Plant lectins as carriers of associated drug substances into animal and human cells

Abstract

The current invention involves the use of protein lectins produced by plants including the non-toxic carbohydrate binding subunits (B subunits) of plant “AB toxins” (PTB lectins) as delivery vehicles for mobilizing associated drug substances for delivery to animal and human cells. The resulting protein fusions or conjugates retain lectin carbohydrate specificity for binding to cells and cellular trafficking activity so as to deliver an associated drug compound to the site of disease manifestation. One embodiment of this invention concerns the ability of ricin toxin B subunit, as a model PTB lectin, to deliver enzyme replacement therapeutic drugs to cells of several organs of the body including the brain and central nervous system, eyes, ears, lungs, bone, heart, kidney, liver, and spleen for treating lysosomal diseases.

Description

CROSS-REFERENCE TO RELATED APPLICATION[0001]The present application claims the benefit of U.S. Provisional Application Ser. No. 61 / 653,062, filed May 30, 2012, which is hereby incorporated by reference herein in its entirety, including any figures, tables, nucleic acid sequences, amino acid sequences, or drawings.BACKGROUND OF THE INVENTION[0002]Human and animal diseases can often be treated by supplying drug substances that correct disease symptoms by supplying a biochemical substance not made properly by the body. Examples include but are not limited to enzyme replacement therapies (ERTs) for the treatment of Lysosomal Diseases (LDs) like Hurlers Syndrome (MPS I) or Alzheimer's with corrective enzymes for these genetic or age related developmental diseases. These types of diseases are associated with failure of metabolic processes or function of specific cells and biochemical pathways within the body. A goal of many drug advancement programs is, therefore, focused on directing dru...

AI Technical Summary

Benefits of technology

The invention concerns delivering therapeutic proteins or substances to the sites of disease in the body, including brain, heart, and other organs. This is done by linking or fusing a therapeutic compound to a plant lectin. The method can be used to treat various diseases involving abnormal functions of organs such as brain and CNS. The technical effect of this invention is to provide a way to deliver therapeutic agents to specific disease sites in the body, enhancing their efficacy while minimizing side effects.

Problems solved by technology

When this happens, waste substances may build up to toxic levels that interfere with normal healthy metabolism leading to serious disease symptoms and even death.

The level of threat to life of genetically defective lysosomal enzymes varies, however, depending on how much the mutation reduces the function of a particular enzyme and what bodily functions are most impaired.

Current drugs are more effective in certain organs such as liver and spleen but often much less effective in treating symptoms in such organs as bone, heart, lungs, kidneys, and the CNS (central nervous system) including brain where severe symptoms occur in many LDs.

Poor brain development and neural degeneration of the brain and CNS are some of the most devastating symptoms in LDs.

The tight control in transport of chemicals and proteins across the BBB poses a significant challenge to the delivery of diagnostic / therapeutic proteins, nucleic acids, and other drugs to the brain.

RMT mechanisms are “saturable” and the amount of product and rate by which substances can be mobilized across the BBB are limited by the number of available receptors present on the luminal surface.

Images