Therapeutic news in Alzheimer’s disease: soon a disease-modifying therapy?

Abstract

Research on disease-modifying treatments for Alzheimer’s disease has resulted in a series of failures over the past 20 years. However, in the last 4 years, five molecules have shown significant effects in phase II or III trials on clinical endpoints (i.e., slowing of cognitive decline). Among these five molecules, three are anti-amyloid immunotherapies: aducanumab, donanemab, and lecanemab responsible for a significant clearance of cerebral amyloid deposits. These results are still awaiting confirmation in order to put an end to the controversy surrounding the Food and Drug Administration’s decision to give conditional approval to aducanumab, which is considered premature by many specialists. Confirmation is also necessary to assess the benefit (magnitude of the slowing of decline) and risk (edema and cerebral hemorrhage induced by these treatments) balance of these molecules, which appears to be so far questionable after 18 months. Masitinib, a treatment whose probable mechanism of action is neuroinflammation, has also shown positive effects that need to be confirmed. Treatments targeting the tau protein are less advanced but weak signals are emerging from immunotherapies in the moderate stages of the disease (semorinemab). There is renewed hope for patients since it may not be unreasonable that these disease-modifying therapies will be part of the French therapeutic arsenal within the next five years.