Parkinson's UK funded research suggests it may be possible to prevent the formation of protein clumps that cause problems in Parkinson’s by using microscopic "tweezers" that pull apart the proteins. This could pave the way for a therapy that could slow or stop the progression of the condition.
New research findings, published in the journal of Nature Communications, have shown potential for a type of drug molecule that can act as tiny molecular "tweezers". While still in the early stages of research, this class of drug holds promise as a future treatment for everyone with Parkinson's, because protein clumps are present in every individual with the condition.
The potential for this approach has also been seen in other neurodegenerative conditions like Alzheimer's.
One important new insight from this work was that these drugs might be more effective if they are given in the earliest stages of the condition. As Parkinson's can start many months or even years before the symptoms become apparent, detecting Parkinson's in its earliest stages is still a challenge research must overcome.
Toxic proteins and molecular tweezers
Precious dopamine producing brain cells are lost in Parkinson's, and researchers believe that toxic forms of a protein called alpha-synuclein are partly to blame for the death of these cells and also responsible for the spread of the condition.
An ongoing area of Parkinson's research is focusing on ways to clear toxic proteins and prevent the formation of clumps that clog up cells. In order to do this researchers around the world are looking at new drug molecules as well as immune therapies that may possess these abilities.
In this study, the team at the world-class Oxford Parkinson’s Disease Centre were investigating a new class of drug-like molecules that act like molecular "tweezers". They are described like this due to their shape, where the open space between the two "tweezers" is able to bind and trap proteins. In this case, the molecular tweezer CLR01 was shown to attach to alpha-synuclein, preventing the Parkinson's protein from sticking together and forming toxic clumps.
In mouse models of Parkinson's, CLR01 treatment reduced the levels of toxic protein clumps in the brain and reduced the appearance of movement problems. The research also showed that CLR01 was more effective when given to mice before they developed symptoms rather than to mice in the more advanced stages of the condition.
Dr Beckie Port, Research Manager at Parkinson’s UK, said:
"We desperately need treatments that protect brain cells in Parkinson's. These findings show that this innovative 'molecular tweezer' approach has exciting potential in the lab. We now need to take this therapy forward to test in clinical trials. Only then will we know whether it can do the same in people with Parkinson's."
Lead Researcher Dr Nora Bengoa-Vergniory said:
"Future investment to determine the appropriate therapeutic window for these kinds of therapeutic agents is crucial for the success of these and other therapeutic strategies."
Head of the Oxford Parkinson’s Disease Centre and senior author on the study Professor Richard Wade-Martins said:
"This is a very exciting piece of work showing that drug treatments can be developed to unpick toxic protein clusters to save neurons in models of Parkinson’s. Our work is focused on developing new approaches to saving neurons when they start to lose function early on, but before they die later on in the condition. This work should give encouragement to those ultimately hoping for protective therapies."
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