An Interview with RareCast’s Danny Levine

Part of our mission at CMT Research Foundation is to raise awareness about the progress we are making in finding a cure for CMT in the medical, scientific, pharma and patient communities. So, I was pleased to be interviewed on a podcast hosted by Global Genes a non-profit corporation advocating for rare disease globally.  You can listen to the entire 24-minute podcast  or read some highlights from our conversation below.  Many thanks to Daniel Levine at RareCast!

Global Gene’s Daniel Levine: We think of the complexity of developing therapies for single gene disorders. How complicated is it to get a diagnosis or develop a therapy for a condition where so many different genes might be implicated?

Susan Ruediger: The good news is that there are four genes that are implicated for four of the most common types of CMT. Four genes are responsible for 90 percent of the people who have CMT, and one gene is responsible for over 50 percent. The good news about CMT is they’re all monogenic diseases, meaning that only one gene defect is causing the disease…So, applying gene therapy to one of those four types, is underway right now.

Daniel Levine: This is a condition that was first medically recognized in 1886, a hundred thirty-five years ago. Yet, there’s no approved therapies to treat the condition, even though it is among the most prevalent rare diseases. Why is that?

Susan Ruediger: … the first gene was identified 31 years ago for the most common type, CMT 1A, the type that I happen to have. So, why 31 years and we don’t have treatments yet? I think there are a number of reasons for that. One is there are some real key barriers pharmaceutically to treating a disease like CMT. For example, how do you reach the peripheral nervous system, how do you deliver a drug to every teeny, tiny peripheral nerve, how do you measure efficacy in a slowly progressive disease, and is it possible to regenerate nerves that have already died? These are questions that we’re working on answering scientifically…I think the other piece that can be very frustrating from the patient community is the lack of awareness about CMT and its severity within the medical and pharmaceutical communities.

Then I think the pharmaceutical industry has looked at CMT historically and says, you know, it’s not killing people, it’s mild, and they’re diseases that are far more severe that will require our attention earlier. I think really that nobody’s strongly shinned a light on the importance of CMT. This is one of the reasons why Pat (Livney) and I started the research foundation because we know that there’s this lack of awareness and this lack of interest and we are here to change that.

Daniel Levine: When you started the foundation, what was the intent?

Susan Ruediger: To deliver treatments and cures for CMT. We have one single focus at the research foundation and everyone who works with us—our board, our scientific advisory board, our staff, and our volunteers—we’re all focused on one thing and that’s funding research that’s going to lead to treatments and cures for CMT. That was our original intent and it remains our single focus. It’s the only reason why we exist.

Daniel Levine: Walk me through those. What are the biggest barriers you face?

Susan Ruediger: The first one, we already talked about, is how to deliver drugs to the peripheral nervous system. If we’re talking about a gene therapy, what we’re seeing in other diseases, like spinal muscular atrophy, is that the gene therapy is being injected into the spine and it’s transducing throughout the entire spine, which is terrific and becoming curative for those kids. How do we get a therapy into every tiny peripheral nerve in your fingers, toes, legs, arms, et cetera. That has been a key barrier that we’ve identified. The way that we’ve attacked it is by finding partners who focus on delivering gene therapies and saying, can you apply that focus to CMT? Let me give you a couple examples for that. I went to a meeting with Chris Austin, who was then the director of NCATS over at the National Institutes of Health, and I said to him, “it’s a big problem overcoming the delivery of a therapy to the peripheral nervous system.” Dr. Austin told me to go to James Dahlman at Georgia Tech, he is one of the very best in delivering gene therapies to different systems in the body, and talk to him about how to deliver to the peripheral nervous system. We talked with him and our scientific advisory board met with him. We designed a project, we provided funding, and we started that with Dr. Dahlman. So, it’s knowing exactly what our barrier is and finding all of the people who can work on that.

Another is the problem of addressing a hundred different genes known right now, and then hundreds of mutations in some of those genes that cause CMT. Are we going to have to deliver a genetic therapy for each individual mutation? That could be hundreds, maybe even thousands of different precision individualized medicines. Instead, are there learnings we can take from other genetic diseases that we can apply to CMT that have broader relatability to either one whole gene and all the mutations in that, or even multiple genes. Are there ways that we can knock out and replace genes with the right thing, one therapy that can address those types. Instead of showing a pharmaceutical company hundreds, or maybe thousands, of different approaches, showing them a handful and showing how that could have broad appeal to larger groups.

Daniel Levine: How is your organization funded and what do you do to get the biggest bang for your buck?

Susan Ruediger: Our organization right now is solely funded by the donor community. What we’re finding the donor community to be is mostly the patient community, patients, families, people who have this very close connection to CMT, and people who understand the burden of living with CMT and want to end the legacy that they may have given to their children or to their grandchildren.

Daniel Levine: Yeah. How do you maximize the return on what, I imagine, is a limited pool of investment you’re working with?

Susan Ruediger: One of the things that we’ve been able to do is provide seed funding to key partners and then have them raise more money for CMT. Let me give an example to you to put that in real world [terms]. Back to the delivery issue, we identified a company, DTX Pharma. We found them at BIO, an international conference of pharmaceutical companies. DTX focuses on delivering gene therapy to different systems. We pursued them, had a meeting and said, does your technology apply to CMT? They met with our scientific advisory board and said yes, it does. We gave DTX Pharma, $125,000 in January of 2019. Eight months later, DTX Pharma received a grant from the NIH to continue the same CMT project for $350,000. Then six months later it closed a series B round of financing for $100 million with CMT being one of two lead indications. They would never have started a CMT program if we hadn’t introduced them to the disease and given them the seed funding. Because of that seed funding, their data was so good because their technology was so well suited for CMT, that they were able to raise a hundred million plus. Now their commitment is to take their drug all the way through to clinical trials. That’s what we do, we’re catalytic funding. That was $125,000 of donor money that is now preparing for clinical trials.