Non-invasive Brain Stimulation Opens Blood-Brain Barrier

US scientists demonstrate how ultrasound can deliver drugs to the brain

Researchers at the WVU Rockefeller Neuroscience Institute (RNI) in West Virginia, USA, have once again demonstrated in a pilot study how non-invasive brain stimulation (NIBS) can increase the benefit of drug therapies. The work was published in the New England Journal of Medicine in the first week of January 2024. The shock waves of transcranial pulse stimulation (TPS) also achieve this effect.

Blood-brain barrier cannot be penetrated by many drugs

The blood-brain barrier (BBB) is an important protective barrier in the human brain that prevents the penetration of harmful substances from the bloodstream into the brain tissue. One of the main reasons why many drugs are unable to cross the BBB is due to its chemical and physical nature. The BBB mainly allows small, lipophilic (fat-soluble) molecules to pass, while larger or hydrophilic (water-soluble) molecules are often excluded. Many drugs are either too large or not lipophilic enough to penetrate the BBB.

In addition, specific transport mechanisms play a role. Some substances are actively transported across the BBB by transport proteins, while others are actively filtered out by efflux pumps. These pumps, such as the P-glycoprotein pump, play an important role in protecting the brain, but can also impair the effectiveness of drugs by transporting them out of the brain tissue before they can take effect.

Brain stimulation can overcome the normally impermeable barrier

Recent studies have shown that ultrasound waves, for example, can safely and reversibly open this barrier under certain conditions. This technique offers the potential to improve the effectiveness of drugs for the treatment of neurological diseases by allowing the drugs to cross the normally impermeable barrier and enter the brain tissue directly. This approach could play a significant role in the treatment of diseases such as Alzheimer’s, Parkinson’s or brain tumors by enabling more targeted and effective drug delivery.

Reduction of beta-amyloid concentration in brain regions irradiated with ultrasound

In their pilot study, US scientists from the RNI led by neuroscientist Ali Rezai investigated the use of ultrasound in the treatment of dementia patients. They used aducanumab, the first beta-amyloid drug to be approved in the USA, although it has not been approved by the European Medicines Agency (EMA) for the treatment of Alzheimer’s dementia. This monoclonal antibody aims to reduce the beta-amyloid deposits in the brain that are characteristic of Alzheimer’s and are thought to play a key role in the development of the disease. The challenge, however, is that the biotech substance needs to reach the brain effectively in order to be effective.

The research team carried out a treatment in three patients aged 77, 59 and 64 who were diagnosed with Alzheimer’s disease during 2023. These patients received monthly infusions of the drug aducanumab. In addition, ultrasound therapy was applied to one side of the brain at the same time. The opening of the blood-brain barrier was detected by complex imaging procedures for a period of 24 to 48 hours. In the course of the treatment, the beta-amyloid deposits in the brain were measured and compared with the deposits in the half of the brain that was not treated with ultrasound.

Study leader Ali Rezai from the RNI is confident about the results of the study. He sees this progress as a new hope for the treatment of the 6.7 million Americans affected by Alzheimer’s and sees it as an important step towards addressing this urgent medical need, says the neuroscientist.

Shockwave therapy Transcranial Pulse Stimulation (TPS) also opens the blood-brain barrier

These effects can also be seen with the lowertic shock waves of transcranial pulse stimulation (TPS), as TPS researcher Prof. Dr. med. Dr. rer. nat. Ulrich Sprick, Heinrich Heine University Düsseldorf (HHU) from the Alexius/Josef Hospital in Neuss reports: “The blood-brain barrier is opened or even completely removed for a certain period of time by TPS. This has been scientifically proven. And during this period of opening or complete removal of this barrier, active pharmaceutical ingredients can in turn enter the brain and have an optimal effect in the right places. Until now, the problem has always been that active pharmaceutical ingredients could not really get to where they were needed. With TPS, we have finally found a door opener.” (see also: