Joslin Diabetes Center, Inc.

Eli Lilly and Company

The Charles Stark Draper Laboratory, Inc.

Activesite Pharmaceuticals, Inc.

Lloyd Paul Aiello

Michael R Jirousek

Douglas Kirk Ways

George Liang King

Louis Vignati

Edward P Feener

Sukanto Sinha

Tamie Chilcote

Rami S Mangoubi

Mukund Desai

Joseph J Danko

The present invention provides methods and composition for the treatment and diagnosis of disorders associated with excessive vascular permeability and edema.

Compositions and methods for treating vascular permeability

The systems and methods described herein relate generally to the detection of retinal abnormalities. More particularly, the systems and methods are used to analyze a fundus or other image of the retina. In some implementations, the image is analyzed by interdependently smoothing and segmenting the image. Using the smoothed and segmented image, retinal features can be identifying in the image. The systems and methods can then analyze the detected retinal features to identify retinal abnormalities.

Systems and methods for detecting retinal abnormalities

We have identified classes of kallikrein inhibitors as compounds that are useful in the reduction of vascular permeability (e.g., retinal vascular permeability and cerebral vascular permeability) and astrocyte activation. Diseases and conditions associated with increased vascular permeability include diabetic retinopathy, hemorrhagic stroke, and macular edema. Diseases and conditions associated with astrocyte activation include Alzheimer's disease, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, stroke, epilepsy, and brain trauma.

Methods for treatment of kallikrein-related disorders

A method for inhibiting VEGF stimulated endothelial cell growth, such as associated with neoplasia, and VEGF stimulated capillary permeability, such as associated with pulmonary edema are disclosed, particularly using the &bgr;-isozyme selective PKC inhibitor, (S)-3,4-&lsqb;N,N&prime;-1,1&prime;-((2&Prime;-ethoxy)-3&prime;&Prime;(O)-4&prime;&Prime;-(N,N-dimethylamino)-butane)-bis-(3,3&prime;-indolyl)&rsqb;-1(H)-pyrrole-2,5-dionehydrochloridesalt.

Therapeutic treatment for VEGF related diseases

A method for inhibiting VEGF stimulated endothelial cell growth, such as associated with macular degeneration, and VEGF stimulated capillary permeability, such as associated with macular edema are disclosed, particularly using the isozyme selective PKC inhibitor, (S)-3,4-[N,N'-1,1'-((2'-ethoxy)-3''(O)-4''-(N,N-dimethylamino)-butane)-bis -(3,3'-indoly 1)]-1(H)-pyrrole-2,5-dionehydrochloridesalt.

Therapeutic treatment for VEGF related ocular diseases

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Belmont, MA, United States of America

Lloyd Paul Aiello