New treatments against Alzheimer’s dementia: the eye of the face – 07/08/2023 – Luciano Melo

I have a friend who believes that there are Bolshevik red blood cells in Vladimir Putin’s veins and that in the dictator’s thalamos the neurotransmitters are Leninist emojis.

With some difficulty in assimilating the fall of a wall in 1989, he thinks that Fidel Castro and his shadow, Maduro, are more like Karl Marx than Fulgêncio Batista. As he scratches his scruffy beard, he indulges in a thought that is, finally, universal. He fears suffering from Alzheimer’s disease in the future, the fate that marked the end of his parents. But he is excited. He found out about a new, very good medicine against the disease. Knowing that I’m a neurologist, he came to ask me if it’s good to anticipate and use the novelty, just to be sure. One person participating in the conversation commented that there is an equivalent to planning chemotherapy to treat a cancer that may appear in 20 years.

It’s not exactly a new medicine. The novelty is broader, it appears in a class of drugs. These have mab at the end of the name, a suffix that indicates the presence of a single-lineage antibody. Modified by biotechnology, the component of our defenses becomes a precise drug, like certain missiles capable of hitting, without fail, difficult targets. For some decades, mabs have been used to control several diseases, such as neoplasms, autoimmune diseases and headaches. In Alzheimer’s disease, the aim is to reach an abnormal protein lump, called β-amyloid, which adheres to the surface of brain neurons.

These aggregates were identified as one of the causes of brain cell death, the engine of degeneration caused by the disease. The new class of drugs clears the brain of this unwanted occupant. By demonstrating efficacy, they confirm the supposed deleterious effect of β-amyloid.

All of this so that pharmaceutical giants, allied with funding from the US government, meet our desire for a longer healthy life, at least intellectually healthy. We will finally be able to spend longer, in old age, the finances that we managed to accumulate in youth. There is an eldorado covered in dollars awaiting the manufacturer who created the best chemical to stop dementia. And possibly a Nobel Prize awaits the scientist of the first experiences, who paved the way that will bring, what we will have.

The first contender for glory was the drug aducanumab, but it didn’t come close. In June 2021, the United States health regulatory agency (FDA) granted approval, somewhat accelerated, to this drug, the first to a mab against β-amyloid. The action was considered untimely, since the alleged therapeutic effect, if any, is modest, and not free of having unwanted consequences.

All these disadvantages under annual costs of $56,000. At that price, a massive prescription would wipe out health funders. Just as access to the best medical practices would continue to separate, by an impermeable line, those who rule from those who obey. After aducanumab, results from other drugs followed, launching complicated names like donanemab, lecanemab, solanezumab, gantenerumab. All tested on people with early symptoms of Alzheimer’s disease. However, only donanemab and lecanemab demonstrated efficacy. Under pressure from competitors, the price of aducanumab has dropped considerably, obviously far from becoming a bargain.

I will not concentrate on comparing the actions of new drugs, however, at your disposal, I leave the references for you, the reader, to make your judgments. Know, however, that no new drug stopped the cognitive decline or brought recovery of lost abilities. Successful compounds have only reduced the progressive worsening and remain especially expensive.

Anyone who is concerned about finances can quantify their afflictions through a metric, which in simplified analysis monetizes life, cost-effectiveness. It’s a way of assessing whether the medication is worth what it weighs. And to calculate the financial return of an investment in health. My Stalinist-post-modern-anti-American friend has an aversion to this facet of capital. For him, the only important measure should be employed to quantify well-being. However, the importance of cost-effectiveness is undeniable, especially for an astronomical budget that will be committed to extending the trajectory of many, for another handful of years.

US health care costs for people with Alzheimer’s disease, however, are already titanic. In 2021, it was about US$ 355 billion, estimates estimate that it could exceed US$ 1 trillion by 2050. The therapy will be cost-effective if it reduces these values, by reducing expenses with other treatments, care, social security demands, and increasing the time someone contributes to the tax. Doctors at Massachusetts General Hospital in Boston calculated that neither aducanumbab (with discounts) nor donanemab are cost-effective. For someone who holds the key to the vaults, effectiveness is not enough.

We know that β-amyloid plaques accumulate in brains before symptoms begin. So it’s possible that my friend, you and I already have this lump inside our skulls and we innocently await the inevitable consequence that will arrive in decades. Possibly some group of scientists will prove that, in this case, if we receive some mab before any clinical signs of disease, we will be free of Alzheimer’s disease. And then, at very low prices, my friend will be able to adopt the prevention he already dreamed of, at the risk of side effects. And you?

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