Gene Therapy Targets Chronic Pain

Scientists at New York University have developed a gene therapy for chronic pain. The technology works by targeting the NaV1.7 sodium ion channel present on neurons, which is an important component of the pain response. The researchers encoded a version of a peptide that allows a modulatory protein, called CRMP2, to bind to NaV1.7 sodium ion channels and modulate their activity. Treating neurons so that they now express this peptide interfered with the ability of CRMP2 to affect the sodium channel, reducing the transmission of pain. As chronic pain affects a large number of patients, new treatments such as this could be set to make a real difference in many lives.

Gene therapy has huge potential, but has progressed more slowly than was first anticipated when we first started exploring it. Part of the issue lies in developing safe ways to manipulate genes in the body without causing side-effects, and also identifying the most appropriate genetic targets that are implicated in disease. These NYU researchers have identified one such target in chronic pain, a condition which is estimated to affect one in three Americans.

The target is related to a sodium ion channel called NaV1.7 that is present in neurons. The importance of this channel in pain perception was discovered through the study of rare genetic disorders. In some such families, this channel is dysfunctional, allowing too much sodium to enter the neuron, resulting intense pain. However, in other families, the channel is blocked, leading to a complete absence of pain.

Researchers have tried to develop small molecule drugs to target NaV1.7, so far without much success. These researchers took a different approach, and have used gene therapy to target a protein called CRMP2 that modulates the activity of the NaV1.7 sodium ion channel. CRMP2 binds to the sodium channel, and it is this peptide binding site that is encoded by the new gene therapy.

The researchers used an adeno-associated virus to package and deliver the genetic material directly to neurons. When expressed by neurons, the peptide limits the ability of CRMP2 to modulate NaV1.7, reducing pain. So far, the approach has reduced pain in mice who experienced sensitivity to cold, heat and touch.  

“We found a way to take an engineered virus — containing a small piece of genetic material from a protein that all of us have — and infect neurons to effectively treat pain,” said Rajesh Khanna, a researcher involved in the study. “We are at the precipice of a major moment in gene therapy, and this new application in chronic pain is only the latest example.”    

Study in journal Proceedings of the National Academy of Sciences: Identification and targeting of a unique Na V 1.7 domain driving chronic pain

Via: New York University