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Advancing Brain Health with Tech

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Elisa Konofagou, the Robert and Margaret Hariri Professor of Biomedical Engineering is dedicated to pioneer innovative ultrasound-based techniques with applications in both imaging and therapeutic fields. Her research group has developed algorithms to identify even the most subtle tissue deformations caused by physiological processes, such as those occurring in the heart and blood vessels. They have also devised methods to detect displacements induced by ultrasound waves, especially relevant in tumours and nerves.

Furthermore, the team leverages focused ultrasound technology to facilitate drug delivery to the brain without invasive procedures by opening the blood-brain barrier (BBB).

The BBB is a natural protective barrier within the brain that typically hinders the penetration of systemic medications, posing a significant challenge for treating various brain disorders. They also utilise focused ultrasound to modulate neural activity within the central and peripheral nervous systems.

To ensure the practical application of these ground-breaking technologies, the research team collaborates closely with medical professionals at the Columbia University Irving Medical Centre. Their collaborative efforts aim to bridge the gap between laboratory innovation and clinical practice, ultimately bringing these transformative technologies to needy patients.

For many years, researchers have pursued the ambitious goal of utilising gene therapy to treat numerous neurological conditions, including Alzheimer’s and Parkinson’s diseases. However, they have encountered a significant hurdle in the form of the blood-brain barrier, which has proven to be exceptionally challenging to breach.

Over the last four years, Konofagou has collaborated with Kam Leong. Together, they have been working on a novel approach to deliver gene-editing vectors, carriers that are genetically engineered to transport genetic material, to the brain. They achieve this by employing focused ultrasound and microbubbles to open the formidable blood-brain barrier.

Konofagou’s research group has extended the application of this technology to address Alzheimer’s disease specifically. Alzheimer’s is the predominant neurodegenerative disorder, and it is anticipated to witness a significant increase in its incidence over the next decade due to advances in early detection and the overall ageing of the population.

The research team has recently released two papers showcasing substantial technological progress. The first paper highlighted that using focused ultrasound in combination with microbubbles administered systemically facilitates genome editing and amplifies gene copies by a factor of 20.

This groundbreaking technology permits the delivery of gene-editing vectors capable of modifying the genetic makeup of neuronal cells. It holds the potential to rectify genes associated with brain disorders like Alzheimer’s, including genes such as ApoE4 and ApoE2, as well as address other rare, monogenic brain pathologies.

The second paper illustrated that opening mice’s blood-brain barrier (BBB) activates the brain’s immune system. This activation subsequently reduces the levels of beta-amyloid and tau, which are the two defining proteins associated with Alzheimer’s disease.

Moreover, this process enhanced working memory in the mice. When the researchers applied the focused ultrasound technique to clinical trials involving Alzheimer’s patients, they observed a modest reduction in beta-amyloid levels within the region where the BBB was opened compared to the untreated contralateral brain region.

Collectively, these two papers provided compelling evidence that focused ultrasound has the potential to advance Alzheimer’s disease treatment through two distinct approaches: enhancing the delivery and expression of gene-editing tools and utilising focused ultrasound for immunomodulation. Importantly, this innovative technique can simultaneously activate gene editing and immunomodulation methods.

Konofagou emphasised that the combined impact of these approaches could be a game-changer in the treatment of Alzheimer’s, particularly during its early stages. She expresses significant enthusiasm about the possibilities this presents.

The Konofagou research group is presently conducting clinical trials to assess the efficacy of their focused ultrasound technique in Alzheimer’s patients. Their goals include reducing the levels of both tau and beta-amyloid proteins and improving memory deficits. Additionally, they are collaborating with the Leong research group to facilitate the translation of their gene-editing technique into clinical applications.


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