Ronopterin is an allosteric inhibitor of inducible NO synthase (iNOS) that rapidly decreases the excessive production of NO resulting from acute overactivation of this enzyme. Ronopterin has no significant effect on the physiological production of NO by other constitutive NO-synthesizing enzymes that are essential for brain and body function.
Since several cerebral diseases such as head trauma, stroke, retinal degeneration, and glioblastoma-induced secondary damage are associated with upregulation of i-NOS and cytotoxic edema formation, Ronopterin is an ideal drug to help patients suffering from these diseases.
This benefit has already been demonstrated in patients suffering from a Traumatic Brain Injury who received Ronopterin within 12 hours of injury. These patients showed improved neurological recovery, measured 6 months after treatment with the extended Glasgow Outcome Score. Patients treated with Ronopterin also presented a higher quality-of-life index 6 months after injury. Patients in the standard treatment group who did not receive Ronopterin required more aggressive interventions (measured by Therapy Intensity Level) in the first 14 days after injury with significantly higher cerebral glutamate levels during this phase. In general, excessive extracellular glutamate levels in patients' brains have deleterious effects on the function of cerebral cell structures.
It is also known that pathophysiological elevated glutamate triggers cytotoxic edema, which is a key element of retinal degenerative processes, glioblastoma-induced secondary damage, and also stroke pathophysiology.
Consequently, the potential of Ronopterin wil be further investigated in appropriate preclinical models to prepare the ground for further clinical trials in patients suffering from glioblastoma and diabetes-related retinopathy.