Lloyd Tran, PhD, Biomed Industries, Inc., San Jose, CA, shares an update on the neurogenesis hypothesis of Alzheimer’s disease (AD) and the clinical development of NA-831, an oral small molecule developed to boost adult hippocampal neurogenesis and neuroprotection for the treatment of AD. Doublecortin-expressing (DCX+) neuronal progenitors are shown to be markedly decreased in patients with AD compared to controls, impairing adult hippocampal neurogenesis. This impairment appears to take place prior to the development of amyloid and tau pathology, implicating it as a valuable early target for intervention. NA-831 was developed on this basis and new evidence on its mechanism of action has shown that it increases DCX+PCNA+ cell levels, acting as a catalyst to restore neurogenesis. In a Phase IIa study of patients with mild cognitive impairment (MCI) and mild-moderate AD, NA-831 was shown to elicit significant improvements in ADAS-Cog-13 scores after 24 weeks, compared to placebo. Further trials are now being planned, including a Phase III trial of almost 500 patients with mild-moderate AD, as well as a prevention trial in 585 asymptomatic individuals. Dr Tran notes that once the neuropathological hallmarks of disease have started to accumulate, it may be too late to prevent or reverse the damage, but by boosting neurogenesis prior to pathology development, we may be able to preserve cognitive function and promote synaptic resilience. This interview took place at the AD/PD™ 2023 congress in Gothenburg, Sweden.
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