- Parkinson’s disease is a progressive, neurodegenerative disorder that is becoming more common worldwide.
- There is currently no cure for the condition, which causes tremors, muscle weakness, and mood swings.
- Now scientists have designed a nanobody that can untangle the misshapen proteins in the brain that lead to many of Parkinson’s symptoms.
- This finding may be key to studying the disease and developing new treatments.
Parkinson’s disease (PD) affects at least
Diagnosis is difficult in the early stages because many of the symptoms can indicate other conditions, so these numbers are almost certainly an underestimate.
There is currently no cure for PD, although there is treatments can help manage symptoms and improve quality of life.
These clumps form the structural core of Lewy bodiesthat cause a loss of nerve cells, leading to changes in movement, thinking, behavior, and mood that are the main symptoms of PD.
Now scientists at Johns Hopkins University have genetically engineered it
They report their findings in
Nanobodies, or single-domain antibodies, are the smallest fragment of an antibody with binding capacity. They are very stable and can penetrate tissues.
dr. Melita Petrossianneurologist and director of the Movement Disorders Center at Providence Saint John’s Health Center in Santa Monica, CA, told Medical news today:
“Compared to a traditional antibody, a nanobody is about 90% smaller and therefore better able to enter a cell. This is important because much of the alpha-synuclein pathology is found intracellularly — in the brain cells — so nanobodies are expected to be more effective against PD than traditional antibodies.”
In this study, researchers genetically modified a nanobody that could penetrate the hard exterior of brain cells. By deleting Disulfide Compounds in the nanobody, they made sure that once inside the brain cells, it remained stable, allowing it to bind with alpha-synuclein clumps.
The advantage of this nanobody, called PFFNB2, is that it only binds to the alpha-synuclein clumps that cause the symptoms of Parkinson’s disease.
It doesn’t bind to some of the molecules of alpha-synuclein that researchers think is
Initially, the researchers tested the nanobody on mouse brain tissue in vitro. They found that PFFNB2 could bind to aggregates of alpha-synuclein, but failed to prevent the formation of clumps.
Further experiments showed that the nanobody could bind to and disrupt alpha-synuclein fibrils that had already formed, destabilizing the malformed proteins.
The researchers then tested this in live mice and found that the nanobody prevented alpha-synuclein from spreading to the cerebral cortex. The cortex is the largest part of the brain and is responsible for most of the higher brain functions.
dr. Petrossian explained for: MNT That “[t]The results showed that they were able to specifically target the preformed fibrils of alpha-synuclein in cell and mouse models, they were able to reduce the clumping (aggregation) of alpha-synuclein in cell models, and they were in able to reduce alpha-synuclein. synuclein pathology in mouse models.”
dr. Xiaobo MaoThe study’s lead researcher and associate professor of neurology at Johns Hopkins University notes the following about the clinical potential of this discovery:
“The success of PFFNB2 in binding harmful alpha-synuclein clumps in increasingly complex environments indicates that the nanobody could hold the key to help scientists study these diseases and ultimately develop new treatments.”
According to the authors, these findings could be a major step forward in the search for effective treatments for PD and related conditions. “We expect these PFFNB-related agents to show promise as a potential therapeutic strategy against [alpha-synuclein]-related pathogenesis,” they write.
dr. Petrossian agreed. “If these results are confirmed in human clinical trials, it is very likely that these nanobodies will be a very important part of the treatment of PD and DLB [dementia with Lewy bodies]in addition to lifestyle choices such as exercise and healthy diet,” she told us.
“I am hopeful that the researchers will soon be able to organize a clinical trial in humans, but we will need to see the safety, tolerability and efficacy in humans before nanobodies can reach the general population,” she added.