Methods for treating alzheimer disease and for reducing amyloid beta formation

Abstract

The present invention provides methods for reducing amyloid beta formation and for treating diseases associated with IC the accumulation of amyloid beta, The present invention provides (1) A β aggregation inhibition by A β Oligomer / Fibril formation inhibition, (2) BACE-1 reduced a through β-Amyloidogenic Processing inhibition, (3) cerebral blood flow to the increase of the cell outer Aβ Monomer, Oligomer & Aβ Fibril / Plaque reduction, (4) NO / cGMP / PKG / CREB Pathway to the activation of Neuronal cell Death inhibition and Neurogenesis, Synaptogenesis, Angiogenesis promotion, (5) DKK-1 inhibition by Wnt Signaling in the activation of synaptic plasticity recovery and Aβ production Positive Feedback Loop for inhibition of APP generates reduced and Aβ accumulation suppression, (6) Autophagy activation by cells within Toxic Mirodenafil, Sildenafil, Vardenafil, Tadalafil, Udenafil, Dasantafil, and Avanafil for the treatment of inhibition of Aβ Fibril / Plaque formation through removal of Soluble Aβ Oligomer; and a Pharmaceutically Acceptable Salt, Solvate, and Hydrate in selected compounds key of ingredient containing drug compound composition, and this with the treatment method provided.

Description

CROSS-REFERENCE TO RELATED APPLICATION[0001]This application claims the benefit of priority from U.S. Provisional Application Ser. No. 62 / 822,975, filed Mar. 24, 2019, the contents of which are incorporated herein by reference.FIELD OF THE INVENTION[0002]The present invention is related to methods for reducing amyloid beta formation and for treating diseases associated with the accumulation of amyloid beta.BACKGROUND OF THE INVENTION[0003]Dementia refers to a clinical disease that suffers from multiple cognitive impairment (or MCD, Multiple Cognitive Deficits) as an acquired brain disease that shows multifaceted pathogenesis caused by a variety of genetic and environmental risk factors. A representative of diseases causing dementia is Alzheimer's disease, mainly endemic in senior people and contributed to 60-70% of the all dementia (Ann Neurol. 1993 May; 33(5): 494-501). Recent rapid aging of population, more progressive dementia in older people by Alzheimer's has increased and so d...

AI Technical Summary

Benefits of technology

The patent describes a method to prevent the formation of harmful plaques in the brain associated with Alzheimer's disease by using certain drugs such as Mirodenafil, Sildenafil, and Vardenafil. These drugs are designed to remove toxic soluble Aβ oligomers from cells in the brain. The technical effect of this method is to potentially reduce the risk of Alzheimer's disease by reducing the buildup of harmful plaques in the brain.

Problems solved by technology

However, the difficulties of research and development in additional low rate of success down the process of development of new therapeutics and treatment method for dementia.

However, these drugs are used only to relieve symptoms and delay or improvement of cognitive disorders, but there is no fundamental treatment for dementia at this moment.

However, so far no clear evidence was found that the combination of AChE inhibitors and Menantine is more effective than AChE alone and additional study is required (Brain Neurorehabil 2015 March; 8(1): 19-23).

However, even though these drugs have been used for treatment of dementia and Alzheirmer's disease for a long time, there is no clear standard for the usage and furthermore, even at the maximum recommended human dose (MRHD), either there was only no improvement or continued progress of the disease to lead the patients to the terminal stage in the treated patients, there has been a continuous concern with the usage of these drugs.

However, until now in the absence of any therapeutics with confirmed efficacy, there is no alternatives but to continue the effort to develop new treatment for dementia (Korean J Biol Psychiatry 2016 May; 23(2): 48-56.).

However, due to the recent failures of clinical trials of candidates with high expectation, including Anti-Aβ Monoclonal Antibody targeting Aβ for targeted such as Aducanumab (Biogen), Solanezumab (Eli Lilly), and Gantenerumab (Roche), the assumption of Aβ as the target for treatment of dementia became uncertain.

One of the issues of Aβ targeted drug development is that it is very difficult for the monoclonal antibodies having large molecular weight to penetrate the cell membrane and thus, it can be effective only to remove extracellular amyloid plaque, and has only limited efficacy for the removal of intracellular Aβ oligomers.

It is being accepted that this traditional approach cannot achieve a successful development of therapeutics for dementia.

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