An “important breakthrough” in Alzheimer’s disease treatment may soon be forthcoming. Local doctor Gerard Nuovo, MD recently published a study revealing encouraging results using an existing drug and mice.
An estimated seven million people in the US suffer from Alzheimer's disease. Although some treatments are available, they are expensive, may slow the disease down a bit, but offer no cure. Some have potentially negative side effects.
The study is considered “pre-clinical” because drugs must be tested in animals before they can be tested in people. Surprisingly, mouse models of Alzheimer's disease are extensively used in research. They are valuable because the mouse brain has the actual human gene that can cause Alzheimer's disease.
In human Alzheimer's disease, certain proteins called “BCL2 family proteins” concentrate in the damaged neurons. A mouse model of the disease involves giving mice the human gene that causes Alzheimer’s then administering a drug to block the BCL2 protein.
The drug, venetoclax, is already approved by the Food and Drug Administration (FDA) and has been thoroughly tested in people. Venetoclax is known to cause few side effects and is often taken by people over 75 years of age with certain types of tumors.
The pre-clinical study used two groups of mice given the human Alzheimer's disease. One group (treated mice) received the drug venetoclax and the other group (untreated mice) received a sham injection. Comparing the mice using venetoclax to their litter-mates found significant results: the untreated mice each had obvious Alzheimer's disease in their first year of life, but their treated litter-mates were fine. At autopsy, the neurons in the central nervous system of the untreated mice were full of the abnormal human protein characteristic of Alzheimer's disease in people. The treated mice showed over 90 percent reduction in the abnormal Alzheimer's disease protein. Importantly, the treatment of the mice started after this abnormal protein had started to form.
Dr. Nuovo stated that the data are encouraging for two reasons: first, the drug worked so well in these mice and second, the drug is already FDA approved for a completely different condition. Dr. Nuovo stressed that the work required the effort of many people without whose help the project could not have been done.
The next key step, he said, is “for other labs to do similar experiments, especially testing the mice after they show signs of Alzheimer's disease, and, of course, to start to do clinical trials in people who have the disease. If the drug works as well in getting rid of the ‘damaged neurons’ in people with Alzheimer's disease as it did in the mice with the human Alzheimer's disease protein, it could well be an important breakthrough for all the people and their families that live with this horrific disease.” Dr. Nuovo stressed that the drug cannot be given now to people with Alzheimer's disease because it must first undergo testing in a clinical trial.
Dr. Nuovo’s study, “Prevention of Fatal Tauopathy in a Mouse Model of Alzheimer Disease by Blocking BCL2,” is published in Applied Immunohistochemistry and Molecular Morphology, a scientific journal indexed in PubMed, the federal repository of scientific research articles (see attached publication). The differences in the treated and untreated mice can be viewed in the attached publication by clicking on the two links on page 5.
