Neuren Media and Analyst Coverage, page-1704

And how many syndromes does that (NNZ-2591) work on?

So, we have had positive phase 2 results in three, Phelan-McDermid syndrome, Angelman syndrome and Pitt Hopkins syndrome. But we don't think that's the end of the story, because of the way it works and this commonality across these things.

This is a perfect segue into something I've been recently researching...

According to the World Health Organization, approximately 1 in 100 children worldwide has autism (ASD).

The rate is higher in the United States and has been increasing. The most recent research published by the CDC suggests the prevalence of ASD in the United States is 1 in 31 children. Boys are 3 to 4 times likely to be diagnosed with ASD than girls.

No single cause has been found for ASD.

Somewhere between 10% - 20% of ASD cases are linked to a specific genetic mutation. These cases are sometimes referred to as monogenic autism spectrum disorders or syndromic autism, although there is a lack of agreement on the desirability and accuracy of these terms. The origin of the other 80%-90% of ASD cases is unknown; these cases are referred to as idiopathic autism.

In a recently published paper, Visegrady hypothesizes that idiopathic autism features biphasic postnatal dysregulation of IGF-1. During the phase from birth to approximately 12-15 months, excess IGF-1 is produced, leading to somatic and brain overgrowth. It is proposed that the excess IGF-1 spurt during this phase might lead to irreversible structural connectivity abnormalities specific to ASD. An abrupt drop in IGF-1 levels marks the next phase (see table below). The author proposes that CSF IGF-1 levels could be tested in at-risk neonates 3–6 months old in order to test the hypothesis of early elevated levels, and that confirmation of his hypothesis could support effective early prevention initiatives.



NNZ-2591 (cG-2-AllylP) is currently being developed in multiple monogenic disorders that have overlaps with autism and in neonatal hypoxic-ischemic encephalopathy (HIE). In HIE and some of these monogenic disorders, there are depressed levels of IGF-1 in the brain.

NNZ-2591 is believed to regulate IGF-1 homeostasis, that is, it promotes the activity of IGF-1 when it is insufficient, but inhibits the activity of IGF-1 when it is excessive.

If this fascinating hypothesis of biphasic postnatal dysregulation of IGF-1 occurring in idiopathic ASD is proven to be correct, NNZ-2591 would seem to be an ideal therapeutic intervention.