This opens a new approach to diagnose and evaluate the effectiveness of treatments for these neurodegenerative diseases.
It is widely accepted that misfolded amyloidogenic proteins, alpha-synuclein, mutant Huntington protein, and amyloid-beta, are toxic species that play a role in the development of neurodegenerative diseases including Parkinson’s, Huntington’s, and Alzheimer’s diseases.
However, there are currently no conclusive diagnoses for the early stages of these neurodegenerative diseases.
Despite the differences in the makeup of amyloidogenic proteins and their associated diseases, these misfolded aggregates assembled from distinct amyloid proteins share general common structural features and mechanisms of toxicity. Therefore, antibodies targeting each specific misfolded amyloidogenic protein can be powerful tools for early diagnosis and treatment of several neurodegenerative diseases.
Over the past decade, molecular imaging — the visualization, characterization, and measurement of biological processes at the level of cells and molecules in humans and other living systems — has become a thriving field and offers potential tools for disease diagnosis.
Magnetic resonance imaging (MRI) techniques represent one of the best non-invasive molecular imaging methods and hold great promise for studying the brain.
The use of nanoparticles — tiny molecules — also is attracting increased attention due to their unique capacity to facilitate diagnostics and therapeutics. Among all types of nanoparticles, biocompatible superparamagnetic iron oxide nanoparticles (SPIONs) have attracted a great deal of attention for therapeutic delivery applications.
SPIONs consist of magnetic cores made of iron oxides coated with a biocompatible polymer that can be targeted to the required area through external magnets. The coating acts to shield the magnetic particle from the surrounding environment and also can be used to attach different types of molecules to increase their targeting capacity. These molecules then act as attachment points for the coupling of therapeutic molecules or antibodies to be delivered to the organ of interest.
SPIONs have been shown to penetrate the blood-brain barrier — a lining of cells that protect the brain from circulating molecules capable of damaging and disrupting neural function. When joined with an antibody that recognized amyloid-beta, SPIONs were successfully used to diagnose Alzheimer’s using MRI.
Although recent advances in molecular imaging techniques have improved the ability to diagnose other neurodegenerative diseases, Parkinson’s is still diagnosed mainly by a doctor’s observation based on motor symptoms including slowness of movement (i.e., bradykinesia), resting tremors, and muscular rigidity. For these reasons, researchers wanted to investigate whether SPIONs could be used to target amyloidogenic proteins in Parkinson’s disease and Huntington’s disease.
The team developed an amyloidogenic-targeted molecular MRI probe called W20-SPIONs. This imaging probe consists of an amyloidogenic-specific antibody known as W20 joined to SPIONs.
The researchers showed that these W20-SPIONs were stable, non-toxic, and specifically recognized alpha-synuclein oligomers in human cells and mice. Oligomers consist of a few units (or monomers) and are suggested to be the most toxic form of amyloid.
When applied to mouse models of Parkinson’s and Huntington’s, W20-SPIONs crossed the blood-brain barrier and specifically bound to the brain regions with amyloidogenic proteins, giving an MRI signal and distinguishing between mice with neurodegenerative disease from healthy controls.
These results indicate that W20-SPIONs have potential in early-stage diagnosis of Parkinson’s and Huntington’s disease and open a new strategy for assessing the effectiveness of new treatments for neurodegenerative diseases.
“In our study, W20-SPIONs showed sufficient signal sensitivity, good biostability, and no potential toxicity in vitro and in vivo, which also had the capacity of specially targeting oligomers in the brain,” researchers wrote.
“This evidence supports that W20-SPIONs were a successful oligomer-targeted MRI probe for early diagnostics of Parkinson’s and Huntington’s disease. Identification of reliable biomarkers of disease progression will play a key role in the diagnosis of neurodegenerative diseases, and also be important for the development and assessment of disease-modifying treatments,” they added.
Future studies will be required to show the safety and effectiveness of W20-SPIONs in the early-stage diagnosis of Parkinson’s disease and other neurodegenerative diseases in human patients.