Alzinova‘s ALZ-101 vaccine — designed to target toxic forms of the amyloid beta protein that drive neurodegeneration in Alzheimer’s disease — was well-tolerated in non-human primates and displayed efficacy in a fish model of the disease.
A clinical study in patients with early Alzheimer’s disease now is expected to start later this year.
Results of the study, “Oligomer-specific Active Vaccine Approach for the Treatment of Alzheimer’s Disease,” will be presented today by Anders Sandberg, PhD, chief scientific officer at Alzinova, during the 14th International Conference on Alzheimer’s and Parkinson’s Diseases and related disorders, running from March 26-31, Lisbon, Portugal.
Alzheimer’s disease develops as a consequence of deposits of toxic clumps of mutant forms of amyloid beta protein in the brain. There are different forms of amyloid beta, however, the toxic form that promotes nerve cell death and neurodegeneration is its oligomer form — when several single units (monomers) of the protein aggregate.
Recent preclinical studies suggests that within amyloid beta oligomers, only a small subset carries full neurotoxic potential. These findings challenge the concept that developing therapeutics specific for amyloid beta oligomers will provide an efficient approach.
Researchers at Alzinova used AβCC peptide technology to isolate large fractions of Aβ42 oligomers, whose accumulation in the brain was identified as a determinant event triggering Alzheimer’s disease progression. The team used Aβ42 oligomers as a template to produce a specific vaccine against it, called ALZ-101.
Preclinical studies using a mouse model of Alzheimer’s disease showed that treatment with ALZ-101 led to a 25% increase in the number of synapses — the junctions between two nerve cells that allow them to communicate — in the brain of treated animals compared to controls (untreated).
For this study, researchers tested ALZ-101’s characteristics — specificity, safety, tolerability and its capacity to induce an immune response against amyloid beta oligomers — in non-human primates. The vaccine’s effectiveness also was assessed in freshwater zebrafish, which has been recognized as a suitable model to study various stages of Alzheimer’s.
Zebrafish were challenged with toxic human brain extracts, and researchers assessed the vaccine’s ability to rescue zebrafish embryos’ startle response. This is a rapid, generalized extreme response to a sudden, surprise stimulus and has been used as a readout for motor function, sensory physiology and basic forms of learning.
The results showed the vaccine was well-tolerated in non-human primates, with no signs of toxicity or inflammation. Moreover, despite targeting only a small fraction of amyloid-beta oligomers, the vaccine improved the ability of zebrafish embryos to learn the startle response after being challenged with toxic human brain extracts.
Overall, these findings suggest that “ALZ-101 is well suited as a long-term treatment option for preclinical and prodromal Alzheimer’s disease to prevent or delay the onset of dementia,” researchers wrote.
“A double-blind, randomized, parallel-group multiple dose study on the safety, tolerability and immunogenicity of ALZ-101 in patients with early Alzheimer’s disease is set to start in 2019,” they added.
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