New Type of Alzheimer’s Drug May Prevent, Slow or Treat The Disease

Daniel Chain, Ph.D, the son of a Nobel Prize Winner and a distinguished neurobiologist himself, woke up one Sunday night 1996 and had a sudden inspiration– “Why not monocolonal antibodies?”

Chairman and chief executive officer of Manhattan-based Intellect Neurosciences, Dr.
Chain, a distinguished neurobiologist, was interested in finding a innovative medication
that can slow down, arrest and ultimately prevent Alzheimer’s disease – a devastating condition afflicting 30 million people worldwide. Contrary to drugs currently on the market, which only treat symptoms, Dr. Chain’s aims was to create a new class of disease-modifying Alzheimer’s drugs that attack the underlying pathologies.

Monclonal Antibodies

Moncolonal antibodies are a type of protein made in the laboratory that can find and bind to a specific substance. Could a monoclonal antibody be developed that would latch on to amyloid, a dense deposit of protein found as plaques on the cells and nerves of Alzheimer’s patients at autopsy? There is no unanimous agreement that amyloid plaques are the cause of the condition but may be just a symptom or an extraneous factor.

Amyloid plaques were first noted by Dr. Louis Alzheimer’s in 1906 . The main constituent of the plaques is the Beta Amyloid protein which is comprised of fragments of a much larger protein called the Amyloid Precursor Protein (APP) implicated in regulating numerous physiological functions in the body. Beta Amyloid can accumulate for different reasons in the brain. The naturally sticky fragments form clumps that increase in number and density until eventually, the clumps deposit as insoluble plaques onto the surface of nerve cells. Are these plaques toxic? Are they beneficial? Do their roles change at different stages of the disease? As the plaques mature in the brain they trigger inflammation which damages the cells causing them to die.

Toxic Substance Floating In Brain Fluid

Dr. Chain now believes that there is a toxic substance floating around in brain fluid that is a precursor to amyloid clumps and plaques.

“Perhaps,” he reasons, “the plaques of hardened amyloid found on the brain cells of Alzheimer’s patients may be the way the brain protects itself from the toxic amyloid precursor.”

Drug Companies At Work On The New Type of Drug
He says he decided to develop a method of harnessing certain monoclonal antibodies that he believes can be used to render the precursor harmless and thus prevent or improve Alzheimer’s destruction of the brain cells.

Dr. Chain was successful and he patented the technique he developed and called it Antesenilin. His invention is currently being used by several of the world’s largest pharmaceutical companies which have taken licenses to Dr. Chain’s patents from which Intellect Neurosciences stands to obtain royalties from sales if and when the drugs are approved by the FDA pending completion of clinical trials. The most advanced product, Bapineuzumab, is in Phase 3 trials involving several thousand Alzheimer’s patients world-wide. Bapineuzumab is being co-developed by Wyeth/Pfizer and Johnson & Johnson. Dr. Chain’s patents have already been granted in Europe, Japan, China and elsewhere

Dr. Chain points out there are two basic types of Alzheimer’s. One that occurs in 5 to 10 percent relatively early 40-50 and invariably have a genetic pre-disposition .carried in families .The other starts later about 65 years and up and has known and unknown causes.

He said the tests first conducted with Bapineuzumab, involved a small group about 250 patients: “They did not separate out those with the gene for the disease and those who developed it later in life. It did seem to indicate that those who developed it later in life were benefited by the drug but not those who carried the gene.”

A study involving several thousand people –separating the two types of Alzheimer’s—are now underway.

Bapineuzumab May Be On The Market Within Three Years

Dr. Chain said he hopes that within three years, Bapineuzumab will be on the market.

What about side-effects?

So far, he said, he, there is some edema—(swelling) –but it goes away and in lower doses it does not occur. at all.

Can water pollution affect the genitals of both girls and boys?

There have been numerous articles lately in scientific journals about the average age of puberty decreasing in American girls. Richard H. Reindollar, M.D. – Professor and Chair, Department of Obstetrics and Gynecology, Dartmouth Hitchcock Medical Center, Dartmouth Medical School, Lebanon, New Hampshire and his colleagues, for example, wrote on’s website, an international source of information for physicians, overall incidence of sexual precocity has been estimated to be 1:5,000 to 1:10,000 children. The female to male ratio is approximately 10:1

The classic definition of sexual precocity is the appearance of secondary sexual characteristics before the age of 8 years. The phenomenon was revealed in a study published in 1997 by a research team led by Dr. Herman-Giddens. Pediatricians around the country rated sexual maturation in 17,077 girls ages 3 to 12. The study’s conclusion was breasts and/or pubic hairs were far more common in 7- and 8-year-olds than medical textbooks had been reporting.

The scientists now studying premature sexual maturation in girls are mostly blaming it on children being overweight. The scientists point out fat releases hormones which could lead to premature puberty.

Dr. Frank Brio, the director of adolescent medicine at Cincinnati Children’s Hospital Medical Center, was quoted in the NY Times as agreeing that overweight girls were more likely to have breast development but added it was possible that environmental chemicals were also playing a role.

“It’s certainly throwing up a warning flag,” Dr. Biro said. “I think we need to think about the stuff we’re exposing our bodies to and the bodies of our kids. This is a wake-up call, and I think we need to pay attention to it.”

What chemicals in the environment may affect hormones?

So-called Endocrine Disrupting Compounds (EDC’s) are chemicals that mimic the body’s natural hormones, according to JA. Katzenellenbogen, professor of chemistry at the University of Illinois, writing in Environmental health in 1995: “They are environmental agents that interfere with the production, release, transport, metabolism, binding, action or elimination of natural hormones in the body responsible for the maintenance of homeostasis and the regulation of developmental processes.”

There have been many reports about EDCs adversely affecting sperm production in male and causing birth defects in male fetuses. David Norris, PhD, an integrative physiology professor at the University of Colorado at Boulder, for example, recently reported at the 92nd Endocrine Society’s meeting in San Francisco fish swimming in polluted waters may be the “canaries” alerting humans about endocrine disrupters. He says that even though the levels of the chemicals in waters fish swam in were very low, the substances proved to be endocrine disrupters.

How do EDCs Get In our Water?

One of the answers to EDCs in water may be our use of Personal Care Products. In 2008 a study carried out on behalf of the Environmental Working Group (EWG) claimed that 95 percent of the waterways in the San Francisco Bay area were contaminated with EDCs traced to personal care products.

In March 2009, still another study from the Baylor University showed that fish samples from US waterways are frequently contained residues of personal care products. Working with the US Environment Protection Agency (EPA), the Texas scientists reported they also detected low-level residues of several human medications.

Medicines in the water

While the study found the residue of several pharmaceutical and personal care products in fish tissue, it also demonstrated for the first time that fish from several locations across the country are exposed to multiple pharmaceutical and personal care products (PPCPs) in effluent-dominated waterways, according to Dr. Bryan Brooks, associate professor at Baylor University.

The US Environmental Agency (EPA) made a pledge in August 2008 to further investigate the effects PPCPs have on the nation’s waterways. The EPA-sponsored scientists tested for 36 different compounds in fish samples sourced at effluent-dominated waterways – 24 originating form medicines and 12 originating from personal care products. Of this total, the scientists found the residues of two compounds from personal care products and seven compounds commonly found in pharmaceutical products.

The two personal care compounds were galaxolide and tonalide, both fragrances that are used in a wide variety of soaps and other personal care products.

Feminized Male Fish

Although the scientists say the impact of all these compounds on the fish is not fully understood, the researchers stress there is documented evidence to suggest the contaminants lead to changes in behavioral patterns that influence fish survival.

Dr. Norris reported at the recent Endocrine Society meeting 18 out of the 19 wastewater samples that were examined contained trace levels of Bisphenol A. It is used in plastic baby bottles; food and beverage can linings and other products. The Centers for Disease Control estimated in 2004 that 95 percent of Americans have the chemical in their urine. A 2007 report from the US National Toxicology Program and the National Institutes of Health concluded Bisphenol A presents “some concern” about exposure of fetuses and children at current human exposure.

Future Generations May Be Affected

Are EDCs contributing to the early sexual development of girls?

Are EDCs leading to feminization of boys?

Dr. Norris warned at the recent Endocrine Society meeting: “The fish are a wake-up call. Our bodies and those of the much more sensitive human fetus are being exposed everyday to a variety of chemicals that are capable of altering not only our development and physiology but that of future generations as well.”

Resources: Chemicals Remaining after Wastewater Treatment Change the Gender of Fish

Released: 6/21/2010 12:15 PM EDT

Source: Endocrine Society

Arizona Department of Environmental Quality

JA. Katzenellenbogen , Environmental health Health Perspect. 103 Suppl 7:99-101(1995)