Neonatal encephalopathy (NE) following Birth Asphyxia (i.e. severe oxygen deprivation at birth) is one of the leading causes of neonatal death and adverse long-term neuromotor outcome in near term infants worldwide, resulting in cerebral palsy, mental retardation, visual impairments and epilepsy. The overall burden of NE is very high: about 2% of the total global burden of disease is being caused by NE, resulting not only in about 1 million deaths worldwide, but has also a big impact on patients, families and society involved. Healthcare cost per life amount to 1 million USD in the western world.
The only treatment proven to effectively reduce the sequelae of NE in the western world is the application of therapeutic hypothermia (TH, cooling) with about 15%. During TH the temperature is lowered to 33-34C for 72 h. Despite this treatment 45% of the neonates still has a bad outcome after 2 years. No pharmaceutical therapy is available today.
Each year, over half a million persons experience an out-of-hospital Cardiac Arrest (OHCA). This number is growing due to increasing obesity and lifestyle. Approximately 50% of OHCA-patients have sustained return of spontaneous circulation, but despite decades of research, median reported rates of survival to hospital discharge are poor (7,8%) and remained virtually unchanged for the past 30 years.
In survivors of Cardiac Arrest long neurologic deficits, mainly cognitive defects, are present in 30 to 50% of patients, making Cardiac Arrest a large problem with an unmet medical need. Current treatment is temperature targeted management (TTM), in which the patient's temperature is maintained stable at 36C mainly for 24 h. Effectivity of this treatment in comparision to the prevention of hyperthermia needs to be proven. No pharmaceutical therapy is available today.
The problem: Reperfusion damage
Hypoxia-ischema is not a single event but a biphasic process that leads to significant neuronal cell death over hours to days after initial hypoxic-ischemic insult (reperfusion damage). Neuroprotective treatment can be given within the therapeutic window, the first 6 hours after Cardiac Arrest as wel as Birth Asphyxia, to reduce the reperfusion damage in the brain and improve long term outcome.
The solution: 2-iminobiotin
The neuroprotective effects of 2-iminobiotin, a selective inhibitor of neuronal and inducible nitric oxide synthase, have been well established in preclinical trial in 4 animal models. An excellent safety profile has been found in both clinical trials in adults after Cardiac Arrest and in newborns after Birth Asphyxia. First signs of efficacy have been seen in clinical trials. 2-IB is expected to double the efficacy compared to TH/TTM.
At this moment Neurophyxia is raising funds for a large phase 2b/3 clinical trial to determine efficacy in neonates after birth asphyxia in low-income countries.
For further evaluation of efficacy and distribution of 2-IB, the Foundation Saving Babies’ Lives in low-income countries has been founded. For more information, see www.savingbabieslives.nl