Κυριακή, 22 Νοεμβρίου 2015

BBB PENETRATED SAFELY

Doctors at Sunnybrook Health Sciences Centre in Toronto, Ontario, Canada, have noninvasively penetrated the blood-brain barrier to deliver a chemotherapeutic agent directly into a patient’s malignant brain tumor.
This is the first time that the blood-brain barrier has been safely breached in a human, the researchers say.
The blood-brain barrier has long thwarted the delivery of chemotherapeutic and other agents into the brain.
But the Toronto doctors hope that the technique they used, focused ultrasound, will continue to be successful in safely penetrating what has been a persistent obstacle to treating not only brain tumors but also other diseases, such as Alzheimer's disease and Parkinson's disease
"I want to stress that this has only been done in one patient, a 56-year-old woman with glioblastoma, and the result, as exciting as it is, is as preliminary as it gets," neurosurgeon Todd Mainprize, MD, from the University of Toronto, told Medscape Medical News.
"This is a proof-of-concept phase 1 clinical study to make sure that when we open up the blood-brain barrier we don't cause any hemorrhages or infection, and that we can safely and effectively deliver a drug where in the brain we want to," Dr Mainprize said.
Dr Mainprize confessed he was a bit surprised by the intense media interest that this case generated.
"I can't stress enough that this is a phase 1 trial. We do not have a published paper, we have only done this in one patient so far. That being said, we think this is a very exciting treatment and has a lot of potential applications in the future. But it is essentially a drug delivery method," he said.
The Sunnybrook team planned to test focused ultrasound in 10 patients as part of their phase 1 trial. However, because the first case went so well, they will probably only do 4 before they go into a phase 2 trial, Dr Mainprize said.
"We will see, this is only the first patient, but the results have been so conclusive, it appears to be quite safe. We'll see how the others go and we may just stop before 10 patients," he said.
The researchers infused the chemotherapy agent doxorubicin, along with tiny gas-filled bubbles, into the bloodstream of the patient. They then applied focused ultrasound to areas in the tumor and surrounding brain, causing the bubbles to oscillate and bypass the tight junctions of the cells of the blood-brain barrier.
"We think that the oscillation in size where the cells swell and shrink pokes holes in the blood-brain barrier and allows the various drugs or whatever to cross the blood-brain barrier into the substance of the brain," Dr Mainprize explained.
"In our first patient we could clearly see enhancement in the area that we opened. We could see that the gadolinium was crossing the blood-brain barrier into the brain, making that area turn white where we opened it, as shown on the MRI sequences we obtained. It clearly worked in this patient, there is no doubt that we were able to open the blood-brain barrier safely, without any problems, based on the gadolinium uptake," he said.
"We’re very excited about it and we think there are many potential [uses] for this drug delivery system, but I have to stress that this is very early and there will not be widespread applications for a while," Dr Mainprize said.
Focused Ultrasound for Alzheimer's and Parkinson's
Elisa Konofagou, PhD, professor in the Department of Biomedical Engineering at Columbia University, New York, New York, and her group are also studying focused ultrasound for the opening of the blood-brain barrier for drug delivery in both Alzheimer's disease and Parkinson's disease.
"We have done some work in mice and monkeys and we have shown both neuroprotection and neurorestoration in mouse models of Parkinson's disease by opening the blood-brain barrier and delivering a neurotrophic factor. We have also shown that drug delivery through the ultrasound-induced blood-brain barrier also works in nonhuman primates," Dr Konofagou told Medscape Medical News.
he added that her group has secured funding by the National Institutes of Health to begin clinical trials on using focused ultrasound for blood-brain barrier opening in patients with Alzheimer's, after having shown preliminary results on feasibility in mouse models.
The work was supported by the Focused Ultrasound Foundation, the Canada Foundation for Innovation and Ontario Ministry of Research and Innovation, the Bombardier Foundation, the Canadian Institutes of Health Research, and the National Institutes of Health.

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