Treatment of cerebral cavernous malformations and cerebral aneurysms with rho kinase inhibitors

Inventors

Rosen, Kenneth M. • Riesinger, Steven Wayne • McKerracher, Lisa • Bond Moritz, Lisa

Assignees

Bioaxone Biosciences Inc

Abstract

Provided are methods of treating a cerebral cavernous malformation (CCM) and methods of treating cerebral aneurysm in a mammal with certain rho kinase inhibitors.

Core Innovation

The disclosure describes treating or preventing cerebral cavernous malformations (CCMs) and cerebral aneurysms by administering selective ROCK2-targeting rho kinase inhibitors. It links rho/ROCK overactivation to endothelial barrier disruption, vascular leakage, impaired angiogenesis, and inflammatory wall damage, and uses ROCK inhibition to reduce CCM lesion formation and maturation and to reduce cerebral aneurysm number and size while preventing maturation into complex lesions.

The invention relates to a therapeutic method in a mammal affected by a cerebral aneurysm, using a therapeutically effective amount of a pharmaceutical formulation containing a compound selected from a specified group, including pharmaceutically acceptable salts thereof. The formulation is directed to a rho kinase inhibitor context, and the treatment is framed as a method of therapy in a mammal.

The disclosure further encompasses combination approaches by including at least a second rho kinase inhibitor in addition to the compound of the pharmaceutical formulation. The second rho kinase inhibitor can be selected from enumerated named compounds, and the method allows pharmaceutically acceptable salts or mixtures thereof. It also includes oral administration, tablet or capsule embodiments, and BA-1049 (racemate) and BA-1049 (R) enantiomer as therapeutically active compounds.

Claims Coverage

The relevant independent claims are clm-00001 and clm-00008. Across these independent claims, the core inventive coverage involves treating a cerebral aneurysm in a mammal using a therapeutically effective amount of a pharmaceutical formulation containing a specified compound selection, and a defined chemical structure with an (R)-enantiomer option, with optional inclusion of a second rho kinase inhibitor in dependent refinements.

Across the independent claims, the core claim coverage is methods for treating cerebral aneurysm in a mammal via pharmaceutical formulations containing a selected ROCK inhibitor compound, including a specified chemical structure and/or the (R)-enantiomer, with pharmaceutically acceptable salts, with dependent coverage for adding a second rho kinase inhibitor from a named set and for presenting the formulation as tablet or capsule.

Stated Advantages

Documented Applications