Alpha-aminoamide derivatives useful in the treatment of cognitive disorders
Inventors
Salvati, Patricia • Rossetti, Stefano • Benatti, Luca
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-8741957-B2
Publication Date
2014-06-03
Expiration Date
Abstract
The present invention is in the field of pharmacotherapy of cognitive deficits in learning and memory by administering an α-aminoamide, particularly safinamide. Examples of disturbances in cognition that can be treated with compounds of the invention are the ones associated with disorders such as autism, dyslexia, attention deficit hyperactivity disorder, schizophrenia, obsessive compulsive disorders, psychosis, bipolar disorders, depression, Tourette's syndrome, Mild Cognitive Impairment (MCI) and disorders of learning in children, adolescents and adults, Age Associated Memory Impairment, Age Associated Cognitive Decline, Alzheimer's Disease, Parkinson's Disease, Down's Syndrome, traumatic brain injury Huntington's Disease, Progressive Supranuclear Palsy (PSP), HIV, stroke, vascular diseases, Pick's or Creutzfeldt-Jacob diseases, multiple sclerosis (MS), other white matter disorders and drug-induced cognitive worsening.
Core Innovation
The invention relates to a method of improving cognitive function and treating cognitive impairment by administering to a patient in need thereof a therapeutically effective amount of an alpha-aminoamide of formula (I) with defined structural constraints, including isomers, mixtures, and pharmaceutically acceptable salts or esters. The method is directed to cognitive impairment as such, and to cognitive deficits associated with a broad set of diseases and conditions.
The document frames the cognitive-treatment approach around alpha-aminoamide activity described as not being a cholinesterase inhibitor. Safinamide is characterized as a selective MAO-B inhibitor and a glutamate release inhibitor, and the invention emphasizes unexpectedly positive cognitive effects associated with safinamide administration, including when added to dopamine agonist therapy in early Parkinson’s disease, where DA-associated cognitive worsening is counteracted.
The disclosed treatment concept includes administering an alpha-aminoamide compound of formula (I) either alone or as part of combination therapy in which cholinesterase inhibitors and/or acetylcholine modulators are administered together with the alpha-aminoamide. A clinical example described in the document uses a cognitive test battery with a Phase III double-blind, randomized, placebo-controlled design and reports cognitive improvements for safinamide arms versus a dopamine-agonist-alone control, alongside motor score improvements and a favorable safety profile.
Claims Coverage
Two independent claims are provided. Across these claims, the inventive coverage centers on a formula (I) alpha-aminoamide used to improve cognitive function and treat cognitive impairment, with one claim additionally requiring combination therapy with cholinesterase inhibitors and/or acetylcholine modulators and restricting the cognitive impairment to a specified disease-associated list.
Formula (I) alpha-aminoamide for cognitive function improvement
A method of improving cognitive function and treating cognitive impairment by administering to a patient in need thereof a therapeutically effective amount of a compound consisting of an alpha-aminoamide of formula (I) with defined structural constraints, including isomers, mixtures, and pharmaceutically acceptable salts or esters thereof.
Combination therapy with cholinesterase inhibitors/acetylcholine modulators for disease-associated cognitive impairment
A method of improving cognitive function and treating cognitive impairment associated with a disease selected from the stated group by administering to a patient a combination therapy consisting of cholinesterase inhibitors and/or acetylcholine modulators with a therapeutically effective amount of an alpha-aminoamide compound of formula (I) having the defined structural constraints, including isomers, mixtures, and pharmaceutically acceptable salts or esters thereof.
Overall, claim coverage is directed to administering defined alpha-aminoamide compounds of formula (I) to improve cognitive function and treat cognitive impairment, either as monotherapy or in combination with cholinesterase inhibitors and/or acetylcholine modulators for cognitive impairment associated with a specified list of diseases.
Stated Advantages
Unexpectedly positive cognitive effects, including counteracting DA-associated cognitive worsening in early Parkinson’s disease when safinamide is added to dopamine agonist therapy.
Improving motor scores while maintaining a favorable safety profile.
Documented Applications
Treatment of cognitive deficits across conditions including MCI, autism, schizophrenia, Alzheimer’s disease, Parkinson’s disease, traumatic brain injury, HIV, stroke, and vascular diseases, using safinamide-based alpha-aminoamide administration.
Clinical example using a cognitive test battery with a Phase III double-blind randomized placebo-controlled design reporting cognitive improvements for safinamide arms versus dopamine-agonist-alone control.
Interested in licensing this patent?