FDA Grants Orphan Drug Designation to NSI-189 for Treatment of Angelman Syndrome

The US Food and Drug Administration (FDA) has decided to grant an orphan drug designation to Neuralstem, Inc.’s NSI-189 for the treatment of Angelman syndrome, a rare congenital genetic disorder caused by a lack of function in the UBE3A gene located on the maternal 15th chromosome.

“Angelman Syndrome is a rare disease with significant unmet need, and for which there are no FDA-approved therapies,” Jim Scully, Neuralstem’s chief executive officer, commented in a recent statement. “Orphan drug designation is an important regulatory milestone in the development of NSI-189 and we are committed to evaluating NSI-189’s role as a treatment to improve the lives of patients with Angelman syndrome."

NSI-189 is Neuralstem’s lead compound and it’s under development not only for Angelman syndrome, but also for major depressive disorder, and other psychiatric and/or cognitive impairment indications linked with hippocampal atrophy.

In preclinical models, the drug was found to be capable of restoring long-term potentiation—a measure of synaptic plasticity and an in vitro biomarker of memory. NSI-189-induced LTP requires protein synthesis, according to Neuralstem, which suggests structural synaptic plasticity.

When used in brain slices from mice with a genetic defect similar to Angelman syndrome, NSI-189 was found to restore LTP to normal levels, according to the biopharmaceutical company. The treatment was also found to improve behavioral and memory function as well as to preserve hippocampal neurogenesis in a rat model of irradiation-induced cognitive impairment.

Angelman syndrome is estimated to affect about 1 in 15 000 individuals, about 500 000 individuals worldwide. Life expectancy for those with the disorder is normal, but the symptoms are debilitating; as such, many individuals require life-long care. Individuals with Angelman syndrome can experience developmental delay, lack of speech, seizures, and walking and balance disorder, sometimes so severe that they may never walk or speak again.