Alzheimer’s: Are we at the beginning of a new era of treatment?

Last Updated on December 30, 2023 by Joseph Gut – thasso

December 29, 2023 – Alzheimer’s disease is a neurodegenerative human disease that occurs in its most common form in people over the age of 65 and is characterized by increasing dementia. It is responsible for approximately 60 percent of the approximately 25 million cases of dementia worldwide. Alzheimer’s disease or Alzheimer’s dementia is often colloquially referred to as “Alzheimer’s”.

There is currently no cure for Alzheimer’s disease. The patients suffer from an increasing formation and deposition of β-amyloid plaques in their brain over time. The only active ingredient that aims to provide a causal therapy for Alzheimer’s disease by binding to the pathological beta-amyloid in the brain is the monoclonal antibody Aducanumab. It received approval from the FDA after more than controversial discussions; the EMA rejected the approval at the time.

The positive effect of the medications currently approved for dementia treatment on existing symptoms is relatively small; they cannot stop the progression of the disease. In 2006, the American Association of Geriatric Psychiatry published a consensus paper on Alzheimer’s treatment. According to a February 2012 preclinical study at Case Western Reserve University, the chemotherapy drug bexarotene was able to dissolve up to 75% of β-amyloid plaques in mice and also reverse symptoms of the disease, such as memory loss. Subsequent preclinical human trials by other research groups failed to confirm the promising results, and so bexarotene was never approved for the treatment of Alzheimer’s disease. For decades there was only frustration and hopelessness in Alzheimer’s research: one drug study after another failed. There was no progress in the treatment of the sick. Whoever received the diagnosis knew that no one could help me anymore.

But now there is finally hope, which could even represent the beginning of a new era in the treatment of Alzheimer’s disease. These are healing or disease-modifying antibodies that are directed against the amyloid beta protein. The latter forms, among other things, the β-amyloid plaques in the brains of Alzheimer’s patients. Although the cause of Alzheimer’s disease remains unknown, advances in understanding amyloid pathology have revealed a possible link between the amount of amyloid plaques deposited in the brain and the development of Alzheimer’s disease.

One of the two antibodies in question, Lecanemab, marketed under the name Leqembi, is a monoclonal anti-amyloid beta antibody. Lecanemab received accelerated approval for medical use in the United States in January 2023 and in July 2023 was fully approved by the FDA. It is administered via an intravenous infusion and its most common side effects include , infusion-related reactions and amyloid-related image disturbances, a side effect known to occur with the class of antibodies directed against amyloid.

The second of these antibodies, Donanemab (also known as N3pG), is an antibody produced in mice that also targets the abnormal amyloid beta (Aβ) protein. It is currently in Phase III clinical trials to determine whether it slows the progression of early Alzheimer’s disease. The results achieved are of great importance because there is currently no known cure or disease-modifying treatment for Alzheimer’s disease other than Lecanemab. Donanemab has shown positive results in its early clinical trials and is considered a promising potential treatment for Alzheimer’s disease alongside Lecanemab. It was found that patients who received Donanemab slowed the worsening of their disease by an of 22 percent. In patients who took the drug at an early stage of the disease, the figure was even up to 60 percent.

These therapies, which are expected to receive approval in additional countries outside the United States in the new year, offer real hope for Alzheimer’s patients and their treating physicians. This is an absolute milestone because it involves a completely new approach. What we are seeing here is a whole new generation of drugs that specifically attack a suspected molecular mechanism for the development of Alzheimer’s disease (i.e.,  “targeted medicine”). The effect on the progression of symptoms is still limited, but over 100 of such drugs are now in development based on the concept behind Lecanemab and Donanemab. This is the beginning of a new era in Alzheimer’s therapy.

Thasso has previously discussed some aspects of Alzheimer’s disease, it’s genetics and it’s ethnic risk differences in a couple of posts such as in A), B), C), and D).

Here are a few words about Alzheimer’s disease and the outlook for effective new medications and ways of new theraphies:

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