Use of genomic testing and ketogenic compounds for treatment of reduced cognitive function
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9175345-B2
Publication Date
2015-11-03
Expiration Date
Abstract
This invention relates to methods of using genotyping to select patients for treatment with compounds capable of elevating ketone body concentrations in amounts effective to treat reduced neuronal metabolism associated with reduced neuronal metabolism, for example Alzheimer's disease.
Core Innovation
The invention relates to a method of treatment for Alzheimer’s disease by selecting a human patient having, or at risk of, Alzheimer’s disease. The method determines the presence of at least one specific genotype selected from heterozygosity for C/T for Insulin Degrading Enzyme (IDE) rs 2251101 and absence of homozygosity for C/C of IDE rs 2251101, as defined by a relevant portion shown by SEQ ID NO:3.
The selected patient having at least one of the specific genotypes is treated by administering a composition comprising an effective amount of medium chain triglycerides (MCT). The MCT composition is defined as a formula wherein the R1, R2, and R3 esterified to the glycerol backbone are each independently fatty acids having 5-12 carbon chains.
The disclosure further frames the treatment strategy around patient response to ketogenic therapies, linking reduced neuronal metabolism to indications and associating patient-specific genotype criteria with response to administering compounds that elevate ketone body concentrations. In this context, D-beta-hydroxybutyrate (BHB) is referenced as a ketone body measure, including genotype-dependent effects in an illustrative Alzheimer’s pharmacogenomics study.
Claims Coverage
The independent claim describes a treatment method that combines patient selection based on genotype criteria with administration of a defined medium chain triglycerides (MCT) composition. The independent claim includes 1 inventive feature set, and dependent claims further refine patient selection and/or the MCT composition attributes and dosing-related ranges.
Genotype-selected Alzheimer’s treatment with IDE rs 2251101 criteria
Selecting a human patient having, or at risk of, Alzheimer’s disease, determining the presence of at least one specific genotype selected from heterozygosity for C/T for Insulin Degrading Enzyme (IDE) rs 2251101 and absence of homozygosity for C/C of IDE rs 2251101, as defined by a relevant portion shown by SEQ ID NO:3.
Administering MCT composition with 5-12 carbon chain fatty acids
Administering to the patient having at least one of the specific genotypes an effective amount of a medium chain triglycerides (MCT) composition defined by a formula in which R1, R2, and R3 are each independently fatty acids having 5-12 carbon chains esterified to the glycerol backbone.
Refined treatment using additional ApoE4 genotype testing
Testing for absence of the ApoE4 genotype as an additional criterion in the method.
Oral MCT composition including glucose
Characterizing the method by using an oral composition that further includes glucose.
Quantitative D-beta-hydroxybutyrate blood-level increase range
Administering the composition at an effective dose to increase a patient’s blood D-beta-hydroxybutyrate level from about 0.1 mM to about 50 mM, and in another refinement from about 0.2 mM to about 5 mM.
Quantitative daily dosage range
Administering the composition at a daily dosage ranging from about 0.05 g/kg/day to about 10 g/kg/day.
Overall, the claim set covers genotype-based patient selection, including IDE rs 2251101 criteria and, in dependent form, absence of ApoE4, followed by administration of an MCT composition defined by fatty acids having 5-12 carbon chains, with dependent refinements specifying an oral formulation including glucose and quantitative ranges related to D-beta-hydroxybutyrate blood levels and daily dosage.
Stated Advantages
Provides a genotype-guided treatment strategy for Alzheimer’s disease by selecting patients having specific genotypes for IDE rs 2251101 criteria.
Associates genotype-selected administration of ketogenic therapy-related compounds with genotype-dependent effects using D-beta-hydroxybutyrate (BHB) measurements and neuropsychological outcomes.
Documented Applications
Illustrative Alzheimer’s pharmacogenomics study KET-04-001 using AC-1202 (MCT) with reported genotype-dependent effects on ADAS-Cog and biomarker responses (BHB).
Patient-selection strategy for reduced cognitive function/Alzheimer’s disease by genotyping polymorphisms associated with response to ketogenic therapies.
Interested in licensing this patent?