Methods of treating 4-repeat tauopathies

Abstract

The present invention relates to the treatment patient with a 4-repeat (4R) tauopathy using a therapeutically effect amount of a rho kinase inhibitor. One preferred inhibitor is fasudil and preferred methods involve the daily oral administration of between 20 and 250 mg of fasudil. Preferred 4R tauopathies treatable according to the invention include progressive supranuclear palsy with Richardson syndrome (PSP-RS) and corticobasal syndrome with probable sporadic corticobasal degeneration.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to U.S. Provisional application 63 / 104,121, filed Oct. 22, 2020, the disclosure of which is incorporated herein by reference in its entirety.BACKGROUND OF THE INVENTION[0002]Proteinopathies are a group of conditions resulting from the improper folding or unfolding of a protein. They typically manifest as neurodegenerative disorders and are characterized by abnormal protein deposits or aggregates thought to result from conformational abnormalities that disrupt the normal placement of hydrophobic regions of the molecule into hydrophilic environments, causing the proteins to become insoluble and / or aggregate. In some cases, such as in prion diseases, the abnormal structures are thought to form nuclei for further protein deposition, initiating a kind of chain reaction of protein aggregation. The culprit proteins often are normal proteins with aggregates being formed after some post-translational modification, ...

AI Technical Summary

Benefits of technology

The patent is about treating a type of brain disease called 4R tauopathy with a drug called fasudil. The treatment involves giving the patient a daily dose of between 70 and 240 mg of fasudil to see if it can help slow down or stop the symptoms of the disease. The study is being led by a team of researchers at the National Institute on Aging (NIA) in the U.S.

Problems solved by technology

At present, there is no effective therapy for any 4R tauopathy.

In fact, every agent tested in the clinic thus far has failed to show an effect and most of these approaches involved directly antagonizing the pathologic effects of tau.

Thus, there is a wealth of evidence that pharmacological approaches and especially those aimed at disrupting tau pathology do not work and there is no expectation that any approach to disrupting tau pathology will work.

Without a complete understanding of the effects of these different mixtures and how they might relate to human metabolism (in males and females), there is no rational way to extrapolate from animal models to humans.

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