases, thereby restoring balance between open and closed chromatin states at target genes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional treatments are used for Kabuki syndrome, then existing therapy protocols are maintained, but chromatin state balance is not effectively restored
Solution Approach 1:
The patent changes the metabolic parameter of the subject by inducing ketosis through ketogenic diet or beta-hydroxybutyrate administration. This metabolic shift alters the chromatin state by inhibiting histone deacetylases, thereby restoring the balance between open and closed chromatin states that is disrupted in Kabuki syndrome
Solution Approach 2:
Beta-hydroxybutyrate serves as an intermediary molecule that mediates between the ketogenic composition and the epigenetic machinery. It acts as a histone deacetylase inhibitor, indirectly restoring chromatin balance without directly targeting the defective KMT2D or KDM6A genes
2Reliability
If ketogenic composition is administered to induce ketosis, then open chromatin states are promoted and neurogenesis deficits are ameliorated, but treatment complexity increases
Solution Approach 1:
The ketogenic composition leverages the subject's own metabolic pathways to produce therapeutic effects. By providing ketone bodies or ketogenic substrates, the treatment activates endogenous histone deacetylase inhibition and chromatin remodeling mechanisms without requiring complex external intervention systems
Solution Approach 2:
The treatment changes the metabolic state parameter of the subject from glucose metabolism to ketone metabolism. This parameter change triggers downstream epigenetic effects that restore chromatin balance and improve neurogenesis, achieving therapeutic goals through a single metabolic intervention
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
The approach effectively ameliorates postnatal neurogenesis deficits and improves cognitive functions in subjects with Mendelian disorders of the epigenetic machinery by promoting open chromatin states, as demonstrated in mouse models of Kabuki syndrome.
Implementation Method 1
Administration of a ketogenic composition that induces physiologically acceptable ketosis, including a ketogenic diet or agents like beta-hydroxybutyrate, to promote open chromatin states by inhibiting histone deacetylases
Implementation Method 2
Administration of a ketogenic composition that induces physiologically acceptable ketosis
Data Source
AI summary
A method is provided for treating a Mendelian disorder of the epigenetic machinery (e.g., Kabuki syndrome) in a subject in need thereof. In particular, the method comprises administering to the subject a ketogenic composition in an amount sufficient to produce a physiologically acceptable ketosis in the subject. A method for selecting a subject for treatment of a Mendelian disorder of the epigenetic machinery (e.g., Kabuki syndrome) is also provided. Ketogenic compositions and kits useful for practicing the methods are also provided.