A groundbreaking basket clinical trial focused on a pair of rare mitochondrial diseases has reached a pivotal milestone, with its official registration on ClinicalTrials.gov. The trial, titled Investigational Study of Glycerol Tributyrate on MELAS and LHON-Plus, is led by Anne Chiaramello, PhD, professor of anatomy and cell biology at the George Washington University School of Medicine and Health Sciences (GW SMHS).
Joining Chiaramello, who also serves as principal investigator and founding director the Mito-EpiGen Program at GW SMHS, is Debra Regier, MD, PhD, medical director of the Children’s National Hospital Rare Disease Institute, and Wei-Liang Chen, MD, an assistant professor specializing in pediatric neurology and neurogenetics. The study, funded by the National Institute of Health's National Center for Advancing Translational Sciences, will evaluate whether a therapeutic candidate, glycerol tributyrate, can target the shared molecular causes underlying two mitochondrial diseases: MELAS (mitochondrial encephalopathy, lactic acidosis, stroke-like episodes) and LHON-Plus (Leber’s hereditary optic neuropathy-Plus).
This milestone in the clinical trial process is significant not only for the scientific community, but also for the patients who suffer from these often-debilitating conditions. The trial, now officially listed on National Institutes of Health database, underscores the importance of transparency and scientific integrity in medical research. The site serves as a valuable resource for researchers, health care professionals, and the public, providing easy access to information about ongoing and completed clinical trials, and ensuring that all relevant trials are accessible and transparent.
“This first basket clinical trial on MELAS and LHON-Plus will provide the blueprint for other rare mitochondrial diseases, a strategy that will be beneficial to many patients by adapting our personalized medicine-based approach,” said Chiaramello.
Through the trial, Chiaramello and her team will enroll 24 patients, with 12 participants from each disease group, to undergo a 6-month personalization phase where drug dosages will be tailored to individual patients, followed by a 12-month treatment phase. Researchers will assess mitochondrial energy signatures in patient-derived samples with the goal of improving energy levels and clinical symptoms, such as mobility, cognitive function, and organ performance.
“The ability to personalize treatment in these rare diseases could be transformative for patients, offering them hope where there has previously been little,” Chiaramello said.
Recruiting patients for such rare diseases is a daunting task, and Chiaramello has worked to establish partnerships with patient advocacy groups, such as the U.S.-based LHON-Plus-Action and the Canadian-based LHON-Plus Global, to connect with qualifying patients and their families and ensure the trial’s success.
MELAS and LHON-Plus, both mitochondrial disorders passed from mother to child, have a devastating impact on those who are diagnosed. MELAS typically begins in childhood, while LHON-Plus often manifests in early adulthood. Patients experience a range of debilitating symptoms including seizures, migraines, cognitive impairment, muscle weakness, and vision loss. Because both diseases affect the body’s energy production — particularly in high-demand organs such as the brain, muscles, and heart — the symptoms can be particularly devastating for affected individuals and their families and care givers.
Currently, treatment options for these diseases are limited, with most therapies offering only palliative care that does little to slow the fatal progression of the conditions. The success of this trial could pave the way for better therapeutic strategies, potentially improving the quality of life for individuals with these rare mitochondrial disorders.
“For patients with LHON-Plus or MELAS, treatments are as rare as the disease itself. Therefore, they are key partners to overcome the numerous challenges of developing a pharmacological treatment independently of industry partners,” said Chiaramello, adding, “these patients deserve to have a bright light [shone] on their diseases.”
