Biologics and cleaving APP for AD

Michele K.

9/1/2007 8:53:59 PM

In the "Risks and Rewards of Biologics for the Brain", (July, 2007) the authors included information about Dr. Kohler and Dr. Milstein discovering enzymes that were able to cleave DNA at specific locations. Although not specifically stated, it appears that this technology was developed in the 1970s, therefore, the splicing of smaller particles, such as proteins, should or could be possible.

According to the 2005-2006 Progress Report on Alzheimer's disease (AD), one of the theories as to the origin of the disease is where the protein APP is cleaved in the neuronal membrane. Depending on which enzyme cleaves APP (alpha secretase, beta-secretase, and gamma secretase) and where the cleaving happens, the APP processing can follow two pathways, one that has healthy implications for the brain and another that may start the process for AD. If the APP protein is cleaved by beta-secretase, there is a potential that one end of the fragment can become beta-amyloid. A beta-amyloid peptide is released into the space outside the neuron, which eventually results in similar peptides adhering together, forming oligomers, which then coalesce into plaques that are characteristic of AD.

Has the use of biologics for the brain, specifically for cleaving the APP protein, been considered or studied for intervention of AD? Drs. Dorsey, Vitticore and Moses state that biologics have the potential to be successful in genetics having to do with gene expression. Because four genes attached to four chromosomes and their mutation or alleles may be a huge contributing factor to the development of AD, wouldn’t biologics be a natural and vital area for further research?