The U.S. Food and Drug Administration (FDA) has designated NSI-189 an orphan drug to help advance Neuralstem’s lead compound in development as a potential treatment of Angelman syndrome.

Angleman “is a rare disease with significant unmet medical need, and for which there are no FDA-approved therapies,” Jim Scully, the company’s chief executive officer, said in a press release. “Orphan drug designation is an important regulatory milestone … and we are committed to evaluating NSI-189’s role as a treatment to improve the lives of patients.”

NSI-189 is small molecule in clinical testing to possibly treat major depressive disorder (NCT02724735, NCT02695472), and in preclinical development for Angelman, irradiation-induced cognitive impairment, type 1 and type 2 diabetes, and stroke.

Preclinical studies in animal models of Angelman syndrome have shown it works to alleviate cognitive disabilities and nerve cell defects.

Brain slices from healthy mice showed that NSI-189 restored long-term potentiation (LTP), a measure of synaptic plasticity that is associated with memory. Synapses are the junctions between nerve cells that allow them to communicate, and synaptic plasticity refers to the ability of the brain to change and adapt to new information.

In a rat model of induced cognitive impairment, NSI-189 treatment improved behaviour and preserved the production of new nerve cells — called neurogenesis — in the hippocampus, a major brain region involved in memory.

Neuralstem believes NSI-189’s activity stems from its ability to stimulate the formation of new synapses between nerve cells, or the production of new nerve cells.

Orphan drug status is given by the FDA to encourage the development of therapies for rare diseases — those affecting fewer than 200,000 people in the U.S. This designation can help to facilitate the development of a candidate like NSI-189 by providing support during clinical development, and possibly offering marketing exclusivity for a number of years upon regulatory approval.

Angelman, a rare congenital genetic disorder, is marked by developmental delay, lack of speech, seizures, and walking and balance disorders.