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.
https://hotcopper.com.au/threads/ann-neuren-advances-nnz-2591-towards-ind-application.2336223/
In a patent granted in the US in 2014, claim was made for use of NNZ-2591 to relieve or alleviate a symptom of cognitive impairment caused by:
disease - Alzheimer’s disease, Huntington’s disease, Lewy Body disease, dementia, cerebral atrophy, frontotemporal lobar degeneration, Pick’s disease, multi-infarct dementia, HIV infection, and Down’s syndrome
injury - neurotoxic injury, cerebral hypoxia/ischemia, traumatic brain injury, coronary artery bypass surgery
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.
https://patentscope.wipo.int/search/en/detail.jsf?docId=US73327646&_cid=P10-LFKB8C-51785-4
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.
https://patentscope.wipo.int/search/en/detail.jsf?docId=US191715060&_cid=P10-LFKB8C-51785-4
More recently, a patent application has been filed for use of NNZ-2591 in Pitt Hopkins Syndrome.
https://patentscope.wipo.int/search/en/detail.jsf?docId=US380601177&_cid=P10-LFKBKE-55250-1
Even more recently, an international patent application has been filed for use of NNZ-2591 in treating Prader-Willi Syndrome.
https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2022173315&_cid=P10-LFKBKE-55250-1
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:
Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, traumatic brain injury, multiple sclerosis, ischaemic stroke, Tuberous Sclerosis Complex, mood disorders and depression, diabetes, seizure activity, ALS (Lou Gehrig’s disease), Frontotemporal Dementia, Progressive Supranuclear Palsy, sepsis-associated encephalopathy, Charcot-Marie Tooth disease, Prion disease, Vanishing White Matter Disease, Pelizaeus-Merzbacher Disease, Graves’ orbitopathy and cancer.
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”.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542591/
https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.14422
https://www.mdpi.com/2218-273X/11/3/354
https://www.cambridge.org/core/jour...ease-control/E0C46CE96B64AED803C9B9F162F141C5
https://www.proquest.com/openview/b...a3dbe1/1?pq-origsite=gscholar&cbl=4424410
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