[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.