NBP14, a new drug candidate from Neuro-Bio Ltd., effectively treats the signs of neurodegeneration in a mouse model of Alzheimer’s disease, according to a paper published in the journal Alzheimer’s & Dementia: Translational Research & Clinical Interventions.
The T14 system participates in at least four interactive cascades. Image credit: Greenfield et al., doi: 10.1002/trc2.12274.
The basic mechanism driving Alzheimer’s disease, as well as Parkinson disease and motor neuron disease, may be the deleterious activation in the maturity of a signaling system that had been beneficial in development.
Toxic effects may occur if this system is activated in the mature brain in response to a blow to the head, ischemia, or a decline in scavenging mechanisms.
Such a phenomenon would exemplify antagonistic pleiotropy, as proposed in George Williams’ evolutionary explanation of senescence.
His theory concerns tradeoffs between early life benefits and late-life detriments and is consistent with a decline in the potency of natural selection with age.
The signaling molecule driving this particular process is posited to be a peptide called T14.
“By using basic neuroscientific knowledge we have identified what we believe is an underlying mechanism driving Alzheimer’s disease in the brain, and have developed a molecule — NBP14, a cyclic version of T14 — to combat it,” said Baroness Professor Susan Greenfield, founder and CEO of Neuro-Bio Ltd.
“Our recent efficacy study in mouse models further validates previous work describing an erstwhile unidentified process in neurodegeneration and offers very exciting prospects for treating the disease in humans.”
“This research should help position the drug intercepting this process, NBP14, for human clinical trials and hopefully create an entirely new era of Alzheimer’s therapeutics.”
“The results consistently indicate that NBP14 might interfere with the neurotoxic process that leads to neuronal degeneration in Alzheimer’s,” added Professor Paul Herrling, former global head of research of Novartis Pharma and non-executive director at Neuro-Bio Ltd.
“This work has very exciting implications for treating Alzheimer’s because it is based on a strong scientific theory that hasn’t yet been applied to treatment of the disease.”
Inactivation of T14 could potentially serve as a treatment for Alzheimer’s by halting the early advance of cell damage occurring first in primarily vulnerable cells deep the brain.
Initially identified by the neurologist Martin Rossor back in 1981, these primarily vulnerable cells form a kind of central hub in the brain, extending up from the top of the spinal cord. A key feature is that they are the first to display a pathology early in neurodegeneration.
The study authors believe that detection and measurement of T14 could be developed as a blood test or skin biopsy to identify the occurrence of the degenerative process during the window of ten to twenty years that typically occurs before symptoms start.
If NBP14 proves effective in human trials, it could become a routine, home-administered nasal spray to halt neurodegeneration before any symptoms appear.
No harmful side effects at the active dose in the disease model were observed with NBP14 during the efficacy study.
The researchers now plan to take the drug to clinical Phase I trials as soon as possible.
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Susan A. Greenfield et al. A novel process driving Alzheimer’s disease validated in a mouse model: Therapeutic potential. Alzheimer’s & Dementia: Translational Research & Clinical Interventions 8 (1): e12274; doi: 10.1002/trc2.12274
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