ROAD TO THE CURE UPDATE SEPTEMBER 2012

The failure of a recent large clinical trial of one of the Alzheimer’s drugs, Bapineuzumab, undertaken by pharmaceutical giants Johnson and Johnson, Pfizer and Eli Lilly, is a somber reminder of:

• The complex pathology of neurodegenerative Alzheimer’s disease. The same is true for Parkinson’s disease.
• The Blood-brain barrier penetration of a drug intended for treating brain disease is one of the key requisites for an optimal therapeutic index.
• Wealth does not necessarily equate to technological success.

This news must have been an extremely disappointing and demoralizing affect on Alzheimer’s patients and their loved ones as their long cherished hopes were simply dashed into the ground. But the failure of Bapineuzumab should not have come as a big surprise. About two years ago, the clinical trial of the same drug on a small number of patients was halted due to the serious side effects such as brain inflammation. It was surprising these pharmaceutical companies decided to go ahead with a larger clinical trial with the same drug.

The failure of Bapineuzumab could have been due to several reasons: 1) Inefficient Blood-brain barrier penetration; 2) Toxicity; 3) Lack of the interaction with the soluble form of amyloid-plaque, which is linked to cognitive decline; 4) Complex multi-pathology of Alzheimer’s disease, which refers to the involvement of multiple disease causing pathogens such as Tau tangles and truncated ApoE4 proteins. While the presence of large amounts of insoluble amyloid-plaque in individuals has been shown not to cause dementia, the presence of a small amount of Tau tangles in the brain is known to cause dementia. Therefore, it is the opinion of the scientists at the biotech Company in San Diego that expecting a single drug such as Bapineuzumab to improve cognitive function was, at the very least, very naïve.

The San Diego Company already has measures in place to avoid the repeat of a colossal failure of a drug such as Bapineuzumab. This Company’s emphasis not only has been to develop and continue improving technology for improved blood-brain barrier penetration, its emphasis right from its inception has also been to develop blood-brain barrier penetratable multi-target picobodies to modulate the function of multiple pathogens in Alzheimer’s and Parkinson’s patients. For Parkinson’s disease in particular, this Company has already developed picobodies for two of disease pathogens; a-synuclein and mutant LRRK2.  Efforts are underway to develop picobodies for other targets as well.