Immunotherapy for Alzheimer’s Disease: Current Scenario and Future Perspectives

Abstract

Alzheimer’s disease (AD) is a global health concern owing to its complexity, which often poses a great challenge to the development of therapeutic approaches. No single theory has yet accounted for the various risk factors leading to the pathological and clinical manifestations of dementia-type AD. Therefore, treatment options targeting various molecules involved in the pathogenesis of the disease have been unsuccessful. However, the exploration of various immunotherapeutic avenues revitalizes hope after decades of disappointment. The hallmark of a good immunotherapeutic candidate is not only to remove amyloid plaques but also to slow cognitive decline. In line with this, both active and passive immunotherapy have shown success and limitations. Recent approval of aducanumab for the treatment of AD demonstrates how close passive immunotherapy is to being successful. However, several major bottlenecks still need to be resolved. This review outlines recent successes and challenges in the pursuit of an AD vaccine.

Clinical outcome measures in dementia with Lewy bodies trials: critique and recommendations

“…Currently, symptomatic therapies are limited in DLB and there are no disease-modifying therapies (DMTs). However, disease-modifying approaches are being strongly pursued in other neurodegenerative conditions, for example, amyloid beta-directed monoclonal antibodies for AD and genetic therapies targeting glucocerebrosidase mutations in Parkinson’s disease (PD) [ 3 , 4 ]. Therefore, establishing robust outcome measures is crucial to permit the evaluation of symptomatic treatments and DMTs in DLB.…”

A novel bio-inspired strategy to prevent amyloidogenesis and synaptic damage in Alzheimer’s disease

“…Recently, one anti-amyloid antibody (aducanumab) was approved under the accelerated approval pathway by FDA as new disease-modifying compound in AD. However, there is still uncertainty about the real efficacy and safety of aducanumab, even taking into account the previous attempts with other monoclonal antibodies, and both academic institutions and pharmaceutical companies are actively in search of innovative treatments [34,35]. The reasons for the glaring failure of the therapeutic strategies against AD are most likely multiple and include, among others, (i) the rationale of the therapeutic approaches that in some cases are based on theoretical assumptions or-even if validated in animal models Fig.…”

“…Recently, one anti-amyloid antibody (aducanumab) was approved under the accelerated approval pathway by FDA as new disease-modifying compound in AD. However, there is still uncertainty about the real efficacy and safety of aducanumab, even taking into account the previous attempts with other monoclonal antibodies, and both academic institutions and pharmaceutical companies are actively in search of innovative treatments [ 34 , 35 ]. The reasons for the glaring failure of the therapeutic strategies against AD are most likely multiple and include, among others, (i) the rationale of the therapeutic approaches that in some cases are based on theoretical assumptions or—even if validated in animal models—are too weak to go all the way down the bench-to-bedside route [ 36 , 37 ], (ii) the timing of therapeutic intervention—which should be very early along the natural history of the disease—(iii) the phenotypic variability of AD [ 38 ]—that deeply affects and diversifies the responsiveness to treatments—and (iv) the complexity of disease pathogenesis suggesting that more than one target should be locked by therapeutic strategies to be successful in tackling the illness [ 7 , 39 , 40 ].…”

A novel bio-inspired strategy to prevent amyloidogenesis and synaptic damage in Alzheimer’s disease

“…Recently, one anti-amyloid antibody (aducanumab) was approved under the accelerated approval pathway by FDA as new disease-modifying compound in AD. However, there is still uncertainty about the real e cacy and safety of aducanumab, even taking into account the previous attempts with other monoclonal antibodies, and both academic institutions and pharmaceutical companies are actively in search of innovative treatments [34,35]. The reasons for the glaring failure of the therapeutic strategies against AD are most likely multiple and include, among others, (i) the rationale of the therapeutic approaches -almost exclusively based on theoretical assumptions or in vitro evidence [36, 37] -(ii) the timing of therapeutic intervention -which should be very early along the natural history of the disease -(iii) the phenotypic variability of AD [38]that deeply affects and diversi es the responsiveness to treatments -and (iv) the complexity of disease pathogenesis suggesting that more than one target should be locked by therapeutic strategies to be successful in tackling the illness [7,39,40].…”