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 three years, four molecules have shown significant effects on clinical endpoints in phase II or III clinical trials (i.e., slowing of cognitive decline). Among these four molecules, three are anti-amyloid immunotherapies: aducanumab, donanemab, and lecanemab, responsible for a significant clearance of cerebral beta-amyloid deposits. These provisional data are still awaiting confirmation to put an end to the controversy surrounding the 2021 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 cognitive decline) and risk (edema and cerebral hemorrhage induced by these treatments) balance of these molecules. Masitinib, a treatment whose probable mechanism of action is neuroinflammation, has also shown positive effects that need to be confirmed. Therapies targeting the tau protein are less advanced and have yet to be proven. Patients have renewed hope since it may not be unreasonable that these disease-modifying therapies will be part of the French therapeutic arsenal within the next five years.