Mitochondrial encephalomyopathy, lactic acidosis, and stroke like episodes (MELAS) is a genetic disorder of the mitochondria and tends to appear before the age of 20. It is a mitochondrial disease that affects the function and development of the brain; causing neurological impairment, lowers oxygen levels in the blood and leads to seizures. Defining symptoms are stroke-like episodes causing vomiting, headache, fatigue and weakness.

Currently there are no approved drugs for the treatment of MELAS, it is an unmet clinical need. MELAS is the most common of the mitochondrial diseases, with approximately 1/10,000 people affected (https://www.orpha.net), the estimated prevalence in the US is 30,000 patients.

Rett syndrome (RS) is a neurodevelopmental disorder that affects mostly young girls. It is caused by a mutation in the MECP2 gene, that is critical in the development of the brain. Symptoms from RS includes, slowed growth, loss of motor skills, loss of communication abilities, seizures; however, its most distinguishing symptom is noticeable abnormal hand movements.

There is no approved treatment for RS in Europe, therapies available are typically for the treatment of symptoms. A key trait in RS patients is the down regulation of Brain Derived Neurotropic Factor (BDNF). BDNF is a protein that creates nerve cells, aids in their survival and creates synapses important in the connections and communications between cells. Prevalence of RS in Europe is 1/10,000 girls and is estimated at 25,000 girls (https://www.ema.europa.eu).

Non-alcoholic fatty liver disease (NAFLD) is condition that occurs when there is a build-up of fat in the liver. When NAFLD progresses to non-alcoholic steatohepatitis (NASH) there is inflammation of the liver and liver damage, often leading to cirrhosis (where the liver is scarred permanently). Cirrhosis may lead to liver cancer or liver failure with the need for a transplant. There are currently no approved drugs for NASH.

There are links between the healthy mitochondria and NASH showing that potential interventions that target the thiol/disulfide balance and mitochondrial health would have a clinical benefit on NASH. In addition, there are potential benefits in NASH from increasing exposure to anti-oxidants and anti-inflammatories.

Based on cysteamine’s decades long history as a safe pediatric drug, treating children with cystinosis, Thiogenesis is targeting the unmet medical need of pediatric NASH as its initial indication in liver disease. There are an estimated 7 million children with pediatric NASH in the US (https://www.international-nash-day.com).