June 27, 2012

Alzheimer's: Where Are We?

I’ve often said in this space that – although I already have prostate cancer and Parkinson’s disease – what I fear most is Alzheimer’s. I’ll bet many of you feel the same way.

So, in my daily travels across the internet, I watch for information about the progress researchers are making in their quests for treatments. Here’s a quickie, elementary “primer.”

The most promising research is addressing two different “hallmarks” of the disease:
  1. amyloid plaques, and 
  2. neurofibrillary tangles. 

Amyloid plaques are protein accumulations in the brain that interfere with communication between brain cells, or neurons. Those message disruptions produce the classic symptoms of AD and dementia, including memory loss.

Scientists now pursue two different therapies to prevent plaque accumulation: vaccine and drugs.

Vaccinations inject either beta amyloid (to create antibodies against the protein, limiting its accumulation) or the antibodies themselves. Both these vaccinations remain under careful study, and – while promising – have also caused serious adverse reactions.

Drug therapies
Researchers are targeting two enzymes involved in the development of amyloid plague accumulation. A new drug – PBT2 – may inhibit the enzymes’ ability to create dangerous plaques, but it may also disrupt other important brain activities controlled by the enzymes. Like the vaccines, drug therapies for AD have a long road ahead.

As is the case with plagues, the culprit with tangles is also a protein, in this case, “tau.” In AD patients, tau ends up clumping into twisted fibers that seem to eventually kill brain cells. In normal brains, this protein helps move nutrients around inside the brain.

In 2008, researchers found that methylthioninium chloride (MTC) -- a drug that’s been around for about 80 years and has been used to treat urinary tract infections -- seemed to dissolve filaments of tau in neurons, thereby reducing the tangles. Also in 2008, a scientist in Israel discovered AL-108, a drug that apparently prevents the tau protein from exerting its dangerous tangling effect on the brain. And like the vaccines in development to prevent amyloid plaque build-up, these drug therapies need lots more testing – and perhaps tweaking – before they can be made widely, safely available.

In any case, scientific work on these neurofibrillary tangles seems to have momentarily eclipsed the long focus on amyloid plaques as a promising path toward a meaningful response against AD.

Clinical Trials
All drugs – like PBT2, MTC, and AL-108 – must undergo a rigorous clinical trial protocol before the FDA approves them. We often read that a new potential drug is in “phase three.” What do these levels mean? I turned to Wikipedia for this helpful recap:
Clinical trials involving new drugs are commonly classified into four phases. Each phase of the drug approval process is treated as a separate clinical trial. The drug-development process will normally proceed through all four phases over many years. If the drug successfully passes through Phases 1, 2, and 3, it will usually be approved by the national regulatory authority for use in the general population.

Phase 1: Screening for safety
Phase 2: Establishing the testing protocol
Phase 3: Final testing
Phase 4: Postapproval studies

Clinical trials are conducted in phases. The trials at each phase have different purposes and help scientists answer different questions:

In Phase 1 trials, researchers test an experimental drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 trials, the experimental study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 trials, the experimental study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the experimental drug or treatment to be used safely.

In Phase 4 trials, postmarketing studies delineate additional information, including the drug's risks, benefits, and optimal use.
And so, the beat goes on. So far, there is no medical intervention available to prevent or cure Alzheimer's. We can treat symptoms, if temporarily. And -- in the absence of any stunning breakthrough -- it's good that we can do at least that.

So Where Does All This Leave Me?
Frankly, at age 83, I don't expect any major breakthroughs here that will make a difference in my lifetime. And in any event, there's not much I can do except contribute money for the research.

So I focus instead on the studies about simple behavioral changes that might lessen the risk of Alzheimer's. I'll report tomorrow on new studies about the benefits of dietary changes. And I'll keep reminding myself of all the studies that emphasize the benefits of exercise... and maybe even do something about it.

1 comment:

Cindy Dy said...

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