Alzheimer’s is a progressive disease that leads to loss of memory and other important functions due to a build-up of plaque in the brain. This plaque is made up of a jumble of misfolded amyloid proteins and blocks communication between brain cells which creates many of the symptoms associated with Alzheimer’s. One drug that is known to reduce this plaque is called Aduhelm, which has antibodies that travel through the bloodstream and into the brain to target the amyloid proteins. An issue with this treatment is that it is very difficult for drugs to pass through the blood-brain barrier, so much of the drug goes to waste. This is one reason why the drug is so expensive. At $28,000 a year, it’s virtually impossible for the everyday person suffering from Alzheimer’s to use it for treatment. The blood-brain barrier is not a “shield” that covers the entirety of the skull. Instead, the barrier is at the end of major blood vessels in the brain. The job of the barrier is to prevent large molecules that may be harmful to the brain from getting in while allowing small molecules like glucose and oxygen to get in. So, Aduhelm alone reduces the amount of plaque in the brain, but only by a small amount because most of the antibodies do not get through to the brain. The only way for the antibodies to get in is if the blood-brain barrier is opened. How could this be done without damaging blood vessels and capillaries?
Dr. Ali Rezai, a neurosurgeon at the Rockefeller Neuroscience Institute of West Virginia University has come up with a way to solve this problem. He is leading a study that uses ultrasound to open up the blood-brain barrier to allow the passage of drugs. Funded by West Virginia University and the Harry T. Mangurian Jr. Foundation for Medical Research in cancer and brain diseases, this study is not testing the functionality of the treatment yet, it is testing the safety of the treatment. Three patients with mild Alzheimer’s have gone through the treatment and have described it as a painless procedure. The treatment begins with an injection of tiny microbubbles of perfluorocarbon gas that are commonly used for ultrasound imaging studies of the heart and liver and are proven to be safe to use as they are cleaned out of the body by the kidneys and liver after the procedures. Next, the patient lies on an MRI table and puts on a specialized helmet. Then, pulses of low-frequency ultrasound waves are focused in an area the size of a pencil. In this study, areas of the brain involved with memory and reasoning were treated first. The ultrasound creates a wave pattern in the fluid of the blood vessels which causes the microbubbles to expand and contract. This opens up the blood vessels and the blood-brain barrier and allows the drug to pass through to the brain. Although this treatment is a breakthrough in neuroscience, scientists will need a more efficient way to tackle the plaque caused by Alzheimer’s disease because the plaque is everywhere but the ultrasound can only target the tip of a pencil sized area.
Despite this trial only testing the safety of this method, the patients’ scans showed that the plaque in their brain had reduced by 32%. Since the ultrasound method was focused on one side of the brain, the scientists were able to compare the use of the ultrasound versus the drug alone and it showed that the ultrasound had reduced the plaque about 50% more than the drug alone. There have been no changes in the abilities of the patients but this treatment will hopefully slow down the progression of the disease. Also, Dr. Rezai has gained approval from the FDA to try using different frequencies and wavelengths of the ultrasound and different drugs to see if he can reverse the damage already done to some brain cells which would cure Alzheimer’s disease altogether.
Dr. Rezai is leading another study for helping drug addiction through an implant in the brain. This implant is commonly used to treat Parkinson’s disease by using deep brain stimulation to stop tremors. Dr. Rezai is using this same technology to place the implantation device on the part of the brain responsible for behavioral regulation, anxiety, and cravings which is also known as the reward center. The procedure entails cutting a nickel sized hole into the skull and placing a thin wire connected to four electrodes on the brain. Next, the wire is connected to a device placed below the collarbone that will send impulses to the electrodes. From this safety trial, one patient had a minor relapse, one patient dropped out of the trial, and the other two patients have been drug free since their operations. Dr. Rezai then combined this research with his Alzheimer’s research and thought that instead of highly invasive surgery, the patient could receive this deep brain stimulation from the ultrasound aimed at the reward center of the brain, the nucleus accumbens. Within this study, 10 out of the 15 patients have remained drug-free since their treatment. Although nothing can be concluded yet about the studies, the ultrasound technology seems to be useful in treating many diseases within the brain.
Since this technology has been so successful, many neuroscientists have been using it in their own studies to treat a variety of diseases affecting the brain. Dr. Nir Lipsman, a neurosurgeon at the Sunnybrook Research Institute of the University of Toronto has been leading a study that uses ultrasound technology to help treat breast cancer patients that have had the cancer spread to their brain. Dr. Lipsman uses the ultrasound to open up the blood-brain barrier to deliver a drug called trastuzumab that decreases the size of the tumors. From this research, they have reported that the amount of the drug that passed through the barrier increased four times the amount of not using the ultrasound. This technology is something to keep our eyes on as many success stories about treating brain diseases will be published soon thanks to the work of Dr. Ali Rezai and his team.
