Two new studies have found that using focused ultrasound to open up the blood-brain barrier generated a positive immune response in the brain and allowed for the admission of gene-editing technology. The technique could be a non-invasive way of treating neurodegenerative diseases such as Alzheimer’s and Parkinson's.
The blood-brain barrier (BBB) is a nifty, natural protective membrane that prevents dangerous pathogens and toxins in the blood from entering the brain. But, from a medical perspective, the BBB can be a drawback because it impedes the entry of drugs and biopharmaceuticals used to treat brain diseases.
However, researchers from Columbia University have found a way of opening up the BBB to allow the delivery of important drugs and gene therapy right to where they’re needed most. They recently published two papers, both highlighting the effectiveness of using non-invasive focused ultrasound (FUS) to provide access to the BBB.
The first study, published in the journal PNAS, demonstrated the use of focused ultrasound and systematically administered microbubbles to open the BBB and enable the admission of CRISPR gene editing technology. Combining FUS with CRISPR-encoded viral vectors, the researchers achieved more than 25% editing efficiency in mouse neurons.
They say their findings suggest that by using FUS, it’s possible to edit the genome of neuronal cells and potentially correct genes that code for brain diseases such as Alzheimer’s disease, such as ApoE4 and ApoE2. Previous studies have found that the ApoE4 gene is an important risk factor for Alzheimer’s, whereas ApoE2 is protective.
In the second study, published in the journal Theranostics, the researchers showed that using FUS alone triggered an immune response in the brains of mice that lowered beta-amyloid and tau loads, the two proteins known to accumulate in Alzheimer’s disease, and improved working memory.
When they applied the FUS technique to Alzheimer’s patients, they found a modest reduction in beta-amyloid in the area of the BBB that was treated compared to the untreated area.
Taken together, the researchers say the results of these studies show that FUS could be used to treat Alzheimer’s disease by triggering an immune response or allowing the delivery of gene-editing technology. It’s also possible that the novel technique could induce both gene editing and immunomodulation at the same time..
“The resulting synergistic effect could prove pivotal in the treatment of Alzheimer’s, especially at its early stages,” said Elisa Konofagou, a corresponding author in both studies. “We’re very excited about this.”
The studies were published in the journals PNAS and Theranostics.
Source: Columbia Engineering, Columbia University