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Press Release – NEURO-BIO ATTRACTS OVER $3 MILLION IN SERIES A INVESTMENT TO DEVELOP A NEW APPROACH TO ALZHEIMER’S DISEASE Click here for the Neuro-Bio press release 17th March

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Neurodegeneration and Alzheimer’s Disease

Neurodegeneration is the progressive loss of neurons which drives a vicious cycle of degradation of brain cells, which in turn leads to the destruction of key brain areas seen in conditions such as Alzheimer’s Disease, Parkinson’s Disease and Motor Neuron Disease.

Over time, the compounded degeneration of neurons in large areas of the brain leads to cognitive impairments such as confusion, disorientation, loss of insight and of memory. In the case of Parkinson’s and Motor Neuron Diseases, movement is severely compromised. Such crippling conditions are devastating for patients as well as for their families and friends, and are a colossal burden on society – hence the huge unmet need to find long-term solutions and remedies to such debilitating diseases to lessen the burden on patients, carers and healthcare systems alike.

Today, dementia, including Alzheimer's Disease which represents 70% of dementias, is one of the biggest global public health challenges facing our generation. Over 35 million people worldwide currently live with the condition and this number is expected to double by 2030 and more than triple by 2050 to 115 million. With the world's population aging rapidly, Alzheimer's Disease alone, as opposed to dementia in general, is expected to boom in the elderly, with the worldwide Alzheimer's Disease patient population expected to swell from 21 million in 2010 to 53 million by 2050.

In the absence of improved treatment options, healthcare costs associated with Alzheimer's Disease and other dementias are high and expected to continue to rise substantially. In the United States alone, Alzheimer's Disease healthcare costs are projected to increase from US$ 200 billion in 2013 to US$ 1.2 trillion by 2050. The total estimated worldwide cost of dementia was US$ 604 billion in 2010.

In response to these challenges, researchers have undergone intense searches for new, more effective, treatments to prevent, cure or modify this devastating disorder. In spite of these efforts, the US Food and Drug Administration has only approved five medications for Alzheimer's Disease and these treat just the symptoms, there have been no new drug approvals for Alzheimer’s Disease for over 12 years.

More effective therapies, such as those addressed by the Neuro-Bio technology, combined with diagnostics and biomarkers to correctly diagnose the ailment and treat the condition in a more timely fashion, will significantly lessen the burden on patients, carers and healthcare systems alike and are urgently required.

General Background

The presence of beta-amyloid has long been linked to the pathogenesis of Alzheimer’s Disease. But despite huge efforts in the pharmaceutical industry beta-amyloid has not proved an effective target for new drug candidates. This suggests that whilst being an important part of the jig-saw the presence of amyloid alone can’t account for how and why neurons embark on the remorseless cycle of death characterising neurodegeneration.

Neuro-Bio can now, for the first time, complete this jig-saw with its’ paradigm-shifting approach by giving a more precise description of the neurodegeneration underlying Alzheimer’s Disease, as well as explaining a range of previous clinical puzzles:

  1. Alzheimer’s Disease frequently occurs as a co-pathology with other conditions such as Parkinson’s Disease.
  2. Amyloid precursor protein is widespread in the brain, but only certain neurons are lost in the early stages of Alzheimer’s Disease with these being in the ‘hub’ at the core of the brain.
  3. The underlying neurodegenerative mechanism perpetuating continued loss of neuronal cells.

Neurodegeneration in Alzheimer’s Disease, Parkinson’s Disease and Motor Neuron Disease doesn’t begin in all neurons. Only certain groups of cells in a ‘hub’ at the core of the brain are initially vulnerable. The key brain cells lost in Alzheimer’s Disease are adjacent to those lost in Parkinson’s Disease, with those associated with Motor Neuron Disease similarly close by, with these all located at the ‘hub’ of the brain (see Figure below).


Figure showing “hub” cells at the core of the brain

A Novel Peptide Increased in Alzheimer’s Brain

The presence of the enzyme acetylcholinesterase (AChE) is characteristic feature of the vulnerable ‘hub’ cells, where it occurs in the absence of its normal substrate and instead is co-localised with a range of different transmitters. This discrepancy suggests an alternative function as an independent signalling molecule that we have now shown in the context of the adult brain shifts from a developmental role to acting as a toxin. We now have direct evidence not only that the peptide exists as an independent biochemical entity but that it has doubled in the Alzheimer brain to a level commensurate with that seen in the developing brain.

The Mechanism Underlying Alzheimer’s Disease

The vulnerable cells forming the ‘hub’ originate from a distinct part of the early embryo brain; the basal plate whereas other brain cells derive from the alar plate. Unlike all other brain cells the ‘hub’ cells retain sensitivity to developmental chemicals usually only released, and beneficial, in the developing brain (see Figure below). When compared to developing foetal/neonatal brain cells, mature, adult brain cells respond differently to the same developmental chemicals, which if released inappropriately in maturity as a result of brain damage in the different, mature brain landscape, are toxic causing cell death instead of assisting in brain cell development (see Figure below). This brain cell damage causes additional release of the now toxic chemical in the mature brain and the relentless cycle of neurodegeneration (see Figure below).

Figure that illustrates the cascade of actions that begin the cycle of cell death in the ‘hub’ neurons and subsequently further brain cell death along with the production of beta-amyloid and tau. This scheme also accounts for the selective cell death that occurs in Alzheimer’s Disease. The neonatal young brain is characterised by the ability to be shaped by various growth factors. However, once mature, most of the standard brain cells lose their sensitivity to these chemicals. If they are damaged, as in a stroke, some die whilst other compensate, leading to partial or complete recovery of function.

At first this pernicious cycle continues without detectable symptoms but eventually cell loss in the ‘hub’ neurons becomes extensive and their normal target areas in the cortex begin to show effects of depravation of normal active input (trans-synaptic degeneration). Cognitive impairments will be manifest and more widespread physical damage finally becomes apparent as neurons die (see Figure below).

By building on its’ unique insight into the underlying mechanism triggering neurodegeneration Neuro-Bio can offer a first-of-its-kind solution to effectively treat neurodegenerative conditions such as Alzheimer’s Disease, Parkinson's Disease and Motor Neuron disease.

The Company has developed an innovative method with the potential to intercept and halt action of the toxic AChE-peptide on the receptor to arrest further cell death. By using a range of novel molecules the Company has designed based on the active part of the AChE-peptide the Company has shown that the action of the toxic molecule can be blocked and the neurodegenerative cycle halted. The company is working with a number of these Intellectual-Property protected, novel agents and will be seeking for commercial partners to progress these through the drug development process.