Cienciaes.com: Alzheimer. | Science Podcast

2021-06-17 12:13:23

We are going today, as usual, to go back twenty years in the past. At that time it was the first time he had broached the subject of a terrible disease for which there was no cure: Alzheimer’s disease. What was already known about that disease then? Has there been any significant progress to improve its treatment or to prevent it?

This is how he described in an informative way what was known about Alzheimer’s disease twenty years ago:
Cure for Alzheimer’s?

How is the situation today regarding the treatment of Alzheimer’s?

Let’s start by explaining better the operation of the drugs that I mentioned then.
Tacrine is a cholinesterase inhibitor, which destroys acetylcholine, which increases the amount of this neurotransmitter in the nervous system, as it is destroyed at a slower speed thanks to the slowing effect of this destruction exerted by tacrine. Tacrine has been abandoned in at least the US since 2013. It appears that tacrine did not offer benefits outweighing risks.

The drug donezepil seems to improve cognitive abilities somewhat, but it does not stop the development of the disease. It continues to be prescribed to treat Alzheimer’s, although it is more of a palliative than a cure. Donezepil is also a cholinesterase enzyme inhibitor, and therefore increases the concentration of the neurotransmitter acetylcholine, which seems to improve some cognitive abilities and memory.

Rivastigmine is another inhibitor of acetylcholine destruction. In this case, the inhibition is more potent than in the case of donezepil, because this drug simultaneously inhibits two enzymes involved in the destruction of acetylcholine, and not just one, as donezepil does. Rivastigmine is able to cross the blood-brain barrier more effectively than the other two drugs. It also has better pharmacodynamic properties than these, and it is broken down more gently, we could say, than the other drugs. This increased efficacy of rivastigmine also increases the severity of the side effects of all of these drugs that act on acetylcholine breakdown, including nausea, vomiting, and diarrhea.

There is yet another cholinesterase inhibitor drug, which is galantamine. This is an alkaloid, that is, a natural product produced by some plant species, although today it can be produced by chemical synthesis.

What happened to clioquinol? This medication is an antifungal, that is, it is used against fungal infections, but some data indicates that it could act as a protector against the neurodegeneration of Huntington’s and Alzheimer’s diseases. However, its use to treat Alzheimer’s has not been approved.

About three years ago, the use of an extract of the Ginkgo biloba tree for the treatment of Alzheimer’s was authorized in Europe, although clinical evidence does not indicate that its efficacy is superior to that of the cholinesterase inhibitors mentioned above. Ginkgo biloba is a tree native to China and the only survivor of the order of plants called Ginkgoales, which appeared 290 million years ago.

What has happened to the vaccine? From what I have been able to ascertain, the vaccine was intended to generate antibodies that count the amyloid beta protein. Antibodies should be generated by immunizing with that protein as the antigen. A series of serious side effects prevented the development of this type of vaccine.

Fortunately, a vaccine-like treatment for Alzheimer’s has just been approved this month, June 2021. It is a monoclonal antibody called Aducanumab. The idea of this treatment is that instead of the body itself producing antibodies, these are produced abroad and administered to patients. In this way, the side effects of vaccines are avoided.
A parenthesis to indicate that all the treatments ending in “mab” are monoclonal antibodies, that is, produced by a clone of B lymphocytes that produce only one antibody. Based on the letters immediately before “mab”, we can tell its origin. Thus, the letter “u” before “mab” indicates that the antibody is human. This means that the protein will not be rejected by the immune system, since the human being will not be identified as foreign by it.

Monoclonal antibodies, like the antigens used in vaccines and other large molecules of biological origin, are not strictly speaking drugs, they are biological products. Drugs are generally small molecules that can be purified by physical-chemical means, or synthesized from simpler molecules by chemical procedures. Antibodies, vaccines, protein hormones, such as insulin, etc., should be called by another term, which could well be biopharmaceuticals. A biopharmaceutical would be that therapeutic molecule that needs to be produced from the activity of living cells. Thus, monoclonal antibodies would be biopharmaceuticals because they are produced in cultured mammalian cells, plants, insects or even in bacteria infected with bacteriophage viruses. They cannot be produced synthetically.

Aducanumab is a monoclonal antibody whose antigen is aggregated beta amyloid protein. It is the first Alzheimer’s treatment approved in the US since the 2000s.
The antibody is able to cross the blood-brain barrier and act directly by binding to the aggregated amyloid beta protein. This destroys the plaques formed by it and decreases its neurotoxicity, thus slowing down the progression of the disease.

Aducanumab has been approved in the US this month, as I was saying, but its approval is not without controversy, because its efficacy does not seem to be high enough and some experts indicate that the studies have not shown enough evidence to confirm that Aducanumab works as the company that produces it, Biogen, maintains that it does.

As we can see, Alzheimer’s disease is far from being cured. However, it is possible to prevent it to a greater or lesser degree. Regular physical exercise is the best way to keep your brain in good shape. Continuing to learn and educate ourselves throughout life, as you are doing listening to these programs and I am doing them, is a proven way to prevent cognitive decline. I hope these tips get us to live a better life.

Jorge Laborda (06/17/2021)

Works by Jorge Laborda.

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