Introduction

The present invention refers to a monoclonal antibody which specifically binds and neutralizes a neurotoxic tau-derived peptide and its therapeutic application for the cure and treatment of Alzheimer’s Disease.

Technical features

Recent studies show that at least 36.5 million individuals worldwide are affected by Alzheimer’s, but to date no therapeutic agent is available to slow or delay the disease. A crucial pathological feature are intracellular neurofibrillary tangles consisting of the protein beta-amyloid (Aß) and hyperphosphorylated tau. Truncation at the N-terminal tau domain, which thus becomes soluble, plays an important initial role in neurofibrillar aggregation and neurodegeneration that occurs in taupathies such as Alzheimer’s.

The inventors have therefore shown that the intravenous administration of a monoclonal antibody (mAb) 12A12 specific for a portion of the end of the N-terminal domain of tau is able to counteract the early neuropathological and cognitive alterations of subjects affected by human Alzheimer’s and other taupathies. Immunotherapeutic efficacy has been tested in vivo on mouse AD preclinical models. (***p<0.0005 ANOVA analysis of variance  followed by Bonferroni’s, Fisher’s post-hoc test.)

Possible Applications

• Monoclonal antibody for the treatment and/or prevention of oth sporadic and genetic forms of Alzheimer’s Disease;
• Monoclonal antibody for the treatment and/or prevention of not-AD human tauopathies;
• Vaccine.

Advantages

• Selective binding towards a neurotoxic tau-derived peptide linked to Alzheimer’s Disease in two well-established preclinical animal models (Tg2576 and 3xTg) ;
• no cross-reaction toward the physiological full-length tau protein (absence of side-effects due to ”loss-of-function”; toxicity test following long-term immunization in progress).