Scientists are making nanobodies that could treat Parkinson’s disease

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Could an experimental nanobody change the future of Parkinson’s therapy? Credit: Andriy Onufriyenko/Getty Images,
  • Parkinson’s disease is a progressive, neurodegenerative disease that is increasing in prevalence worldwide.
  • There is currently no cure for the condition, which causes tremors, muscle weakness and mood swings.
  • Now scientists have developed a nanobody that can unravel the malformed proteins in the brain that lead to many of the symptoms of Parkinson’s disease.
  • This finding could hold the key to researching the disease and developing new treatments.

Parkinson’s disease (PD) affects at least 8.5 million People worldwide, most of them over 60 years old. According to the World Health Organization (WHO), the number has more than doubled in the past 25 years.

Diagnosis is difficult in the early stages as many of the symptoms can be indicative of other conditions, so these numbers are almost certainly underestimated.

Common symptoms include tremors, muscle stiffness and slowness of movement. Some people also experience pain, anxiety, and depression.

There is currently no cure for PD, although existing treatments can help manage symptoms and improve quality of life.

A number of factors are responsible for the symptoms, such as: low dopamine levels, low norepinephrine levelsand clumps of a protein called alpha synuclein in the brain.

These clumps form the structural core of Lewy bodies, which cause loss of nerve cells, leading to changes in movement, thinking, behavior, and mood, which are the main symptoms of PD.

Now scientists at Johns Hopkins University have genetically modified nanobodies to target and destabilize clumps of alpha-synuclein in the brain. The research could lead to new treatments for Parkinson’s disease.

They report on their findings nature communication.

Nanobodies or single domain antibodies are the smallest fragments of an antibody with binding ability. They are very stable and can penetrate tissue.

dr Melita Petrossian, neurologist and director of the Center for Movement Disorders at Providence Saint John Health Center in Santa Monica, California, said Medical news today:

“Compared to a conventional antibody, a nanobody is about 90% smaller and can therefore penetrate a cell better. This is important because much of the alpha-synuclein pathology is found intracellularly – inside the brain cells – so nanobodies are expected to be more effective against Parkinson’s than traditional antibodies.”

In this study, the researchers genetically modified a nanobody that could penetrate through the hard exterior of brain cells. By removing disulfide bonds in the nanobody, they ensured that it remained stable in brain cells and could bind to clumps of alpha-synuclein.

The benefit of this nanobody, called PFFNB2, is that it only binds to clumps of alpha-synuclein that cause the symptoms of Parkinson’s disease.

It doesn’t bind to individual molecules of alpha-synuclein, which researchers believe they are important in the transfer of nerve impulses.

First, the researchers tested the nanobody in vitro on mouse brain tissue. They found that PFFNB2 could bind to aggregates of alpha-synuclein but could not prevent clump formation.

Further experiments showed that the nanobody could bind and break up already formed fibrils of alpha-synuclein, thereby 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 declared for MNT the “[t]The results showed that they were able to target the preformed fibrils of alpha-synuclein in cell and mouse models, were able to reduce clumping (aggregation) of alpha-synuclein in cell models, and were able to reduce alpha-synuclein. Synuclein Pathology in Mouse Models.”

dr Xiaobo Mao, lead investigator on the study and associate professor of neurology at Johns Hopkins University, states the following about the clinical potential of this discovery:

“The success of PFFNB2 in binding clumps of harmful alpha-synuclein in increasingly complex environments suggests that the nanobody could hold the key to helping scientists study these diseases and eventually develop new treatments.”

According to the authors, these findings could represent a major step forward in the search for effective treatments for Parkinson’s and related disorders. “We anticipate these PFFNB-related agents as a potential therapeutic strategy against [alpha-synuclein]-associated 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]alongside lifestyle choices like exercise and healthy eating,” she told us.

“I’m confident that researchers can organize a human clinical trial soon, but we need to see safety, tolerability and efficacy in humans before nanobodies can reach the general population,” she added.

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