Alzheimer’s: New Experimental Treatment May Postpone Symptom Onset

Alzheimer's disease remains incurable to date. However, research efforts have resulted in drug treatments to slow down and decrease symptoms. The most recent targets one of the causes of the disease directly: amyloid plates. The Gentenumab is one of them. Despite mixed preliminary results, he was the subject of an open extension study, aimed at assessing his tolerance and long -term effectiveness. He could ultimately delay the appearance of the disease for several years.

The first treatments offered to people with Alzheimer's disease essentially aimed at treating symptoms. These drugs (Galantamine, Donépézil, Rivastigmine, etc.) prevent the degradation of acetylcholine – a neurotransmitter involved in memory and learning. They thus make it possible to slow down cognitive decline and reduce behavioral disorders. Despite significant results, these drugs have serious side effects and are therefore no longer reimbursed by health insurance.

Immunotherapy is today one of the most promising tracks to develop new treatments. The elimination of amyloid plaques by therapies based on monoclonal antibodies – such as leccanémab, marketed in Europe since November 2024 – has slowed the clinical progression of symptomatic Alzheimer's disease. However, it is not known whether it is possible to delay the appearance of clinical symptoms in predisposed people who do not yet have signs of the disease.

A study on hereditary forms of the disease

Alzheimer's disease is most often sporadic. In other words, it occurs in a “random” way, resulting from a set of genetic and socio-environmental factors. Contrary to popular belief, the hereditary form of the disease is much rarer (less than 1% of cases). It occurs much earlier, before 65 years, even before 50 years. This dominant autosomal family form results from a mutation on one of the genes that we know associated with the disease (App, PSEN1, PSEN2). A genetic test makes it possible to determine if the transferred gene has been transmitted.

There Dominantly inherited Alzheimer Network Trials Unit (Dian-tu) is a unit launched in 2012, responsible for assessing the safety and efficiency of several experimental treatments in participants carrying one of the genetic mutations mentioned above. These patients were necessarily asymptomatic or with light cognitive impairment. Among the treatments tested: the Gantenumab, developed by the Roche group. Like leccanab, it targets the beta-amyloid peptide, which it eliminates by phagocytosis.

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The very first Dian-Tu study, conducted from 2012 to 2019, then phase 3 trials, controlled by placebo, showed that the Gantenumab reduced amyloid plates in people with Alzheimer's disease at an early stage. The observed effect was dependent on the dose. On the other hand, the drug did not significantly slow down the cognitive decline in relation to the placebo.

These results led to an “open extension study”, lasting 3 years. It aimed to assess the safety and efficiency of long -term treatment. In particular, it was a question of determining whether higher doses of ganénumab could completely eliminate amyloid plates and thus delay the clinical progression of the disease.

A risk of symptoms reduced by half!

The study was conducted in 18 sites in Australia, Canada, France, Ireland, Puerto Rico, Spain, the United Kingdom and the United States. All the participants came from the previous clinical trial. They had therefore already received Gentenumab or a placebo, and knew their status of genetic mutation. The researchers examined the effects of increasing doses of Ganénumab, up to 1500 mg every 2 weeks. This time, there was no placebo control group. The results have just appeared in The Lancet Neurology.

A total of 73 people received Ganénérumab as part of this extension study. Only 13 of them finished the three years of treatment. Thirteen others left the study prematurely due to undesirable effects or a progression of their illness. Finally, 47 participants finally withdrew due to the premature judgment of the study by the promoter. Indeed, in 2023, Roche interrupted the development of its product after disappointing results. The rate of elimination of beta-amyloid was lower than expectations.

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The primary analysis, which was to focus on eliminating amyloid plates, included 55 participants (some of whom had stopped treatment prematurely). Among them, 22 people received gentenumab both during the first clinical trial and during the extension of the study, for an average of eight years. For these patients, the risk of developing symptoms was divided by two!

There was no serious hemorrhages or deaths associated with treatment. On the other hand, Aria (Amyloid Related Imaging Abnormalitiesanomalies visible to MRI, which result from product activity) and micro-hemorrhages have been observed in almost half of the 73 participants.

Several biases, but promising results

“” Partial or short -term elimination of the amyloid has no significant clinical effects. However, the complete long -term amyloid elimination has potentially delayed the appearance of symptoms and the increase in dementia “, Conclude the authors of the study. They believe that if patients start the treatment early enough, for a fairly long period, they could be preserved from the disease, perhaps for years.

However, these results must be interpreted with caution, because this study did not involve a control group. In addition, people who abandoned the phase 3 study were not eligible for the extension of the study, which means that the participants retained had to be in relatively good health and be better from the start.

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However, the results are promising. “” These are the first data suggesting that there is a significant delay possibility in the appearance of the progression of symptoms “Said Dr. Eric McDade, professor of neurology at the University of Washington in Saint-Louis and co-author of the study, to CNN.

A promising track threatened by a lack of funding

Sue, a 61 -year -old participant, is part of the L'Esta Genénumab group since 2012. She joined the study shortly after discovering that she was carrying a genetic mutation that would cause early Alzheimer's disease. Two of his brothers, also carrying the mutant gene, also participated in the trial, but started treatment after developing symptoms around 57 years old. Sue, she does not present at the moment. She really thinks that treatment has delayed the appearance of the disease.

Marty Reiswig, from Denver, is also one of the participants. He has a mutation in the PSEN2 gene. Family members carrying this mutation begin to have symptoms between 47 and 50 years old. His father died in 2019, at the age of 66. Marty is 46 years old. He started in the Solanezumab group of the study, then went to the Gentenumab in the extension. He has not noted any symptoms for the moment.

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The research team is now concerned about the study. A possible subsidy refusal on the part of National Institutes of Health could soon end its funding. Patients under Genénérumab for years may no longer have access to their medication. They will then have to turn to the currently approved treatments.

This turnaround would be a great loss, both for scientists and for patients. “” Continue to follow them under treatment can constitute the best possible test of the amyloid hypothesis and provide decisive evidence, For or against this hypothesis. The continuation of the financing of this study should be an absolute priority “Said Dr. Michael Greeicius, professor of neurology and neurological sciences at the University of Stanford, who did not participate in the study.

“” Personally, it terrifies me. I will be removed from me a drug that saves my life and I will be let the first symptoms wait to start slowing down the disease with Kisunla [ndlr : donanemab] or leqembi [ndlr : lécanémab] “Said Marty to CNN.