Medical researchers have long sought an answer to bypassing the blood-brain barrier, a layer of tightly packed cells that surrounds each of the blood vessels of the brain.
While this barrier helps protect the vessels from toxins and infections, it also prevents doctors from effectively treating brain diseases and tumors in patients.
A team of scientists at the Sunnybrook Health Sciences Center in Canada, however, have developed a non-invasive way to circumvent the blood-brain barrier in order to deliver much-needed drugs into the brain that could better treat diseases such as Parkinson’s and Alzheimer’s.
The breakthrough procedure makes use of focused ultrasound and microbubbles to bypass the protective layer around the brain’s blood vessels, and according to the researchers, it has already produced positive results in their clinical trials on animals.
The Sunnybrook scientists are now conducting tests in applying the new method on human patients.
The blood-brain barrier has been non-invasively opened in a patient
for the first time. A team at Sunnybrook Health Sciences Centre in
Toronto used focused ultrasound to enable temporary and targeted opening
of the blood-brain barrier (BBB), allowing the more effective delivery
of chemotherapy into a patient’s malignant brain tumor.
led by neurosurgeon Todd Mainprize, MD, and physicist Kullervo Hynynen,
PhD, infused the chemotherapy agent doxorubicin, along with tiny
gas-filled bubbles, into the bloodstream of a patient with a brain
tumor. They then applied focused ultrasound to areas in the tumor and
surrounding brain, causing the bubbles to vibrate, loosening the tight
junctions of the cells comprising the blood-brain barrier and allowing
high concentrations of the chemotherapy to enter targeted tissues.
blood-brain barrier has been a persistent impediment to delivering
valuable therapies to treat tumors,” said Dr. Mainprize. “We are
encouraged that we were able to open this barrier to deliver
chemotherapy directly into the brain, and we look forward to more
opportunities to apply this revolutionary approach.”
This patient treatment is part of a pilot study
of up to 10 patients to establish the feasibility, safety and
preliminary efficacy of focused ultrasound to temporarily open the
blood-brain barrier to deliver chemotherapy to brain tumors. The Focused Ultrasound Foundation is currently funding this trial through their Cornelia Flagg Keller Memorial Fund for Brain Research.
this barrier opens up a new frontier in treating brain disorders,” said
Neal Kassell, MD, Chairman of the Focused Ultrasound Foundation. “We
are encouraged by the momentum building for the use of focused
ultrasound to non-invasively deliver therapies for a number of brain
Opening the blood-brain barrier in a localized
region to deliver chemotherapy to a tumor is a predicate for utilizing
focused ultrasound for the delivery of other drugs, DNA-loaded
nanoparticles, viral vectors, and antibodies to the brain to treat a
range of neurological conditions, including various types of brain
tumors, Parkinson’s, Alzheimer’s and some psychiatric diseases.
procedure was conducted using Insightec’s ExAblate Neuro system. “This
first patient treatment is a technological breakthrough that may lead to
many clinical applications,” said Eyal Zadicario, Vice President for
R&D and Director of Neuro Programs, Insightec.
current trial is a first-in-human achievement, Dr. Kullervo Hynynen,
senior scientist at the Sunnybrook Research Institute, has been
performing similar pre-clinical studies for about a decade. His research
has shown that the combination of focused ultrasound and microbubbles
may not only enable drug delivery, but might also stimulate the brain’s
natural responses to fight disease. For example, the temporary opening
of the blood-brain barrier appears to facilitate the brain’s clearance
of a key pathologic protein related to Alzheimer’s and improves
A recent study
by Gerhard Leinenga and Jürgen Götz from the Queensland Brain Institute
in Australia further corroborated Hynynen’s research, demonstrating
opening the blood-brain barrier with focused ultrasound reduced brain
plaques and improved memory in a mouse model of Alzheimer’s disease.
on these two pre-clinical studies, a pilot clinical trial using focused
ultrasound to treat Alzheimer’s is being organized.
Anthony is an over thinker, and a person that worries too much. Anthony was that kid that always had questions that no one could answer such as: What would we do if the world ended today? How can we survive a zombie apocalypse if we had no weapons? Anthony worried about anything, and everything whether it was big or small this effected how he lived his life on a daily bases. He is very edgy, and easily startled. Like everyone else Anthony hates to be lied to, but the only difference is that he will stop at nothing until he has satisfaction of getting back in the worse way possible. This can go from burning your things to using your illness or fear against you.
Secret: "I’ve already killed about 5 people.“
Why you’re here: "I’m just worried about what will happen to me if i don’t get help.”
Drive-by shooting robbed baby of more than just its mother
The person who fatally shot a pregnant Toronto woman on the weekend robbed her prematurely delivered baby of more than just a mother — also gone are the child’s best chances for a healthy life.
Candice Rochelle Bobb, 35, was killed Sunday in a drive-by shooting while riding in the back seat of a car. Her baby boy was delivered by emergency caesarian section, then transported to the trauma centre at Sunnybrook Hospital, where he remained in stable condition Tuesday.
Doctors have the immediate challenge of keeping the baby alive.
The infant’s exact gestation period was unconfirmed but estimated at five months. Babies born between 22 and 26 weeks are classified as “extremely pre-term” or micro-preemie. Babies born at under 22 weeks are the most fragile of all, and have an extremely low rate of survival, according to the Canadian Neonatal Network.
If they do survive, micro-preemies face a much higher risk of chronic lung disease, intracranial (inside the skull) bleeding and an eye condition called retinopathy of prematurity, which can cause blindness, says Dr. Michael Narvey, section head of neonatology at the Children’s Hospital Research Institute of Manitoba.
The infant will usually spend the first five or six months of its life in hospital, likely needing help to breathe and eat.
In any event, it takes more than just feeding tubes and ventilation machines to sustain a baby’s development: what micro-preemies need most is a parent, according to experts.
They need contact, and especially skin-to-skin contact with their mother — so-called kangaroo care (KC), which has been shown to improve the baby’s breathing and sleep, helps stabilize the baby’s heart rate and seems to reduce pain. The Canadian Paediatric Society strongly encourages such skin-to-skin care.
“The effects of KC are dramatic and effective,” Narvey says on his blog, All Things Neonatal.
It “improves infant growth, breastfeeding and mother-and-infant attachment, which won’t happen here,” Narvey says.
It’s unclear whether the father of Bobb’s baby, or another family member, is available to step in.
But nothing can replace all the benefits — like increased immunity and resistance to infection — that come from a mother’s own milk, something that’s even more crucial for babies born prematurely than those born full-term.
Higher risk, but also hope
Down the road, extreme pre-term babies are at higher risk of cognitive, behavioural or physical impairment. One study published earlier this year in the journal Pediatrics found that more than half of infants born at under 28 weeks gestation went on to have “moderate or severe” cognitive deficits.
However, research conducted at Ottawa Hospital and the Children’s Hospital of Eastern Ontario suggests Bobb’s baby could still have a good outcome.
Of babies born at under 26 weeks gestation, the majority survive “free of disabilities or with what we would view as minor disabilities,” says Dr. Brigitte Lemyre, a neonatal ICU doctor at both hospitals who was involved in the study.
“Contrary to popular view, it’s not the majority of children born extremely premature that are severely disabled; it’s the minority,” she told CBC News. “The majority actually do well and thrive and have a very good quality of life, according to their parents and themselves when they grow up.”
It’s impossible to predict the long-term outcome of such an inauspicious birth.
“There are examples of babies who have done phenomenally well, who have no problem whatsoever, who were born at the extremes of gestation,” Narvey says.
Officials at Sunnybrook Hospital declined on Tuesday to provide any updates on Bobb’s baby.
As people grow older, they often have difficulty falling asleep and staying asleep, and tend to awaken too early in the morning. In individuals with Alzheimer’s disease, this common and troubling symptom of aging tends to be especially pronounced, often leading to nighttime confusion and wandering.
Now, a study led by researchers at Beth Israel Deaconess Medical Center (BIDMC) and the University of Toronto/Sunnybrook Health Sciences Center helps explain why sleep becomes more fragmented with age. Reported online today in the journal Brain, the new findings demonstrate for the first time that a group of inhibitory neurons, whose loss leads to sleep disruption in experimental animals, are substantially diminished among the elderly and individuals with Alzheimer’s disease, and that this, in turn, is accompanied by sleep disruption.
“On average, a person in his 70s has about one hour less sleep per night than a person in his 20s,” explains senior author Clifford B. Saper, MD, PhD, Chairman of Neurology at BIDMC and James Jackson Putnam Professor of Neurology at Harvard Medical School. “Sleep loss and sleep fragmentation is associated with a number of health issues, including cognitive dysfunction, increased blood pressure and vascular disease, and a tendency to develop type 2 diabetes. It now appears that loss of these neurons may be contributing to these various disorders as people age.”
In 1996, the Saper lab first discovered that the ventrolateral preoptic nucleus, a key cell group of inhibitory neurons, was functioning as a “sleep switch” in rats, turning off the brain’s arousal systems to enable animals to fall asleep. “Our experiments in animals showed that loss of these neurons produced profound insomnia, with animals sleeping only about 50 percent as much as normal and their remaining sleep being fragmented and disrupted,” he explains.
A group of cells in the human brain, the intermediate nucleus, is located in a similar location and has the same inhibitory neurotransmitter, galanin, as the vetrolateral preoptic nucleus in rats. The authors hypothesized that if the intermediate nucleus was important for human sleep and was homologous to the animal’s ventrolateral preoptic nucleus, then it may also similarly regulate humans’ sleep-wake cycles.
In order to test this hypothesis, the investigators analyzed data from the Rush Memory and Aging Project, a community-based study of aging and dementia which began in 1997 and has been following a group of almost 1,000 subjects who entered the study as healthy 65-year-olds and are followed until their deaths, at which point their brains are donated for research.
“Since 2005, most of the subjects in the Memory and Aging Project have been undergoing actigraphic recording every two years. This consists of their wearing a small wristwatch-type device on their non-dominant arm for seven to 10 days,” explains first author Andrew S. P. Lim, MD, of the University of Toronto and Sunnybrook Health Sciences Center and formerly a member of the Saper lab. The actigraphy device, which is waterproof, is worn 24 hours a day and thereby monitors all movements, large and small, divided into 15-second intervals. “Our previous work had determined that these actigraphic recordings are a good measure of the amount and quality of sleep,” adds Lim.
The authors examined the brains of 45 study subjects (median age at death, 89.2), identifying ventrolateral preoptic neurons by staining the brains for the neurotransmitter galanin. They then correlated the actigraphic rest-activity behavior of the 45 individuals in the year prior to their deaths with the number of remaining ventrolateral preoptic neurons at autopsy.
“We found that in the older patients who did not have Alzheimer’s disease, the number of ventrolateral preoptic neurons correlated inversely with the amount of sleep fragmentation,” says Saper. “The fewer the neurons, the more fragmented the sleep became.” The subjects with the largest amount of neurons (greater than 6,000) spent 50 percent or more of total rest time in the prolonged periods of non-movement most likely to represent sleep while subjects with the fewest ventrolateral preoptic neurons (less than 3,000) spent less than 40 percent of total rest time in extended periods of rest. The results further showed that among Alzheimer’s patients, most sleep impairment seemed to be related to the number of ventrolateral preoptic neurons that had been lost.
“These findings provide the first evidence that the ventrolateral preoptic nucleus in humans probably plays a key role in causing sleep, and functions in a similar way to other species that have been studied,” says Saper. “The loss of these neurons with aging and with Alzheimer’s disease may be an important reason why older individuals often face sleep disruptions. These results may, therefore, lead to new methods to diminish sleep problems in the elderly and prevent sleep-deprivation-related cognitive decline in people with dementia.”