WASHINGTON — A class of monoclonal antibodies that target tau and amyloid beta in Alzheimer’s disease may also recognize proteins in Parkinson’s disease and Lewy body dementia, suggesting to researchers the potential for a broad range of beneficial effects in neurological diseases.
“We have developed monoclonal antibodies that recognize the toxic oligomeric proteins from multiple diseases that cause brain cell death and dementia. This is very promising,” study investigator Fernando Goni, PhD, of New York University School of Medicine, said in a statement. The results were presented at the Alzheimer’s Association International Conference 2015.
Previous research indicated that conformational monoclonal antibodies react to oligomers of amyloid beta and tau in Alzheimer’s disease, as well as to prion disease proteins.
In the present study, Goni and colleagues aimed to determine the binding specificity and capacity of these antibodies and ascertain whether they can be extended to synthetic oligomers of alpha-synuclein and pathological intracellular structures of Lewy body-containing neurons among patients with Parkinson’s disease.
The researchers used electron microscopy and circular dichroism to develop and characterize recombinant alpha-synuclein in monomeric, oligomeric, and fibrillar forms. They then used histologic specimens of formalin-fixed brains from confirmed human cases of Alzheimer’s and Parkinson’s disease for reaction with three anticonformational IgM monoclonal antibodies.
According to study methodology, the monoclonal antibodies were used for immunohistochemical detection on human Parkinson’s disease brain specimens and different alpha-synuclein conformers.
Goni and colleagues reported that after the use of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), IgM monoclonal antibodies exhibited specificity for oligomeric forms of polymerized alpha-synuclein, although not to the monomeric forms. Furthermore, the monoclonal antibodies displayed specific intraneuronal reactivity around the Lewy bodies in human brains from confirmed cases of Parkinson’s disease.
The researchers concluded that monoclonal antibodies that are specific for pathology-associated conformations show promise as immunotherapeutic agents alone or in combination with other approaches in neurodegenerative diseases like Parkinson’s disease.
“We are now at a point where we can test [monoclonal antibodies] in other animal models as a precursor to clinical trials for human neurodegenerative diseases,” Goni said.
Goni F, et al. Abstract #5364. Monoclonal antibodies that recognize oligomeric tau and Aβ, also recognize pathological structures in Parkinson’s disease human brains. Presented at: Alzheimer’s Association International Conference 2015; July 18-23, 2015; Washington, DC.