Development of a highly promising drug candidate for delaying the progression of Alzheimer’s disease

Alzheimer's diseaseaffects 44 million people worldwide today, and the number of affected individuals is expected to triple by the year 2050, resulting in staggering financial, societal, and emotional costs. Currently, there is no effective therapy for the treatment of AD. Thus, effective treatments or preventive interventions for AD are extremely needed. The multifactorial nature of AD emphasizes the need for drug candidates that simultaneously address several therapeutic targets. We have synthesized and developed a biocompatible, water-soluble, chemically- and metabolically-stable, highly potent neuro-protectant – SSA37. This drug candidate is capable of simultaneously dissolution of Aβ oligomers/aggregates, inhibition of Aβ oligomerization, acting as anti-oxidant, and protection of neurons from AD insults. It rescued primary neurons from oxidative stress and Aβ42 toxicity and turned the behavior of AD-model animals (5XFAD), as well as their learning and spatial memory back to tha

t of wild type animals. The mechanism of neuro-protection of SSA37 involves P2Y-receptors activation, Fe(II) chelation, and Aβ42 solubilization. It is noteworthy that our study involved a highly aggressive AD mice model and a preventive protocol, namely, AD mice were treated for several weeks, while the behavioral studies were performed 1-3 months after treatment was completed. Since AD develops ca. 20 years before diagnosis, the significance of the preventive potential of SSA37 is immense.

Identification of Highly Promising Anti-Oxidants / Neuroprotectants Based on Nucleoside Phosphorothioate Scaffold. Synthesis, Activity, and Mechanisms of Action. Sagit Azran, O. Danino, D. Forster, S. Kenigsberg, G. Reiser and B. Fischer. J. Med. Chem. 2015, 58, 8427−8443.

A promising multifunctional biocompatible drug candidate for delaying the progression of Alzheimer’s disease. H. Segal-Gavish, O. Shimon, D. Offen, and B. Fischer. Journal of Alzheimer's Disease. 2017, 58 (2), 289-301.