$ILNS featuring Antisenilin for Alzheimer's disea

$ILNS featuring Antisenilin for Alzheimer's disease

This pioneering approach has gained considerable momentum over the past few years, and leading experts in the field have expressed optimism that drugs being developed using the company's proprietary patented technology herald an exciting new era of drug development for safe and effective disease-modifying treatments for Alzheimer's disease ¹ . The company has granted two worldwide non-exclusive licenses to major pharmaceutical companies with products in Phase II and Phase III clinical under Intellect’s ANTISENILIN® patents and patent applications. In addition, the Company is developing its own follow-on generation product, which it believes will be the best-in-class.

Antisenilin Technology – How It Works

The brain is surrounded by and suspended in a liquid cushion called cerebrospinal fluid, which carries nutrients and essential chemicals to and debris away from the brain by a process known as “Bulk Flow”.

Under healthy conditions, flow of cerebrospinal fluid keeps nutrients and toxic metabolites balanced. However, in some older people, flow is reduced so that toxins that are normally carried away accumulate instead. Chief among these toxins is a protein called beta amyloid. (“A-beta” for short). A-beta is the brain cell toxin responsible for Alzheimer’s disease. A-beta is produced from a larger, normal brain protein called the Amyloid Precursor Protein, “APP for short”. APP is a critically important molecule present at the intersections where communications between nerve cells occur. APP is broken down when it is snipped by two cutting enzymes producing A-beta. In some cases, A-beta accumulates because it is over-produced, as is the case in early-onset cases of Alzheimer’s.

A-beta is first formed as a soluble single small molecule. These single forms of A-beta have a tendency to stick together and form clumps of increasing size as more A-beta sticks. These small aggregates attack the cell surface and cause oxidative damage. Eventually, the small clumps accumulate into large clumps, know as plaques. This progressive increase in aggregation results in additional harm to the brain, as white blood cells and antibodies from the immune system attack the clumps in a futile attempt to destroy them. Inflammation is the result of this immune attack, and inflammation causes additional damage to the brain.

Tangles are another microscopic form of toxic molecules. Tangles form inside the nerve cells and lead to further damage. The combination of A-beta toxicity outside the brain cell and tangles inside over time results in irreversible damage to brain cells, loss of connections between nerve cells and cell death. The first area in the brain to show this Alzheimer’s pathology is the hippocampus – the memory maker of the brain. The clinical result is loss of memory, and is followed by loss of other brain functions such as the ability to learn, communicate with language, and behave appropriately.

Dr. Chain’s approach consists of a safe way to remove A-beta protein, ensuring that the normal function of the important APP molecule is not affected. Given almost any substance, it is possible to create very specific antibodies called monoclonal antibodies. A monoclonal antibody will bind to the substance it was created against and will not bind normal molecules. Dr. Chain’s approach pinpoints unique molecular signatures at either end of A-beta which are not present in APP. ANTISENILIN antibodies only bind these molecular signatures, thus safely helping to shuttle A- beta away from sites of damage in the brain while leaving APP untouched and thus able to function normally. These free-end specific antibodies can also be made to bind aggregated forms of A?, including oligomers, and amyloid plaques.

Figure 1: ANTISENILIN ^® antibodies target either end of A?

Bapineuzumab, which binds to the free amino (NH ₂ ) terminus of Aß, is being tested in Phase III Clinical Trials by Janssen, a subsidiary of Johnson & Johnson and Wyeth/Pfizer.