Clinical program




Clinical Program


Familial dysautonomia (FD) [MIM#2239001), also known as Riley Day syndrome or Hereditary Sensory and Autonomic Neuropathy III (HSAN-III) is characterized by widespread sensory and variable autonomic dysfunction associated with progressive degeneration of the sensory and autonomic nerves. In FD mice neuronal mitochondria have abnormal membrane potentials, produce elevated levels of reactive oxygen species, are fragmented, and do not aggregate normally at axonal branch points. Our lead compound improved mitochondrial function, protected neurons from dying in vitro and in vivo, and promoted cardiac innervations in vivo. Given that impairment of mitochondrial function is a common pathological component of neurodegenerative diseases, our findings identify a therapeutic approach that may have efficacy in multiple degenerative conditions.


Ventilation-induced diaphragm dysfunction (VIDD) is a marked decline in diaphragm function in response to mechanical ventilation, which has negative consequences on individual patients’ quality of life and for the health care system. Weaning from mechanical ventilation is a time-consuming process, comprising ~40% of the time spent on the ventilator.  Additional problems in weaning are observed in 20-30% of these patients due to VIDD, resulting in prolonged intensive care and support accounting for ~30% of overall ICU costs or a staggering €25 billion in the EU and $48 billion in the US annually. Our lead compound greatly improved diaphragm muscle fiber function in experimental intensive care unit models (by about 100%). The treatment also provided protection from myosin posttranslational modifications associated with HSP72 induction and PARP-1 inhibition, improvement of mitochondrial function and content.


Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Approximately two thirds of COVID-19 patients who require critical care had mechanical ventilation within 24 hours of admission. In vivo preclinical evidence suggests that our lead compound might reduce the risk of complications of COVID-19, as it alleviates the symptoms of mechanical ventilation-induced diaphragm dysfunction, protects against ischemia/reperfusion induced organ damage in heart, kidney and brain, significantly increased the survival of chronic mechanically ventilated rats, may slow down the development of septic shock and may reduce time COVID-19 patients need to stay on the ventilation thus could free up ventilators for other patients.