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Ultrasound to boost Alzheimer’s treatment

An Australian research team funded by the AADRF, have recently discovered a feasible treatment for Alzheimer’s disease and frontotemporal dementia, as well as a way of enhancing the delivery of this treatment.

Lead author Dr Rebecca Nisbet, along with her research team from the Queensland Brain Institute, found that using non-invasive ultrasound scanning combined with a therapeutic molecule (RN2N) reduced Alzheimer's symptoms in mice.

The team believes that these findings will be translatable to humans in the future.

“One of the main causes of Alzheimer’s disease and frontotemporal dementia, two of the most common forms of dementia, is the aggregation of the protein tau within neurons. In our study we generated an antibody specific for tau (RN2N), and investigated its efficacy in clearing tau in a mouse model of frontotemporal dementia,” Dr Nisbet said.

“RN2N alone showed therapeutic efficacy and this was enhanced when delivery of RN2N was combined with scanning ultrasound.

“RN2N is an antibody we have generated which binds specifically to tau and prevents tau from being converted to a pathological form. As smaller molecules are taken up into the brain more readily than larger molecules, RN2N was engineered into a single-chain variable fragment (scFv) format, which is a sixth of the size of a full-length antibody, to facilitate its delivery into the brain.”

Significantly, the researchers found that using scanning ultrasound briefly opens up what is known as ‘the blood-brain barrier’ – a highly selective membrane that protects the brain by preventing anything potentially harmful from entering the central nervous system.

The barrier performs a very important role but it is also one of the biggest challenges for scientists attempting to treat neurodegenerative diseases such as Alzheimer’s disease.

 “Delivering drugs to the brain is inefficient due to the presence of the blood–brain barrier, which controls the passage of molecules from the blood into the brain. However, the ultrasound approach transiently opens the barrier, increasing the uptake of drug treatments such as RN2N and restoring memory functions,” she said.

Although it may be quite a few years before we see scanning ultrasounds used on humans, it is predicted that the combination of ultrasound and the delivery of a therapeutic molecule would significantly reduce the number of treatments a patient would require and therefore reduce the overall cost of treatment.

The discovery also means that this same ultrasound technique could be used to treat other neurodegenerative diseases such as Parkinson’s, MS and Motor Neuron disease more effectively.

“We are currently conducting safety trials of the scanning ultrasound in mice to ensure that repeatedly opening the blood-brain barrier is safe. Furthermore, we are constructing and optimising the machinery and treatment protocols for the use of scanning on larger mammals,” said Dr Nisbet.  

Dr Nisbet said that without funding from the AADRF she is not sure that this research project would have been completed.

“Funding for early career researchers is not only rare but also extremely competitive and because of this, many young researchers don’t get the opportunity to progress their academic career independently. Grants and fellowships provided by AADRF allow early career researchers to transition towards independent research and at the same time, make us competitive for future funding,” she said.

Sources: 

The study published in Brain was funded through lead author Dr Rebecca Nisbet who received an AADRF Postdoctoral Fellowship in 2013.

For more information on grants or to apply click here.

To support researchers such as Rebecca, please click here.

Pictured: Dr Rebecca Nisbet

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