Facilitating Drug Delivery by Unlocking the Blood-Nerve Barrier

A research team led by UCL has opened and closed the blood-nerve barrier for the first time and used it to deliver drugs to target tissues.

Research published in developmental cellIt has the ability to deliver tumor-killing drugs to the nervous system, as well as prevent side effects of chemotherapy that result from damage to the peripheral nervous system.

The blood-nervous barrier is less well understood than the associated blood-brain barrier, which prevents substances in the blood from reaching the sensitive environments of the brain and peripheral nerves. They also act as a barrier to drugs, so the latest study sought to identify new ways to deliver drugs into the nervous system, without causing harm.

Lead author Professor Alison Lloyd, Director of UCL’s Laboratory of Molecular Cell Biology, explained, “We have identified the structure and control of the blood and nerve barrier – the types of cells involved, how they interact, how they might be regulated and why this is a barrier. It took more than 10 years of development, but we have Now a powerful model enables us to control and understand the opening and closing of the barrier.”

“Our discovery that the barrier can be opened in a reversible way is important in the pursuit of drug delivery into the nervous system, as permanently breaking these barriers would be toxic. We have shown you that it can help drugs cross the barrier for a limited time, reducing the potential for side effects. “.

For the study, Prof. Lloyd and her colleagues determined the structure and function of the blood-nerve barrier, finding that it is ‘more leaky’ than the blood-brain barrier, but is reinforced by macrophages (a type of white blood cell) that specifically engulf leaky material.

Using these insights, the researchers devised a way to trigger a signal to open the septum in a mouse model long enough to deliver drugs called anti-allergy oligonucleotides into the peripheral nervous system.

Although the researchers say their early-stage paper is important to neuroscience because bypassing the blood-nerve barrier may facilitate treatment for a variety of conditions. For example, chemotherapy for cancer can have an unpleasant side effect called peripheral neuropathy, in which people feel burning, tingling, or numbness in their hands and feet due to peripheral nerve damage. This research may contribute to the development of drugs that can be added to chemotherapy to reduce these side effects.

This research also has a much broader application beyond cancer. Diabetes can also cause peripheral neuropathy, so the knowledge from this research could make managing diabetes much easier in the future. The drugs used in this study, antisense oligonucleotides, are currently undergoing trials for diseases such as Huntington’s and Duchenne muscular dystrophies, so there is potential for better care of many difficult-to-treat diseases.