What is GNE Myopathy?
GNE Myopathy (GNEM), also known as HIBM, is a rare genetic muscle disease that occurs in Iranian Jewish communities, as well as in other groups worldwide such as in Japan, South Asia, and the Middle East. Initial signs of the disease usually appear in early to mid-adulthood. Both parents must be carriers of the mutation for children to inherit the illness. Individuals are encouraged to undergo confidential genetic screening to assess their risk. Genetic counseling is available for couples to reduce the likelihood of transmission to children.
What can we do?
Despite preventative measures, new cases of GNEM will continue to emerge due to many undiagnosed or misdiagnosed individuals. Patients face worsening symptoms and increased disability. We have a unique opportunity to help advance possible treatment options. With continued support and developments in science and technology, the potential to find disease-modifying treatment is now within reach.
What is NDF?
For nearly a decade, the Neuromuscular Disease Foundation (NDF), an accredited 501(c)(3) nonprofit organization, has been at the forefront of the search for treatments and enhancement of patients’ quality of life. Our website (curegnem.org) is the premier source of information available regarding current scientific progress and patient programs. We have diligently reduced overhead costs while remaining focused on funding the most promising scientific medical research
toward a cure.
What is the most promising progress towards treatment?
We have reached a turning point, as gene therapy technologies have evolved and are being approved for use by the US Food and Drug Administration (FDA) for the treatment of neuromuscular conditions such as Duchenne Muscular Dystrophy and Spinal Muscular Atrophy. This cutting-edge technology uses Adeno-Associated Virus (AAV) vectors to deliver a healthy copy of the disease-causing gene directly to muscle tissue, potentially correcting the root cause of GNEM.
Summary of NDF’s Gene Therapy Efforts
The Neuromuscular Disease Foundation (NDF) has provided millions of dollars in funding for critical research, symposia and other programs with the goal of finding treatments. This effort has continued over the last few years as we conduct foundational studies that are paving the way to an effective gene therapy treatment. NDF’s flagship plan is the International Gene Therapy Development Program (IGTDP) to produce an AAV-mediated gene therapy to treat GNEM.
Over the last 5 years, the IGTDP has made significant advances in the development of gene therapy to treat GNEM. This drug, called GNE-001, acts to deliver a healthy copy of the GNEM gene via a next-generation AAV vector. In November of 2024, the NDF submitted a pre-Investigational New Drug (pre-IND) package to the FDA. The acceptance and completion of a pre-IND with the FDA provides significant regulatory buy-in and alignment ahead of a future clinical trial, helping to de-risk potential regulatory concerns well ahead of time. The completion of the pre-IND was possible thanks to the remarkable progress made over the last year, leading to four major completed milestones that provide steps forward in developing a GNEM gene therapy:
- Determined a suitable mouse model for testing AAV based gene therapy for GNEM. We identified a GNE mouse model harboring a common mutation causing GNEM in patients to be used for gene therapy testing in our studies.
- Established a test to measure AAV GNEM gene therapy activity. Along with the mouse model above, we have developed another test that enables us to measure expression of GNE in a dose-responsive manner.
- Adapted state-of-the-art AAVs for use in GNEM gene therapy. We are utilizing a next-generation AAV for clinical development that is potentially much more effective at avoiding the liver than other AAVs. Too much AAV in the liver can cause serious side effects. This may offer benefits for adult patients with GNEM and potentially improved safety.
- Demonstrated the ability to correct a mouse model which harbors GNEM. We performed head-to-head testing of two gene therapy constructs in mice and were able to produce additional GNE expression, providing important proof-of-concept for our gene therapy effort.
The remaining estimated costs to advance our gene therapy through Phase I/II clinical trials are $4.7 million over three years. Once these studies are completed and the IND is approved by the FDA, we can begin human clinical trials for one of the world’s first GNEM gene therapies. The steps that remain in this effort include:
- Conduct mouse study to determine appropriate dosing for human trials (already funded).
$180,000
- Produce the gene therapy for safety studies, and for the future patient clinical trial
$2,800,000
- Prepare the IND application to the FDA; requires animal safety testing,
$600,000
and preparation of the IND application documents.
$50,000
- Conduct a small Phase I/II clinical trial with patients allowing for larger future trials.
$1,250,000
To develop the FDA-approved human clinical trials and possible treatment, NDF collaborates with many world-renowned experts on rare muscle diseases, GNEM, gene therapy, and the FDA approval process, such as:
- Stella Mitrani-Rosenbaum, PhD – Professor at Hadassah University Medical Center
- Marjan Huizing, PhD – Staff Scientist at National Human Genome Research Institute, National Institutes of Health
- Noah L. Weisleder, PhD – Professor and Department Chair of Molecular and Cellular Biochemistry at University of Kentucky
- Angela Lek, PhD, Chief Research Officer at Muscular Dystrophy Association
- Monkol Lek, PhD, Associate Professor of Genetics, Yale University School of Medicine
- Rich Horgan, MBA, Founder & CEO, Cure Rare Disease, a non-profit biotechnology company whose mission is to disrupt the paradigm of drug development for rare, genetic diseases.
Your past contributions have enabled us to achieve this important milestone. Yet, the next set of costs of launching human clinical trials and gaining FDA approval are high. We continue our efforts to secure grants and alternative funding, despite recent budget cuts to scientific research. Given the rarity of GNEM, support from the affected communities is vital to the continuation of our efforts.
Chances are, someone you love is a carrier or will be impacted. NDF’s gene therapy program is based on rigorous science and offers the best potential for treatment. Your contributions have been essential in getting us this far, and your continued financial support is necessary to fulfill our mission. Please make your tax-deductible contributions using the link below.
We welcome your questions and comments about our gene therapy program at info@curegnem.org. We’ll respond directly and post the anonymized answers to our website FAQ so others can benefit. If you’d like to discuss a contribution, please contact us to schedule a conversation.
