The active Alzheimer’s Disease (AD) pipeline is populated with 583 products, with a highly diverse range of molecular targets. GBI Research analysis revealed a high degree of innovation in this indication, with 46% of the pipeline being first-in-class products, acting on over 40 first-in-class molecular targets. In addition, the pipeline is characterized by the strong presence of therapies that target multiple components implicated in the amyloid cascade, several molecular targets of which are known to trigger familial AD.
Given that the currently approved therapies for AD are limited to acetylcholinesterase inhibitors and glutamate receptor antagonists, the pipeline offers a broad range of treatment options that may possess disease-modifying properties. However, evaluation of the Preclinical and clinical evidence for their therapeutic potential reveals that the novelty of the molecular target is not sufficient to effectively reduce the rate of AD progression in human patients.
Programs undergoing Preclinical development exhibit diverse disease-modifying mechanisms of action, and many represent strong alternatives to targets with a direct role in the amyloid and tau processes due to their roles in promoting neuronal survival and plasticity, a process critical to memory and cognition. Brain-Derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) are considered promising targets in AD, primarily due to their potency in exhibiting significant neuroprotective effects in Preclinical studies.
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Members of the caspase-mediated apoptotic cascade also show therapeutic potential, as early investigations have revealed an ability to modulate molecular mechanisms underlying synaptic plasticity in animal models, which translates into amelioration of behavioral deficits. Thus, growing insights into disease-causing processes in AD are being translated into a growing population of innovative therapeutic targets, as reflected in the highly innovative pipeline.
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