Are safe, effective, and inexpensive treatments for Alzheimer's Disease just over the horizon? Several major pharmaceutical companies are developing treatments to combat the ill effects of amyloid beta on nerve cells within the brain.
Amyloid beta is suspected of playing a key role in AD. Amyloid deposits attach to nerve cells inhibiting the development of nerve connections responsible for normal neurological activity, including access to memory, and cognitive functioning.
As with any drug intended to treat brain related disorders getting a drug to pass the blood brain barrier is one of the first considerations. Only very small molecules can pass into the brain which makes the task of developing such drugs more difficult.
One approach which seems to hold great potential is employing drugs made with molecules too large to pass into the brain, but which bind to Amyloid beta within the blood. By introducing drugs which bind to, and inactivate Amyloid beta in the general blood stream the level of Amyloid beta within the brain can be reduced. This approach may reduce, or avoid possible adverse side effects within the brain itself.
The following excerpt was taken from the National Institute of Health's website, and reviews just one of many studies being conducted toward a treatment of Alzheimer's Disease:
Previous studies have shown that a protein called amyloid beta is toxic to neurons. Amyloid beta accumulates in the brains of people with AD, forming deposits called amyloid plaques that are a hallmark of the disease. Many investigators are looking for ways to reduce the buildup of amyloid in the brain, with the hope that such a treatment would slow or halt AD.
In the new study, investigators report a way to remove amyloid beta from the brain by introducing another protein that binds to amyloid beta and pulls it from the bloodstream. The amyloid is then removed by the kidneys, liver, and spleen. The investigators, led by Berislav Zlokovic, M.D., Ph.D., of the University of Rochester Medical Center in New York, compare the treatment to a sink because it essentially drains the toxic protein away. The work was funded in part by the National Institute of Neurological Disorders and Stroke (NINDS). It is reported in the September 2007 issue of Nature Medicine.
Dr. Zlokovic and his colleagues studied a protein called soluble low-density lipoprotein receptor-related protein (sLRP). They discovered that sLRP normally binds to and inactivates 70 to 90 percent of the amyloid beta found in the body. However, levels of sLRP were approximately 30 percent lower in blood from people with AD than in healthy people. Much of the remaining sLRP in people with AD was damaged by a process called oxidation. The damaged sLRP was much less effective at removing amyloid beta from the bloodstream than the normal protein. "The binding capability is almost all lost," Dr. Zlokovic says.
The researchers developed a super-potent version of sLRP, called LRP-IV, and injected it into mice to see whether it could mimic the effects of normal sLRP. The treatment bound to amyloid beta and prevented it from entering the brain. It also reduced the toxic amyloid that was already in the brain.
“There is a balance between amyloid beta in the brain and in the rest of the body,” Dr. Zlokovic explains. “If we lower the level of amyloid beta circulating in the blood, the levels in the brain go down, too.” The effect is similar to the way statin drugs remove cholesterol from the bloodstream and help to prevent heart disease, he adds.
Dr. Zlokovic's research should be thought of as a "proof of concept" study in that it doesn't introduce any additional theory to how Alzheimer's Disease works, or how can be treated, but it does confirm that by lowering amyloid beta levels in the blood a drop of amyloid beta in the brain results.
Read below for additional information about the relevance of this study:
The study is the first to show that people with AD have reduced levels of sLRP and that sLRP helps remove amyloid beta from the blood, Dr. Zlokovic says. It is still unclear why sLRP levels are lower than normal in people with the disease, he adds. The researchers tested 40 people with AD for mutations in the sLRP gene and did not find any abnormalities. However, previous studies have shown that AD causes oxidative damage to many proteins. The oxidative damage to sLRP may trigger its breakdown, as well as inactivating it.
The findings suggest that LRP-IV might eventually be useful as a therapy to prevent or stop AD in people. However, the investigators first need to develop a form of the protein that could be tested in humans. They also need to conduct many additional studies to evaluate the drug’s safety and to learn more about how it works.
Taken into context against the backdrop of additional studies it seems reasonable to suggest that successful preventatives, and treatments for AD will be available within ten years.
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