Parkinson’s research: Experimental nanobody targets toxic proteins

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Parkinson’s disease (PD) affects at least 8.5 millionTrusted Source people worldwide, most of them aged over 60. 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 may indicate other disorders, so these numbers are almost certainly an underestimate.

Common symptoms include tremors, muscle rigidity, and slowness of movement. Some people also experience pain, anxiety, and depression.
Currently, there is no cure for PD, although existing treatments can help manage the symptoms and improve quality of life.

A number of factors are responsible for the symptoms, such as low dopamine levelsTrusted Source, low norepinephrine levelsTrusted Source, and clumps of a protein called alpha-synucleinTrusted Source in the brain.

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

Now, scientists from Johns Hopkins University have genetically engineered a nanobodyTrusted Source to target alpha-synuclein clumps in the brain and destabilize them. The research could lead to new treatments for Parkinson’s disease.

Why nanobodies
Nanobodies, or single-domain antibodies, are the smallest fragment of an antibody with binding ability. They are highly stable and can penetrate into tissues.

Dr. Melita Petrossian, neurologist, 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 — inside the brain cells — so nanobodies would be expected to be more effective against PD than traditional antibodies.”
In this study, researchers genetically modified a nanobody that could get through the tough exterior of brain cells. By removing disulfide bonds in the nanobody, they ensured that it remained stable once inside the brain cells, allowing it to bind with alpha-synuclein clumps.
The advantage of this nanobody, named PFFNB2, is that it binds only to the alpha-synuclein clumps that cause the symptoms of Parkinson’s disease.

It does not bind to single molecules of alpha-synuclein that researchers believe to be important in the transmissionTrusted Source of nerve impulses.