Invention:
Use of an enzyme, CLN2, to treat Alzheimer's. The enzyme can be administered as a protein, via gene therapy, or introduced to cells which are then administered to patients.

Background:
Fred Maxfield, chair of the Department of Biochemistry at the Weill Cornell Medical College, and Peter Lobel, Department of Pharmacology at UMDNJ-Robert Wood Johnson Medical School, have collaborated in the discovery of novel methods to treat Alzheimer's Disease.

Dr. Lobel is an expert in a protein called CLN2, and was the first to isolate it and clone its gene. CLN2, (also called TPP1 or tripeptidyl peptidase I) is an enzyme found in lysosomes. Lysosomes function like garbage disposals -- unwanted material is put into them and chewed up there by enzymes like CLN2. If a person does not produce enough of any given lysosomal enzyme, that person gets a "jammed garbage disposal" - formally, a lysosomal storage disorder. Dr. Maxfield is an expert in lysosomes and especially in the way matter is trafficked to and away from them.

In the course of his research, Dr. Maxfield realized that the buildup of beta-amyloid plaques in the brains of Alzheimer's patients may stem, in part, from the inefficient degradative processing of waste proteins by lysosomes in brain cells called microgial, which function as immune cells and scavengers in the brain.

In an elegant series of experiments, the inventors confirmed that microglial lysosomes are indeed less efficient than lysosomes in other cells.

They also discovered several ways to increase the activity of microglial lysosomes, including by simply inicreasing the amount of enzymes in the lysosomes, directly or via gene therapy (A Majumdar et al., 2007 Neurobiology of Aging). In a series of unpublished experiments, it was found that a single enzyme, CLN2, accounted for nearly 50% of the augmentation generated by administering a pool of enzymes.

Work is ongoing to validate and develop CLN2 as a treatment for Alzheimer's.

File Number: 3969