Partners team up for long-awaited trial of CMT4J gene therapy
CureCMT4J, CMT Research Foundation share costs to fund manufacturing
Patient advocacy organizations CureCMT4J and the CMT Research Foundation (CMTRF) are teaming up with Elpida Therapeutics for a clinical trial of ELP-02, an experimental gene therapy for CMT4J, an ultra-rare form of Charcot-Marie-Tooth disease (CMT).
“Our collaboration with Elpida Therapeutics and CMTRF enables us to move forward, inching closer to a clinical trial and finally having the opportunity to show that our gene therapy works for CMT4J,” Jocelyn Duff, executive director and co-founder of CureCMT4J, said in a written interview with Charcot-Marie-Tooth News.
The announcement comes after years of delay in the gene therapy’s development. Preclinical studies have shown promise, and regulators have given the OK to start clinical testing in people. But manufacturing gene therapy product for a clinical trial is expensive, and there simply hasn’t been enough funding to run the trial.
The two advocacy organizations are collectively chipping in $1.5 million — $700,000 from CureCMT4J and $800,000 from CMTRF — to help cover costs associated with manufacturing clinical-grade gene therapy doses for the trial. If all goes well, the trial will start dosing patients in early to mid-2026, according to a CMTRF press release.
“By funding the manufacturing of clinical-grade doses for phase I/II trials, CMTRF and its partners are enabling rapid movement from lab to patient, with the trial expected to begin treating individuals in [the second quarter of] 2026,” Laura M. MacNeill, CEO of CMTRF, told Charcot-Marie-Tooth News.
Gene therapy could be ‘lifesaving treatment’
CMT4J is a subtype of CMT that’s caused by mutations in the FIG4 gene. The disease is marked by muscle weakness in the arms and legs, with CMT symptoms starting in early childhood to adulthood. Motor function impairment and sensory loss are also associated with the disorder.
ELP-02 is designed to deliver a healthy version of the FIG4 gene to the body’s cells, addressing the underlying cause of CMT4J. The therapy is administered by injection into the spinal canal (intrathecal injection), and it delivers its genetic payload using a modified version of a virus called adeno-associated virus (AAV). Vectors based on AAV are commonly used in gene therapies, because the virus is relatively easy to work with in a lab and doesn’t typically cause illness in people.
ELP-02 treatment rescued nerve function, improved motor strength, and extended survival in a mouse model of CMT4J.
CureCMT4J, an all-volunteer research organization, has been spearheading the therapy’s preclinical development.
“This could be a lifesaving treatment for some CMT4J patients,” Duff said. “Some of our patients are still walking and hope that a gene therapy might keep them out of a wheelchair. Others hope to keep breathing on their own or to maintain the current function of their hand and arm strength. We all want to maintain or improve quality of life.”
For Duff, bringing the therapy into clinical development is a deeply personal matter. There are fewer than 100 known cases of CMT4J in the world, and one of them is Duff’s daughter, Talia.
“As the parent of Talia, who has CMT4J, I live day-to-day with the devastation of this disease and the desperation and urgency necessary to try to stop it,” Duff said.
Duff and other advocates have been pushing to bring ELP-02 into clinical trials for years, but the journey has been difficult. Developing a new therapy for any disease is never easy — the vast majority of experimental therapies fail in preclinical or clinical testing. But developing treatments for ultra-rare disorders like CMT4J poses additional unique challenges.
“For ultra-rare diseases, just reaching that human clinical trial stage with a gene therapy is an enormous challenge, with a lack of funding being the biggest obstacle,” Duff said. Preclinical studies and other early steps in drug development can cost millions, Duff noted — and companies are often wary of investing in therapies for rare diseases, since by definition there aren’t many patients who will buy an approved treatment. As a result, Duff said, “it is often a Rare Parent or patient who sparks, funds and coordinates all of the necessary steps to approach drug development.”
”At the heart of it, all we want is to give our children a better life.”
Terry Pirovolakis, CEO of Elpida, is intimately familiar with the challenges of developing rare disease gene therapies. Like Duff, Pirovolakis is the parent of a child with a rare disease: His son Michael was diagnosed with a rare genetic disorder called SPG50 in 2019.
“Terry is a self-taught drug developer who has made endless contacts throughout the world since his son’s diagnosis. He understands the nuances of manufacturing and regulatory challenges,” Duff said. “Most of all, Terry and his small team at Elpida understand the urgency required to try to develop treatments to save and transform the lives of patients currently living with these rare diseases.”
Pirovolakis has spent years as a rare disease advocate, ultimately leading to the creation of Elpida, which was launched as a nonprofit-styled company focused on developing gene therapies for rare diseases that affect kids.
“Our goal was to support programs stuck in academia, but it has evolved into rescuing and advancing life-saving therapies,” Pirovolakis told Charcot-Marie-Tooth News. “At the heart of it, all we want is to give our children a better life.”
Despite the hurdles, there was reason for hope: Preclinical research on ELP-02 had been promising, and the gene therapy was slated to enter clinical testing in 2020. But then plans were scuttled by the COVID-19 pandemic.
“Nearly all non-Covid research came to a screeching halt and the biotech investor economy collapsed, causing the shelving of many gene therapy programs, including ours,” Duff said. In the five years since, Duff said, she has been “trying to pick up the pieces to move it forward again.”
Preclinical data point to treatment’s potential
“We have the science and technology in place,” said Duff. “We only need the funding to get it off the shelf and into the patients who have been waiting for far too long.”
After years of scrambling for funding, the CMTRF stepped in to provide the final infusion of cash needed to launch clinical testing.
“The collective power of the expertise of our three nonprofits is powerful and could serve as a model for other ultra-rare collaborations,” Duff said. “We are so grateful and absolutely thrilled to have CMTRF on our team!”
MacNeil said the CMTRF was motivated to invest in the therapy in part because the preclinical data “demonstrated great potential—showing that ELP-02 restores nerve function in disease models, with promising data on efficacy and safety.” This comes as the U.S. Food and Drug Administration announced a new process to streamline rare disease drug approvals, mostly supported by data from a well-designed study.
The CMTRF hopes that results from the trial will not only benefit people with CMT4J, but lay the groundwork to develop treatment for other types of CMT.
“This trial is among some of the most promising CMT research with the greatest likelihood of leading to clinical trials or approved therapies in the near term,” MacNeill said. “What we learn from this gene therapy approach for the CMT4J Elpida project will contribute to our larger understanding of how to cure other CMT subtypes and a range of devastating neurological conditions.”
Among them could be amyotrophic lateral sclerosis (ALS) and Parkinson’s disease, according to MacNeill. “Patient groups and stakeholders are excited by the potential to accelerate progress using technologies proven to be safe and effective in rare conditions,” MacNeill said.
The design for the upcoming trial is being finalized. Pirovolakis said the study will likely look at the therapy’s effect on markers of muscle degeneration and nerve damage, with the aim of supporting an application seeking accelerated approval —a type of conditional approval where a therapy is allowed to be marketed in the U.S. based on early data it’s likely effective, while requiring additional testing to confirm efficacy.
“This is a ‘hope and a prayer’ approach necessitated by the urgency of rare diseases’ devastating consequences and unmet needs,” Pirovolakis said. “I want to express our deepest gratitude to CMTRF and CureCMT4J for entrusting us and believing in Elpida through this significant grant. Together, we will bring hope and work toward giving these patients a better life.”
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