Bad news for Eli Lilly Drug Trial/ More thought about beta-amyloid and infection

The Eli Lilly drug that has been in phase III trials has been stopped due to increased risk of skin cancer and, even worse, an acceleration of deterioration of AD compared to the placebo, the opposite of what was hoped for. This is yet another sad turn of events. Steve was in this study but we stopped in the winter due to several side effects; I believe he was on the actual drug for only about a month at that point. His hair started to grow out a very light gold color (one of the known effects that didn't bother us)and when we stopped it, the darker hair grew in again. He had a half inch white stripe work its way out to the tips of his hair! I no longer have any regrets that we pulled him out of the study.

I believe the worsening of AD in people who were on this drug supports infection as at least one important cause of Alzheimer's disease. One group has found that beta-amyloid kills microbes; they tested a number of bacteria, all of which were killed by beta-amyloid, and this group is now looking at viruses, such as herpes simplex, and other microbes (Soscia "The Alzheimer’s Disease-Associated Amyloid b-Protein Isan Antimicrobial Peptide" PLOS March 2010,Volume 5, Issue 3, e9505: www.plosone.org). If a drug is used to suppress the production of beta-amyloid and it normally is part of the brain's defense against infection, then infection could spread more readily and potentially cause more extensive damage to brain tissue. Beta-amyloid may be more prevalent in people with AD because they have chronic, recurrent infections that are provoking this response. So the increase in amyloid may be the aftermath, no the cause of, the process that does cause AD.

Drs. Ruth Itzhaki and Mark Wozniak in the UK have done extensive work looking at the herpes simplex virus as a cause of AD (they have numerous papers on this from 2005 through 2009.) This virus causes fever blisters, can cause shingles (along with the chickenpox virus, a close relative), and also genital herpes. Herpes simplex lives within nerves and the nerves to the face around the mouth orignate deep in the brain. Most people carry this and other viruses by the time they reach old age, but they have found that people who are ApoE4+ are particularly likely to suffer recurrent episodes of fever blisters. these researchers have found this virus within about 90% of the beta-amyloid plaques in the autopsied brains they have looked at, which strongly suggests that beta-amyloid is there to defend the brain against it. They have also found in animals that the herpes virus increases production of beta-amyloid and also induces AD-like tau phosphorylation (production of tangles). They want to study whether suppression of herpes virus with anti-viral medication would be beneficial to people with AD, but have had trouble getting funding for this.

Acyclovir, for example, is taken daily orally by many people to suppress the genital variety of herpes simplex, including woman who are pregnant, to try to prevent spread of the nfection to the newborn. Perhaps such a treatment could decrease the number and severity of outbreaks in the brain as well. Lysine (available OTC) is used to suppress herpes infections and the lauric acid (C:12) and capric acid (C:10)found in coconut oil kill herpes family of viruses by dissolving the lipid capsule around the virus.

It could also be that, even though beta-amyloid is there to fight infection, it causes some of the damage as well; if you think about it, whenever there is inflammation, part of the body's defensive reaction to infection, there can be damage/scarring to the nearby tissue from the inflammation. The infectious agent is the cause of the whole process, but the body's defenses can also cause some collateral damage, in order to preserve the whole person.

I hope work by Itzhaki and others studying infection will be taken more seriously so that they can get the funding they need.