Using a Nanochip to Deliver Alzheimer’s Therapy to the Brain

 

There are many challenges to tackling neurological diseases like Alzheimer’s, but one is the difficulty in developing drugs that can cross the blood-brain barrier. Researchers at the Technion-Israel Institute of Technology and Bar-Ilan University may have found a way around that problem. They utilized a nanochip that can be inserted just outside the brain beneath the skull that delivers a therapeutic. In their specific case, they used it to deliver a neural growth factor to treat Alzheimer’s disease. The research was published in the journal Small.

Previous research had shown that administering the protein neural growth factor inhibited damage to cholinergic mechanisms, the neurons in the brain typically damaged by another protein, beta-amyloid, in Alzheimer’s disease.

“In people with neurodegenerative diseases, the expression of the neural growth factor protein is reduced,” Ester Segal, from Technion, who led the research, told The Times of Israel.

Segal conducted the research with PhD student Michael Rosenberg from the Technion Faculty of Biotechnology and Food Engineering and Orit Shefi and PhD student Neta Zilony-Hanin from the Bar-Ilan University Faculty of Engineering.

The neural growth factor in other research has been shown to have restorative qualities, but it is difficult in getting it past the blood-brain barrier. There are ongoing clinical trials where the neural growth factor is injected directly into the brain by way of a catheter, but that is complicated, invasive and very risky, Segal said.

The nanochips were developed in Segal’s laboratory. They are made of a nanoscale porous structure that can be loaded with the protein. Segal and her team created a silicone structure that held the protein in its active form than slowly released it over about a month. Once the drug is released, the chips safely degrade and dissolve.

Segal indicates there are two possible ways to insert the chips directly into the brain. The first is via implant. The skull needs to be drilled into and, obviously, this is also an invasive approach. It’s less invasive than using a catheter, because the chip isn’t inserted directly into the brain, but is placed on the outer layer called the dura mater.

The second method is to use a “gene gun,” a device that was originally designed to insert DNA into plant cells. Shefi re-engineered the device, turning it into something similar to a nose spray. This injects the silicon chip loaded with the protein particles into the brain by way of the nose, bypassing the blood-brain barrier.

Segal told The Times of Israel that the nose has direct pathways to the brain. “Not for nothing drug addicts sniff cocaine via their noses.”

In research with mice models, the chips had the desired result. It has also been evaluated on a cellular model of Alzheimer’s disease, with the protein releasing and rescuing nerve cells. The group is currently running pre-clinical tests on animals and if the results are positive, move on to human clinical trials.

The authors note that the implanted mice were observed for eight weeks and no inflammation or adverse effects were observed. The researchers also believe they can engineer the chips for a longer release.