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NF2 Gene Therapy Demonstrates Proof-of-Concept

By November 4, 2020December 18th, 2023NF Summit, NF2-SWN, Science & Research

Encouraging results from NF2 gene therapy studies in animals show that the approach of introducing a “healthy” copy of the NF2 gene to animal models of the disorder has value. This exciting news was shared with the community in a virtual Family Forum presented by the Children’s Tumor Foundation “The Past, Present, and Future of NF2 Research.”

With funding provided by the Children’s Tumor Foundation, Dr. Long-Sheng Chang of Nationwide Children’s Hospital / The Ohio State University showed how inborn changes in the human NF2 gene interfere with its ability to tell the body to make a key protein called merlin. Merlin’s role is to suppress tumor formation, so a lack of merlin allows the growth of tumors such as the vestibular schwannomas (acoustic neuromas), characteristic of this disorder.

The goal of NF2 gene therapy is to introduce a normal, working version of the NF2 gene to the tissues where it is needed. There it should  increase levels of merlin in the target tissue. In theory, normalization of merlin levels should shrink or slow the growth of tumors. Along the way to achieving successful gene therapy are multiple hurdles such as the possibility of toxicity, the challenges delivering the gene to the target area and of showing that it works to “rescue” the situation by cause tumors to grow more slowly or to shrink.

Major progress toward this goal is happening now in both mouse and monkey models of NF2.

In animal models of NF2, new strains are bioengineered to lack a working copy of the NF2 gene. Dr. Marco Giovannini of the University of California, Los Angeles, discussed his lab’s results in an NF2 mouse model. So far, they have successfully introduced a normal NF2 gene and showed that it reached the target tissue (tumor). The next milestone – discovering whether or not NF2 tumors in these mice respond to gene therapy by showing shrinkage or slowed growth —  is anticipated in 2021.

A crucial step on the path to making NF2 gene therapy a reality is proving this concept works in a monkey model. Michael Wootton, CEO of NF2 Therapeutics, announced that the first phase of testing in a monkey model of NF2 found no evidence of toxicity. This is very encouraging news, but the crucial next step is to find out whether the replacement NF2 gene finds its target and is able to function normally to enhance merlin levels in the tumor.

This next milestone – defining location and expression of the new gene — is expected by the end of 2020.  Based on this, Dr. Wootton responded to an audience question by saying that first human clinical trials could begin in late 2022 or early 2023.

View the NF2 Forum below or click here to view on YouTube: