Alzheimer’s Breakthrough – Part 2

Now imagine the pressure on the physician.

Last week I wrote about the incredibly exciting breakthrough in Alzheimer’s research that was made at the Case Western Reserve University School of Medicine, here in Cleveland. Which is also where I happen to be a professor. Last friday’s issue of the journal Science reported on how Professor Gary Landreth and his team discovered that a cancer drug can quickly reverse Alzheimer’s symptoms in mice. Within 72 hours of administration, the medication halved the number of plaque deposits closely associated with this degenerative brain disease.  Additionally, the signs of cognitive and memory deficits disappeared within that same brief time period.

I rushed to get the news out, but now I want to go a bit more in depth.

Alzheimer’s disease arises in part from the inability to clear amyloid beta from the brain. The new study was motivated by earlier findings by Dr. Landreth, that established the main cholesterol carrier in the brain, ApoE, as facilitating the clearance of amyloid beta proteins. Also, it was demonstrated that people with the ApoE4 gene, who have greatly increased risk of Alzheimer’s disease, have impaired abililty to clear amyloid beta. Combining the findings suggested a possible treatment pathway could be to stimulate ApoE production.

The study used the cancer drug, bexarotene (Targretin), which has been on the market for about 10 years. It increases ApoE in the brain, and, at least in mice, this led to clearance of most of the amyloid beta and dramatic improvements in symptoms.

More encouraging is that bexarotene has a good safety and side-effect profile. Still, it will go through Phase I safety trials to establish safe and therapeutic doses. Knowing an efficacious and safe dose in mice doesn’t easily translate to an efficacious and safe dose in humans.

There are other issues to resolve also. How long can treatment sustain the effect? What dose and how frequent should it be taken? If it does work in humans, does it work in all cases of Alzheimer’s or only the patients with the ApoE4 gene?

In any case, this is a major breakthrough. Not only has a specific drug been identified as a promising new treatment, but perhaps more importantly, a treament pathway has been established. Others may try alternative means of stimulating ApoE production to accomplish the same effect.

Aside from properly controlled trials, there will undoubtedly be real world experimentation. Bexarotene is already on the market, and doubtless there will be off-label prescribing. Think about it. What if your spouse was institutionalized with severe Alzheimer’s disease. You know that doses used in cancer have been relatively safe. Wouldn’t it be more than a little tempting to try it out? Will the doctor be willing? Is it ethical for a spouse to volunteer a demented patient for an off-label treatment?

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Or suppose a person has mild Alzheimer’s and is terrified of the future. If the drug is safe in currently prescribed doses, why not try it?

Read more . . .
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