Powerful chemotherapy drug reaches brain tumors using novel ultrasound technology
Treating brain cancer, specifically glioblastoma, has long been a challenge for medical professionals due to the blood-brain barrier, which prevents potent chemotherapy from reaching the aggressive brain tumor. However, Northwestern Medicine scientists have introduced a new skull-implantable ultrasound device that can perforate the blood-brain barrier and deliver substantial amounts of chemotherapy intravenously.
The results of the first-in-human clinical trial indicate that the treatment is safe and well-tolerated. This opens a new path for glioblastoma patients who previously did not have effective treatment options.
Increasing drug concentration in the brain
Ultrasound-based blood-brain barrier opening allowed for an approximately four- to six-fold increase in drug concentrations in the human brain. Dr. Adam Sonabend, the lead investigator and associate professor of neurological surgery at Northwestern University Feinberg School of Medicine, explained that, in the past, direct paclitaxel injection into the brain showed promising signs of efficacy, but it was associated with toxicity, such as brain irritation and meningitis.
The current chemotherapy drug for glioblastoma, temozolomide, does cross the blood-brain barrier, but it is a weak drug. Effective repurposing of drugs to treat brain pathology and cancer require their delivery to the brain, which the ultrasound technology facilitates, as it opens a window of about one hour, during which the drug can penetrate the brain.
Improving the sequence of drug delivery
The Northwestern researchers discovered how quickly the blood-brain barrier closes after sonication and observed that the blood-brain barrier is fully restored 24 hours after brain sonication. Based on some animal studies, it was assumed that the blood-brain barrier is open for about six hours. The study shows that this time window might be shorter.
The scientists used a grid of nine ultrasound emitters designed by French biotech company Carthera, which opens the blood-brain barrier in a volume of brain nine times larger than that of the initial single-ultrasound emitter implant. Most encouragingly, the results are the basis for the ongoing clinical trial, in which patients with recurrent glioblastoma receive a combination of paclitaxel and carboplatin delivered to their brain with the ultrasound technique.
– The blood-brain barrier is a microscopic structure that shields the brain from the vast majority of circulating drugs, so patients with brain cancer cannot be treated with most drugs that are otherwise effective for cancer elsewhere in the body.
– Patients undergo surgery for resection of their tumors and implantation of the ultrasound device.
– The treatment prolongs the survival of patients with recurrent glioblastoma.
The blood-brain barrier has long been a barrier to effective brain cancer treatment. But Northwestern Medicine scientists have developed a new ultrasound technology that perforates this structure, allowing for chemotherapy to penetrate the brain four to six times more effectively. Spreading the technique over a large region of the brain allows for glioblastoma treatment without the toxic side effects that come with injecting chemotherapy directly into the brain.
The success of the first-in-human clinical trial is a great stride forward in the treatment of brain cancer, particularly glioblastoma, which is rapidly fatal without treatment. The skull-implantable ultrasound device used in the trial was safe and well-tolerated, and patients could receive up to six cycles of treatment. The tremendous increase in drug concentrations in the human brain is a breakthrough in drug delivery, and the ongoing phase two clinical trial will shed even more light on the treatment’s efficacy in prolonging the survival of patients with recurrent glioblastoma.