The potential of intracellular antibodies for therapeutic targeting of protein-misfolding diseases

Misfolding diseases are a wide group of devastating disorders characterized by the accumulation of pathological protein aggregates. Although these disorders still lack an effective treatment, new antibody-based strategies are emerging and entering clinical trials. The intrabody approach is a gene-based technology developed to neutralize or modify the function of intracellular and extracellular target antigens. Because intrabodies can potentially target all the different isoforms of a misfolding-prone protein, including pathological conformations, they are emerging as therapeutic molecules for the treatment of misfolding diseases, including Alzheimer's, Parkinson's, Huntington's and prion diseases. This review will provide a description of the intrabody approach, an update of preclinical studies on misfolding diseases and an outlook on the intrabody delivery issue for therapeutic purposes.