New Non-Invasive Technique Controls the Size of Molecules Penetrating the Blood-Brain Barrier
A new technique developed by Elisa Konofagou, professor of biomedical engineering and radiology at Columbia Engineering, has demonstrated for the first time that the size of molecules penetrating the blood-brain barrier (BBB) can be controlled using acoustic pressure — the pressure of an ultrasound beam — to let specific molecules through. The study was published in the July issue of the Journal of Cerebral Blood Flow & Metabolism.
“This is an important breakthrough in getting drugs delivered to specific parts of the brain precisely, non-invasively, and safely, and may help in the treatment of central nervous system diseases like Parkinson’s and Alzheimer’s,” says Konofagou, whose National Institutes of Health Research Project Grant (R01) funding was just renewed for another four years for an additional $2.22 million. The award is for research to determine the role of the microbubble in controlling both the efficacy and safety of drug safety through the BBB with a specific application for treating Parkinson’s disease.
Most small — and all large — molecule drugs do not currently penetrate the BBB that sits between the vascular bed and the brain tissue. “As a result,” Konofagou explains, “all central nervous system diseases remain undertreated at best. For example, we know that Parkinson’s disease would benefit by delivery of therapeutic molecules to the neurons so as to impede their slow death. But because of the virtually impermeable barrier, these drugs can only reach the brain through direct injection and that requires anesthesia and drilling the skull while also increasing the risk of infection and limiting the number of sites of injection. And transcranial injections rarely work — only about one in ten is successful.”
Focused ultrasound in conjunction with microbubbles — gas-filled bubbles coated by protein or lipid shells — continues to be the only technique that can permeate the BBB safely and non-invasively. When microbubbles are hit by an ultrasound beam, they start oscillating and, depending on the magnitude of the pressure, continue oscillating or collapse. While researchers have found that focused ultrasound in combination with microbubble cavitation can be successfully used in the delivery of therapeutic drugs across the BBB, almost all earlier studies have been limited to one specific-sized agent that is commercially available and widely used clinically as ultrasound contrast agents. Konofagou and her team were convinced there was a way to induce a size-controllable BBB opening, enabling a more effective method to improve localised brain drug delivery.
Konofagou targeted the hippocampus, the memory center of the brain, and administered different-sized sugar molecules (Dextran). She found that higher acoustic pressures led to larger molecules accumulating into the hippocampus as confirmed by fluorescence imaging. This demonstrated that the pressure of the ultrasound beam can be adjusted depending on the size of the drug that needs to be delivered to the brain: all molecules of variant sizes were able to penetrate the opened barrier but at distinct pressures; that is, small molecules at lower pressures and larger molecules at higher pressures.
“Through this study, we’ve been able to show, for the first time, that we can control the BBB opening size through the use of acoustic pressure,” says Konofagou. “We’ve also learned much more about the physical mechanisms associated with the trans-BBB delivery of different-sized agents, and understanding the BBB mechanisms will help us to develop agent size-specific focused ultrasound treatment protocols.”
Konofagou and her Ultrasound Elasticity Imaging Laboratory team plan to continue to work on the treatment of Alzheimer’s and Parkinson’s in a range of models, and hope to test their technique in clinical trials within the next 5 years.
“It is frightening to think that in the 21st century we still have no idea how to treat most brain diseases,” Konofagou adds. “But we’re really excited because we now have a tool that could potentially change the current dire predictions that come with a neurological disorder diagnosis.”
Related News
-
News CPHI Frankfurt 2022: Innovator Interview – DSM Biomedical
At CPHI Frankfurt we spoke to Anne-Cecile Bayne, Global Science & Innovation Lead Pharma and Medical Nutrition, and Marc Hendriks, Vice President Strategy & Business Development, on their expertise in nitrosamines and business strategy at DSM Biomedica... -
News New WHO health emergency guidelines expect full transparency from Big Pharma
The WHO are proposing a new set of pandemic guidelines to set out how future global health crises should be handled. -
News Magic mushrooms could be used to treat mental health conditions
A compound found in magic mushrooms, psilocybin, could be used to treat mental health conditions and help patients suffering with severe depression, as shown by the results of the largest study of its kind to date. -
News UK-based partnership to launch DETERMINE study into rare cancer research
UK-based CRO Quanticate is set to partner with Cancer Research UK for the launch of the DETERMINE study focused on testing a range of existing and approved drugs and therapies on rare cancers. -
News FDA approves Thermo Fisher blood tests for wheat and sesame allergies
Both tests have been approved by the US regulator for in vitro diagnostic use -
News QIAGEN launches world’s first syndromic test for monkeypox
The test can distinguish between monkeypox and other diseases that cause similar symptoms. -
News Monkeypox Update: Vaccine shortage, sewage surveillance and global testing
As concern over the monkeypox outbreak continues to rise, we take a look at major developments from the first week of August. -
News CPHI Podcast Series: The importance of novel excipients for innovative drug development
The latest episode in the CPHI Podcast Series dives into the world of novel excipients and explores their importance for innovative drug development.
Position your company at the heart of the global Pharma industry with a CPHI Online membership
-
Your products and solutions visible to thousands of visitors within the largest Pharma marketplace
-
Generate high-quality, engaged leads for your business, all year round
-
Promote your business as the industry’s thought-leader by hosting your reports, brochures and videos within your profile
-
Your company’s profile boosted at all participating CPHI events
-
An easy-to-use platform with a detailed dashboard showing your leads and performance