Research

Specific Targeting of Aβ Toxins (“Oligomers”)

Alzinova’s mission is to bring true disease-modifying therapy and diagnostics to Alzheimer’s disease patients. By using the proprietary AβCC technology, Alzinova can develop a theragnostic that is unique in that it targets/detects Alzheimer’s disease-driving toxins of Aβ (“oligomers”) specifically.

Several preclinical studies in transgenic mice, as well as clinical investigations on human subjects, support using immunotherapy for the treatment of Alzheimer’s disease. Clinical efficacy is, however, more or less lacking. This is likely due to very low specificity for the toxic oligomers, as the tested substances target virtually all forms of Aβ.

Alzinova’s lead candidate vaccine ALZ-101, and the monoclonal antibody ALZ-201, are both designed to minimize redundant cross-reactivity with generic Aβ, to provide increased specificity towards toxic oligomers.

 
Vaccine ALZ-101

ALZ-101 is a vaccine for Alzheimer’s disease designed to induce a humoral antibody response capable of reaching the toxins (the “oligomers”) in the brain and thereby protecting brain synapses from Aβ-induced damage. Preclinical studies in a transgenic mouse model demonstrated a 25% increase in synaptic density in treated mice versus controls, in accord with the view that Alzheimer’s disease primarily is a synaptic dysfunction caused by soluble Aβ oligomers. The unprecendented specificity for the target was demonstrated by the fact that the conspiquous insoluble deposits of Aβ (the “plaques”), which are present already at the non-clinical Alzheimer’s disease stage (“stage 1”) and in many healthy individuals, were not targeted in these mice. True oligomer-specific therapies are rare, and have never been evaluated in human subjects.

ALZ-101 is now set for preclincal deveopment in preparation for Phase 1/2a clinical trials.

Development of ALZ-101 was supported by the Eurostars Programme (project E!7927 AD-AIM) during 2013 – 2015. The program has recently received support from the Swedish innovation agency VINNOVA.

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Monoclonal Antibody ALZ-201

The murine monoclonal antibody ALZ-201 (of IgG isotype) was produced and selected using the AβCC technology. It exhibits extremely high oligomer specificity, and does not react with functional (nonaggregated) or inert (fibrillar) Aβ. Further, it does not cross-react with any Aβ40. It is now being validated as a highly selective primary antibody in assays aiming to detect toxic oligomers in CSF for diagnostic purposes.