The suggestion of 40 possible indications for NNZ-2591 also set me thinking. I decided to track down those already identified.
Early research into NNZ-2591 showed positive results in well-validated preclinical models of Parkinson’s disease, stroke, traumatic brain injury, peripheral neuropathy, Fragile X Syndrome, memory impairment, relapsing-remitting multiple sclerosis and progressive multiple sclerosis.
condition - normal aging, age-related memory loss, memory impairment, cholinergic hypofunction, vascular narrowing or blockage in the brain, neuroinflammation, mild cognitive impairment and loss of synaptic plasticity.
In a further patent granted in the US in 2018, claim was made for use of NNZ-2591 in treating a symptom of an Autism Spectrum Disorder (ASD) or Neurodevelopmental Disorder (NDD) selected from the group:
Asperger Syndrome, Childhood Disintegrative Disorder and Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS), Pathological Demand Avoidance (PDA), Fragile X Syndrome (FXS), Angelman Syndrome, Tuberous Sclerosis Complex, Phelan McDermid Syndrome, Rett Syndrome, CDKL5 mutations, and X-Linked Infantile Spasm Disorder.
So there are almost 40 potential indications for NNZ-2591 that have already been identified by Neuren, encompassing various neurodevelopmental and neurodegenerative diseases and injuries and conditions impacting the brain. These indications range from low prevalence (orphan disease) to high prevalence.
I wondered if there might be more.
Neuren has stated that in biochemical testing, NNZ-2591 was shown to normalise the abnormal length of dendrite spines between brain cells, the excess activated ERK protein (pERK) and the depressed level of IGF-1 in shank3 knockout mice.
I’ve underlined the section on pERK, because, while we’ve heard a lot already about both NNZ-2566 and NNZ-2591 normalizing IGF-1 levels and dendritic length, little has been said about pERK. So I thought I’d do a brief search of the literature.
What’s clear is that ERK overactivation causes neuropathological changes seen in brain diseases. pERK dysregulation has been identified in multiple diseases and conditions. The authors of one paper even coined the term “PERK-opathies”(see 1st link below) for various neurodegenerative diseases in which pERK plays a crucial role.
I’ve compiled a list below of some diseases/conditions in which pERK dysregulation is seen, highlighting those not already mentioned above:
When you also consider that Neuren has stated that NNZ-2591 has valuable pharmaceutical attributes, including higher oral bioavailability (approximately 100%), improved stability and potential for a solid oral dosage form, then Neuren would appear to be in possession of a highly versatile and valuable drug molecule.
No wonder Jon Pilcher has consistently described NNZ-2591 as Neuren's “ jewel in the crown”.
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