Neuren Pharmaceuticals (ASX: NEU) has revealed positive pre-clinical results for its NNZ-2591 drug candidate in treating Pitt Hopkins and Angelman syndromes.
According to Neuren, its NNZ-2591 drug is a synthetic analogue of the neurotrophic peptide cyclic glycine proline, which occurs naturally in the brain.
In addition to having a positive effect on Pitt Hopkins and Angelman, Neuren has also demonstrated the drug’s efficacy in pre-clinical models of Parkinson’s disease, stroke, traumatic brain injury, peripheral neuropathy, Fragile X, Phelan-McDermid, memory impairment and multiple sclerosis.
Pitt Hopkins syndrome
Pitt Hopkins syndrome is a neurodevelopment condition in males and females and is caused by the loss of one copy or a mutation of the TCF4 gene on chromosome 18.
The syndrome is characterised by developmental delays with moderate to severe intellectual disability, behavioural differences, hyperventilation, breath holding, seizures, lack of speech, sleep disturbance, gastrointestinal issues, distinctive facial features and stereotypic hand movements.
In this latest pre-clinical test, NNZ-2591 was trialled in the TCF4 mutation mouse model, which exhibits features of Pitt Hopkins in humans.
Normal mice were compared to those with a disrupted TCF4 gene, and it was found after six weeks, NNZ-2591 normalised the deficits in all the tests of hyperactivity, daily living, learning and memory, sociability, motor performance and stereotypy.
“All positive confirmatory measures were statistically significant,” the company stated.
Also a neurodevelopment condition, Angelman syndrome is believed to affect one in 15,000 people and both males and females.
The condition is caused by a deletion or mutation in the ubiquitin protein ligase E3A gene on chromosome 15.
Similar to Pitt Hopkins, the syndrome is characterised by delayed development with intellectual disability, anxiety and hyperactivity, speech impairment, movement and balance problems, seizures and sleep disorders.
The pre-clinical study comprised testing NNZ-2591 on mice with mutated or deleted UBE3A for six weeks.
After the six-week period, the mice were found to have normalised anxiety, daily living, sociability, motor performance, cognition and an absence of seizures.
Orphan drug designation
The results of these latest pre-clinical tests and the recent Phelan-McDermid syndrome study indicate to Neuren that NNZ-2591 meets the criteria for orphan drug designation in treating these conditions.
“We are excited that NNZ-2591 has clearly demonstrated positive and wide-ranging effects in all three of these disorders,” Neuren executive chairman Richard Treagus said.
“These promising results further confirm the potential of this unique neurotrophic drug across a number of neurodegenerative and neurodevelopmental conditions.”
Mr Treagus added the company had focused on disorders where there is a high unmet need and which NNZ-2591 will have the greatest impact on patient outcomes.
“These disorders can often be misdiagnosed as autism and can also be co-diagnosed with autism.”
“Each of them is caused by a mutation or deletion in a specific gene or chromosomal region; however, typically they share many common symptoms and an underlying impairment in the connections and signalling between individual brain cells.”
“Restoring the normal connectivity and signalling between brain cells is considered to be a central property of NNZ-2591,” Mr Treagus explained.
Neuren is currently expediting the remaining tasks to jump to phase two clinical studies with NNZ-2591.
These include manufacturing, toxicity studies and a phase one clinical trial.
“We are targeting filing an investigational new drug application with the US Food and Drug Administration and commencing phase two studies in the second half of 2020,” Mr Treagus added.
By late afternoon, Neuren’s share price was up 14.56% to $1.18.