Barth Syndrome (BTHS) Clinical Trials and Treatments

Barth syndrome is caused by pathogenic variants in TAFAZZIN (formerly TAZ), located on the X chromosome. TAFAZZIN encodes a transacylase enzyme on the inner mitochondrial membrane that remodels cardiolipin, a phospholipid found almost exclusively in mitochondria. Mature, properly remodeled cardiolipin is essential for assembly and function of the electron transport chain, the molecular machinery that produces cellular energy (ATP).

The most common symptoms of Barth Syndrome include Cardiomyopathy (dilated, hypertrophic, or with left ventricular noncompaction) — often the presenting feature in infancy, Neutropenia (low neutrophil count) that may be chronic, cyclic, or intermittent and increases serious infection risk, Skeletal muscle weakness, especially in proximal limb muscles, Severe exercise intolerance and disabling fatigue, Growth delay and short stature, often falling below the 5th percentile, among others. Estimated at 1 in 300,000 to 1 in 400,000 live births in the United States. Stealth BioTherapeutics, now Mighty Therapeutics, said at the 2025 approval that about 150 people in the U.S. have Barth syndrome. A 2020 study by Miller and colleagues in the Journal of Pediatrics counted 230 to 250 known cases worldwide and concluded the disease is greatly underdiagnosed. Symptoms can range from mild to severe and may vary between individuals.

Trial Friend lists all active clinical trials for Barth Syndrome from ClinicalTrials.gov, with eligibility criteria translated into plain English. Patients can filter by trial phase and recruitment status, search by location, and use the Match Me tool to score trials against their profile. On September 19, 2025, the FDA granted accelerated approval to Forzinity (elamipretide) to improve muscle strength in adult and pediatric patients with Barth syndrome who weigh at least 30 kilograms (about 66 pounds). The approval is based on data from the open-label portion of the TAZPOWER trial, which showed improvements in knee extensor muscle strength from baseline.

On September 19, 2025, the FDA granted accelerated approval to Forzinity (elamipretide) to improve muscle strength in adult and pediatric Barth syndrome patients weighing at least 30 kilograms (about 66 pounds). Forzinity is a once-daily under-the-skin injection of a small peptide that binds and stabilizes cardiolipin in the inner mitochondrial membrane, supporting the energy-making machinery despite the underlying TAFAZZIN problem. It is the first FDA-approved therapy specifically for Barth syndrome, and the company describes it as the first FDA-approved mitochondria-targeted therapeutic. Because this is an accelerated approval, continued FDA approval may depend on a confirmatory trial, 4TAZPower (NCT07531251), which began recruiting in July 2026. Mighty Therapeutics (formerly Stealth BioTherapeutics) said at approval that it would continue compassionate use access for patients under 30kg while working with the FDA to broaden the indication. Supportive care in Barth syndrome includes heart failure pills (ACE inhibitors, beta blockers, mineralocorticoid receptor antagonists), G-CSF (filgrastim or pegfilgrastim, drugs that boost neutrophil counts) for severe neutropenia, prophylactic antibiotics during high-risk periods, nutritional support, and physical therapy. Heart transplant is performed in selected severe cases.

Barth syndrome is caused by mutations in the TAFAZZIN gene (formerly called TAZ) on the X chromosome, which makes a mitochondrial enzyme called tafazzin. Mitochondria are the energy factories inside every cell. Tafazzin remodels cardiolipin — a membrane fat found almost exclusively inside mitochondria and essential for the energy-production machinery to work properly. When tafazzin is missing or broken, cardiolipin gets stuck in an immature form (called monolysocardiolipin, or MLCL), which makes mitochondrial membranes unstable and reduces ATP, the cell's energy currency. The tissues that depend most on aerobic energy show the effects first: the heart muscle (cardiomyopathy, sometimes with a feature called left ventricular noncompaction where the muscle wall is incompletely formed), skeletal muscle (proximal weakness and exercise intolerance), and white blood cells (chronic, cyclic, or intermittent neutropenia, meaning a low count of infection-fighting cells). Because TAFAZZIN sits on the X chromosome, almost all affected individuals are male; mothers and sisters of affected boys are usually carriers. The blood-test fingerprint of the disease is an elevated MLCL-to-cardiolipin (MLCL:CL) ratio.

TAFAZZIN gene sequencing is the definitive diagnostic test for Barth syndrome and is required for enrollment in most clinical trials. Over 250 different disease-causing variants have been reported across all coding parts of the gene, including missense, nonsense, frameshift, splice-site, and deletion variants. The diagnostic blood test is the MLCL:CL ratio (monolysocardiolipin to mature cardiolipin) — highly sensitive and specific for Barth syndrome. 3-methylglutaconic aciduria on a urine organic-acid test is a non-specific but commonly seen marker (a substance that builds up in urine when mitochondria are not working right). Because Barth is X-linked, female carriers — mothers and sisters of affected boys — are usually symptom-free but have a 50 percent chance of passing the mutation to each son. Cascade genetic testing and counseling for at-risk female relatives is recommended. Labs offering TAFAZZIN testing and MLCL:CL ratio analysis include GeneDx, Invitae, PreventionGenetics, and the Barth Syndrome Foundation's clinical lab partners.

Eligibility for Barth Syndrome clinical trials depends on factors like age, diagnosis, treatment history, and overall health. Each trial sets its own inclusion and exclusion criteria. Trial Friend translates these requirements from medical language into plain English so patients can review them more easily. The Match Me tool can score your profile against active trials to help identify studies that may be a fit.

Participating in a Barth Syndrome clinical trial typically involves scheduled visits, medical tests, and close monitoring by a research team. Depending on the study phase, you may receive an investigational treatment, a placebo, or the current standard of care. Trials may last from a few weeks to several years. Study participation is voluntary, and you can withdraw at any time.

Barth syndrome clinical trials commonly require stable cardiac and supportive medications for 2 to 3 months before enrollment but typically allow continuation. Trials of new mitochondrial therapies may exclude prior elamipretide (Forzinity) exposure or require a multi-week washout. Gene therapy trials would exclude any prior gene therapy. G-CSF (filgrastim, pegfilgrastim) for low neutrophil counts is usually allowed if the regimen is stable. Investigational agent washout periods range from 30 to 90 days. Trial Friend's medication conflict checker scans each trial's exclusion criteria against common Barth medications including elamipretide, ACE inhibitors, beta blockers, diuretics (water pills), mineralocorticoid receptor antagonists, G-CSF, prophylactic antibiotics, and investigational agents. The checker flags the specific drug, the trial's exclusion language, and a confidence level so you can discuss timing with your cardiologist or metabolic specialist.

Key questions to ask your cardiologist or metabolic specialist about Barth syndrome: My child weighs less than 30kg (about 66 pounds), the on-label cutoff for Forzinity. Can we ask Mighty Therapeutics (formerly Stealth BioTherapeutics) about its compassionate use access for children under 30kg? Can you walk me through my child's most recent heart numbers, the LVEF (how strongly the heart pumps), fractional shortening, and the peak VO2 (oxygen used during exercise), and how they have changed over time? How is knee extensor muscle strength being measured at follow-up, since that was the FDA-approved measure of whether the drug is working? My child's MLCL:CL ratio and absolute neutrophil count (ANC) have varied. Should we change how often these are checked, or start G-CSF at a different threshold? At what point would heart transplant evaluation be appropriate? Should my mother and sisters be tested for the TAFAZZIN gene mutation, given the 50 percent chance of passing it to each future son?