Bioengineers have created a non-invasive method that uses ultrasound to assess gene expression and gene therapy delivery in specific areas of the brain.
Bioengineers have created a non-invasive method that uses ultrasound to assess gene expression and gene therapy delivery in specific areas of the brain.
The possibility of modifying or preventing the action of malfunctioning genes in the brain could serve as a significant treatment for neurodegenerative diseases. However, understanding the molecular dynamics within the living brain remains a challenge, hindering advancements in such promising treatments.
The current techniques for investigating the brain are limited. Biopsy, which involves taking tissue samples, remains the most reliable method to obtain molecular data from various genes; however, it is invasive and carries risks.
A recent study published in Science Advances unveils innovative technology by Jerzy Szablowski’s team at Rice University that may revolutionize gene therapy targeting the brain. The method, known as “Recovery of Markers through InSonation” or REMIS, allows for the measurement of gene therapy expression or natural genes in distinct brain regions without invasive procedures.
“Our limited capacity to assess gene expression poses significant challenges for the advancement of gene therapy,” Szablowski stated. “Typically, it is challenging to noninvasively verify whether gene therapy has successfully accessed the brain, the duration of its presence, and which regions are impacted. Our research demonstrates that we can measure gene expression and gene therapy delivery in specific brain areas using a relatively straightforward ultrasound method.”
REMIS builds upon previous work by Szablowski and his team that concentrated on engineered molecules called released markers of activity (RMAs). Through the RMA platform, the researchers were able to introduce a synthetic gene expression reporter into the brain, allowing for the production of a protein that could migrate from the brain into the bloodstream. This protein could be retrieved and measured with exceptional sensitivity; RMA expression could be detected in blood samples containing as few as 12 neurons.
However, the limitation of this initial technology was that the markers crossed the blood-brain barrier indiscriminately, making it impossible to trace them to specific areas of the brain. REMIS resolved this issue by leveraging ultrasound to transport engineered protein markers from targeted regions in the brain into the bloodstream.
“We have designed markers that remain inside blood vessels until ultrasound stimulation occurs,” Szablowski explained.
Furthermore, REMIS can also evaluate the natural expression of genes. An example is c-Fos, a gene recognized as a marker for neuronal activity. This suggests that REMIS holds promise not just for gene therapy but also as a valuable research and diagnostic tool.
“We are particularly thrilled about this technology, especially as our research has already paved the way for a funded clinical trial with our partners at Baylor College of Medicine and MD Anderson Cancer Center,” Szablowski noted.
The upcoming trial will employ focused ultrasound to release proteins found in the brains of Parkinson’s disease patients into the bloodstream, potentially offering new insights into the molecular aspects of the disease. However, Szablowski pointed out that a more immediate use for REMIS would be in tracking the effectiveness of gene delivery within the brain.
“Gene therapy represents an exhilarating frontier in medicine, but we need appropriate tools to verify whether the gene therapy reaches its intended location in the brain and operates as planned,” Szablowski expressed. “REMIS offers a non-surgical solution, potentially using the gene therapeutic itself as a marker, which is a significant advantage compared to methods like PET scans that require the development of new probes for each new therapeutic.”
