[Congressional Record Volume 170, Number 104 (Thursday, June 20, 2024)]
[Senate]
[Pages S4163-S4164]
From the Congressional Record Online through the Government Publishing Office [www.gpo.gov]
Glioblastoma
Mr. DURBIN. Madam President, I ask unanimous consent to have printed
in the Record an article that appeared in the Chicago Tribune a year
ago on May 3, 2023, be printed in the Record.
There being no objection, the material was ordered to be printed in
the Record, as follows:
Powerful Chemotherapy Drug Reaches Brain Tumors Using Novel Ultrasound
Technology
A major impediment to treating the deadly brain cancer
glioblastoma has been that the most potent chemotherapy can't
permeate the blood-brain barrier to reach the aggressive
brain tumor.
But now Northwestern Medicine scientists report results of
the first in-human clinical trial in which they used a novel,
skull-implantable ultrasound device to open the blood-brain
barrier and repeatedly permeate large, critical regions of
the human brain to deliver chemotherapy that was injected
intravenously.
The four-minute procedure to open the blood-brain barrier
is performed with the patient awake, and patients go home
after a few hours. The results show the treatment is safe and
well tolerated, with some patients getting up to six cycles
of treatment.
This is the first study to successfully quantify the effect
of ultrasound-based blood-brain barrier opening on the
concentrations of chemotherapy in the human brain. Opening
the blood-brain barrier led to an approximately four- to six-
fold increase in drug concentrations in the human brain, the
results showed.
Scientists observed this increase with two different
powerful chemotherapy drugs, paclitaxel and carboplatin. The
drugs are not used to treat these patients because they do
not cross blood-brain barrier in normal circumstances.
In addition, this is the first study to describe how
quickly the blood-brain barrier closes after sonication. Most
of the blood-brain barrier restoration happens in the first
30 to 60 minutes after sonication, the scientists discovered.
The findings will allow optimization of the sequence of drug
delivery and ultrasound activation to maximize the drug
penetration into the human brain, the authors said.
``This is potentially a huge advance for glioblastoma
patients,'' said lead investigator Dr. Adam Sonabend, an
associate professor of neurological surgery at Northwestern
University Feinberg School of Medicine and a Northwestern
Medicine neurosurgeon.
Temozolomide, the current chemotherapy used for
glioblastoma, does cross the blood-brain barrier, but is a
weak drug, Sonabend said.
The paper was published May 2 in The Lancet Oncology.
The blood-brain barrier is a microscopic structure that
shields the brain from the vast majority of circulating
drugs. As a result, the repertoire of drugs that can be used
to treat brain diseases is very limited. Patients with brain
cancer cannot be treated with most drugs that are otherwise
effective for cancer elsewhere in the body, as these do not
cross the blood-brain barrier. Effective repurposing of drugs
to treat brain pathology and cancer require their delivery to
the brain.
In the past, studies that injected paclitaxel directly into
the brain of patients with these tumors observed promising
signs of efficacy, but the direct injection was associated
with toxicity such as brain irritation and meningitis,
Sonabend said.
Blood-brain barrier recloses after an hour
The scientists discovered that the use of ultrasound and
microbubble-based opening of the blood-brain barrier is
transient, and most of the blood-brain barrier integrity is
restored within one hour after this procedure in humans.
``There is a critical time window after sonification when
the brain is permeable to drugs circulating in the
bloodstream,'' said Sonabend, also a member of the Robert H.
Lurie Comprehensive Cancer Center of Northwestern University.
Previous human studies showed that the blood-brain barrier
is completely restored 24 hours after brain sonication, and
based on some animal studies, the field assumed that the
blood-brain barrier is open for the first six hours or so.
The Northwestern study shows that this time window might be
shorter.
In another first, the study reports that using a novel
skullimplantable grid of nine ultrasound emitters designed by
French biotech company Carthera opens the blood-brain barrier
in a volume of brain that is nine times larger than the
initial device (a small single-ultrasound emitter implant).
This is important because to be effective, this approach
requires coverage of a large region of the brain adjacent to
the cavity that remains in the brain after removal of
glioblastoma tumors.
Clinical trial for patients with recurrent glioblastoma
The findings of the study are the basis for an ongoing
phase 2 clinical trial the scientists are conducting for
patients with recurrent glioblastoma. The objective of the
[[Page S4164]]
trial--in which participants receive a combination of
paclitaxel and carboplatin delivered to their brain with the
ultrasound technique--is to investigate whether this
treatment prolongs survival of these patients. A combination
of these two drugs is used in other cancers, which is the
basis for combining them in the phase 2 trial.
In the phase 1 clinical trial reported in this paper,
patients underwent surgery for resection of their tumors and
implantation of the ultrasound device. They started treatment
within a few weeks after the implantation.
Scientists escalated the dose of paclitaxel delivered every
three weeks with the accompanying ultrasound-based blood-
brain barrier opening. In subsets of patients, studies were
performed during surgery to investigate the effect of this
ultrasound device on drug concentrations. The blood-brain
barrier was visualized and mapped in the operating room using
a fluorescent dye called fluorescein and by MRI obtained
after ultrasound therapy.
``While we have focused on brain cancer (for which there
are approximately 30,000 gliomas in the U.S.), this opens the
door to investigate novel drug-based treatments for millions
of patients who suffer from various brain diseases,''
Sonabend said.
Other Northwestern authors include: A. Gould, C. Amidei, R.
Ward, K. A. Schmidt, D.Y. Zhang, C. Gomez, J.F. Bebawy, B.P.
Liu, I.B. Helenowski, R. V. Lukas, K. Dixit, P. Kumthekar, V.
A. Arrieta. Lesniak, H. Zhang and R. Stupp.
The work is funded by the National Cancer Institute of the
National Institutes of Health, the Lou and Jean Malnati Brain
Tumor Institute of the Lurie Cancer Center and SPORE support
from the Moceri Family Foundation and the Panattoni family.
Mr. DURBIN. Madam President, I am a liberal arts lawyer. I am not a
doctor, and I am not a researcher. So when I get into these fields, I
want to say the words I use very carefully, not to misstate what is
clearly the case.
But this was an amazing article, which is entitled ``Device uses
microbubbles to open blood-brain barrier to treat glioblastoma in
humans.''
It is the story of Northwestern Medicine scientist Adam Sonabend:
[R]eport results of the first in-human clinical trial using
a skull-implantable ultrasound device to open the blood-brain
barrier and repeatedly permeate large, critical regions of
the human brain.
To try to translate this into simple words, the blood-brain barrier
is something I don't understand. When we take two beers and drink them,
we can feel it, so the alcohol has permeated the blood-brain barrier.
But in the ordinary course of events, it is, in fact, a barrier for
chemicals to enter the brain.
Dr. Sonabend is finding a way to get beyond that barrier, and it is
for the treatment of what is known as glioblastoma, brain cancer. We
know that very well on a personal basis here in the U.S. Senate. We
have lost John McCain to glioblastoma; Ted Kennedy to glioblastoma; one
of our Democratic cloakroom staffers, Tim Mitchell, to glioblastoma;
and Hunter Biden's brother, Beau Biden, died from glioblastoma.
Why? I am going to try to say this in simple words, and I hope I
don't misstate it. Because when we discover the tumor, the first
reaction is surgery to remove the tumor. And so you will see, with each
of the people I have just mentioned, that experience take place. The
tumor is removed, but unfortunately the chemotherapy that is common to
stop cancerous tumors from emerging in the same area can't be used
because of the blood-brain barrier. This barrier stops the application
of the medicine. So the researchers are finding a way to get beyond
that barrier to bring chemotherapy to the brain of those suffering from
glioblastoma.
We lost the individuals that I mentioned earlier because the followup
was so difficult because of this barrier. Now, that is as far as I can
go in layman's terms explaining the situation, but the reason I raise
that issue is because it is timely.