University Health Network

Amorfix Life Sciences Limited

Leland Stanford Junior University

Promis Neurosciences Inc.

Rishi Rakhit

Avijit Chakrabartty

Neil R Cashman

Joachim Bernhard Ostermann

Anita Antoinette Bugyei-Twum

Thomas J Wandless

Kimberly M Bonger

The disclosure pertains to antibodies and binding fragments thereof that specifically binds all or part of EHAEVVFTA. Also provided are isolated peptides, isolated nucleic acids, immunogens, compositions, immunoassays and kits and method of using said reagents to detect misfolded TTR.

Antibodies to TTR and methods of use

The invention provides a method for treating a medical condition, disease, or disorder mediated by a misfolded form of superoxide dismutase (SOD) in a subject in need of treatment. The method optionally comprises administering to the subject a composition comprising a pharmaceutically acceptable vehicle and an agent selected from (1) an exogenous antibody or fragment thereof that binds selectively to the misfolded form of SOD, and/or (2) an immunogen that elicits production of an endogenous antibody that binds selectively to the misfolded form of SOD, and/or (3) a nucleic acid sequence encoding (1) or (2). In certain embodiments, the invention provides methods of treating diseases such as Alzheimer's Disease, Parkinson's Disease or amyotrophic lateral sclerosis using amyotrophic disease-specific epitopes, and compositions including these epitopes. The invention also provides antibodies that bind to monomeric or misfolded SOD1, and not on the molecular surface of native homodimeric SOD1. In addition, the invention includes methods of diagnosing Alzheimer's Disease, Parkinson's Disease or amyotrophic lateral sclerosis in a subject. Also, the invention provides methods of identifying substances for the treatment or prevention of Alzheimer's Disease, Parkinson's Disease or amyotrophic lateral sclerosis and kits using the binding proteins of the invention.

Methods and compositions to treat and detect misfolded-SOD1 mediated diseases

Disclosed herein are a light-inducible system and method for rapidly and reversibly modulating protein stability and function. This system and method employs conditionally stable protein domains that regulate the degradation of a fusion protein depending upon the presence or absence of a particular light source.

Light-inducible system for regulating protein stability

The invention provides a method for treating a medical condition, disease, or disorder mediated by a misfolded form of superoxide dismutase (SOD) in a subject in need of treatment. The method optionally comprises administering to the subject a composition comprising a pharmaceutically acceptable vehicle and an agent selected from (1) an exogenous antibody or fragment thereof that binds selectively to the misfolded form of SOD, and/or (2) an immunogen that elicits production of an endogenous antibody that binds selectively to the misfolded form of SOD, and/or (3) a nucleic acid sequence encoding (1) or (2). In certain embodiments, the invention provides methods of treating diseases such as Alzheimer's Disease, Parkinson's Disease or amyotrophic lateral sclerosis and macular degeneration, glaucoma, ischemia, cerebral infarction, myocardial infarction, atherosclerosis, multiple sclerosis, inflammatory bowel disease, ulcerative colitis, Crohn's disease or necrotizing enterocolitis using disease-specific epitopes, and compositions including these epitopes. The invention also provides antibodies that bind to monomeric or misfolded SOD1, and not on the molecular surface of native homodimeric SOD1. In addition, the invention includes methods of diagnosing Alzheimer's Disease, Parkinson's Disease or amyotrophic lateral sclerosis in a subject. Also, the invention provides methods of identifying substances for the treatment or prevention of Alzheimer's Disease, Parkinson's Disease or amyotrophic lateral sclerosis and kits using the binding proteins of the invention.

The invention provides binding proteins that bind to misfolded or monomeric SOD1, and not to native homodimeric SOD1. The invention also includes methods of diagnosing, detecting or monitoring amyotrophic lateral sclerosis in a subject. In addition, the invention provides methods of identifying substances for the treatment or prevention of amyotrophic lateral sclerosis and kits using the binding proteins of the invention.

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Toronto, Canada

Rishi Rakhit