Nanobodies that target LRRK2 could have potential for Parkinson's

Treatments targeting a protein called LRRK2 are currently being tested in clinical trials for Parkinson's. Researchers hope they may have the ability to slow the progression of the condition which is something no current treatment can do.

There are multiple late stage clinical trials of LRRK2 inhibitors in progress. These existing studies are all based on chemical molecules that have been designed to reach the brain and interact with the LRRK2 protein. 
 
Now researchers in Belgium have discovered a new way to target the LRRK2 protein using nanobodies and published their findings in the scientific journal PNAS

What is LRRK2?

Researchers funded by Parkinson's UK, along with researchers in the US, first uncovered the link between LRRK2 and increased risk of Parkinson's in 2004. Since that time, it has been discovered that changes in the LRRK2 gene are the most common genetic cause of Parkinson’s. 
 
While genetic forms of the condition are rare, and for most people the causes of Parkinson's are unknown, the LRRK2 protein also seems to be involved where there is no known cause. This means targeting the LRRK2 may be beneficial for people with both sporadic Parkinson's and those carrying a LRRK2 mutation.

Treatments that target LRRK2

The LRRK2 protein is involved in many processes in the cell, and mutations in the gene make it overactive which contributes to the loss of brain cells and the development of Parkinson's. 
 
This has led to an interest in developing treatments that target LRRK2 with inhibitors that reduce the activity of the protein. However, long‐term inhibition of LRRK2 with these therapies may cause side effects. And so a pioneering team in Brussels went in search of other ways to target the LRRK2 protein that might cause less toxicity.

What are nanobodies?

Nanobodies are a type of antibody, a protein created by your immune system that helps you fight off infections. Nanobodies are 10 times smaller than a typical human antibody. They are found in camels and sharks and were first discovered around 25 years ago. 
 
Clinical trials of nanobody based therapies have already begun for the treatment of other conditions, including cancer and arthritis. Researchers are looking at the potential of nanobodies in Parkinson's, including ones that can interact with the alpha-synuclein protein.

What the team did

The researchers used lab based tests and cell models to identify LRRK2 inhibiting nanobodies. 
 
They found a series of nanobodies that interact with LRRK2 in different ways, including ones that may have fewer of the potential long term toxic effects that may impact LRRK2 inhibitors currently in clinical trials.
 
Dr Beckie Port, Head of Research Communications and Engagement at Parkinson’s UK, comments:

''With more than 40 symptoms, Parkinson’s can have a significant impact on daily life, and those living with the condition need better treatments urgently. 

''This is an encouraging study which provides a solid starting point for the development of the most promising nanobodies targeting LRRK2. However, further research is needed to better understand how these nanobodies work and if they have the potential to slow the progression of Parkinson's.''
 

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