Nanocapsules show multiple benefits in Parkinson’s mouse model
Therapy boosts dopamine, reduces neuroinflammation
Therapeutic nanocapsules designed to simultaneously increase dopamine levels and decrease neuroinflammation were able to improve motor and cognitive function in a mouse model of Parkinson’s disease, a study found.
The scientists who developed the nanodrug, which was also engineered to have enhanced brain delivery, said they believe that simultaneously targeting two important disease-related processes will enable better disease control than existing therapeutic strategies.
“Our findings provide a new strategic avenue for advancing the treatment of PD [Parkinson’s disease] and pave the way for future research and clinical applications of targeted, synergistic nanotherapeutics in the field of neurodegenerative diseases,” the researchers wrote.
The study, “Parkinson Disease -Targeted Nanocapsules for Synergistic Treatment: Combining Dopamine Replacement and Neuroinflammation Mitigation,” was published in Advanced Science.
A significant challenge in treating neurological diseases like Parkinson’s is designing therapies able to cross over the selective blood-brain barrier (BBB) and reach the brain. The BBB is a tight-knit layer of cells that protects the brain by preventing substances circulating in the bloodstream from passing through. The vast majority of small molecules — about 98% of them — can’t cross it.
Breaching the BBB
Tiny molecules called nanoparticles that are engineered to be able to breach the BBB may be promising for treating Parkinson’s. They can be used as carrier molecules for therapeutics, but can also be engineered so that the nanoparticles themselves have therapeutic properties.
In the study, the researchers engineered a Parkinson’s nanodrug that would have dual therapeutic effects: increasing levels of dopamine, the brain signaling chemical that’s deficient in Parkinson’s, while reducing neuroinflammation, which is implicated in Parkinson’s neurodegeneration.
To achieve this, the nanocapsules were partly made of dopamine. They were also loaded with catalase, an enzyme that can modulate neuroinflammation signaling pathways.
Modifications were made for enhanced brain delivery and BBB passage. First, the catalase was linked to a peptide called cRGD that recognizes and binds to a protein known to be elevated in the BBB of people with Parkinson’s disease. The outsides of the nanocapsules were also coated with a protein called angiopep-2, which has a high affinity for another BBB component.
In a cell culture model designed to mimic the brain environment seen in Parkinson’s patients, the therapy was able to be taken by the cells, appeared very stable under neural conditions, and exerted therapeutic effects.
The nanocapsules reduced signs of oxidative stress, a type of cell death implicated in Parkinson’s, and improved the function of mitochondria, the energy-producing compartments of cells that are known to be dysfunctional in the neurodegenerative disease. They also showed the potential to restore more normal dopamine signaling.
In Parkinson’s mice, the nanocapsules could cross the BBB and reach the brain. This was associated with improvements in motor and cognitive function in the mice.
On a cellular level, the treatment was found to restore more normal dopamine signaling, including increases in dopamine levels and higher activity of dopamine signaling-related proteins. It also reduced neuroinflammation, as intended.
Treatment did not appear to have any negative effects on other organs, including the liver, kidney, heart, spleen, or lungs.
“Collectively, these findings underscore the favorable … biocompatibility of the [nanocapsules], highlighting their potential as therapeutic agents,” the scientists wrote.
By targeting both dopamine loss and neuroinflammation simultaneously, the therapeutic approach will be able to both ease disease symptoms as well as slow disease progression in the long term, “offering a synergistic approach to PD therapy,” that’s lacking with current treatment approaches, the researchers wrote.
“This study demonstrates the potential of biocompatible, multi-target nanoformulations in overcoming the limitations of current PD treatments,” they concluded.
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