Auckland Uniservices Limited

Neuronz Limited

Tru-test Corporation Limited

Other

Neuren Pharmaceuticals Limited

Christopher E Williams

Peter David Gluckman

Jian Guan

Mark I Gunning

Ross Graham Clark

Rita V M Krishnamurthi

Arjan Scheepens

The invention relates to neuroprotection and to medicaments for use therein. Neuroprotection is induced by activation of neural growth hormone receptors, primarily using medicaments comprising growth hormone, growth hormone analogs or ligands which are functionally equivalent. Such medicaments may also include one or more secondary neuroprotective agents.

Neuroprotective effect of growth hormone

Rapid and accurate in-vivo assessment of cerebral white matter injury particularly for pre-term infants, for timely treatment and/or prediction of outcomes has been very limited. This invention exploits the discovery that reduced high-frequency EEG intensity, particularly as shown by the upper spectral edge frequency, is a good indicator of cerebral white matter neural injury and is well correlated with MRI results. With more experience of clinical cases, a set of simple rules such as 'if the spectral edge value is below 8 Hz there is a high likelihood of injury' may be validated, yet the EEG technology involved is largely invisible to the user. In the invention, EEG signals are processed by software to obtain, store, and graphically display bilaterally collected EEG spectral edge and intensity values over from hours to weeks. Rejection of corrupted signals by filtering and gating means is responsive to incoming signal characteristics, to additional inputs such as motion sensors or impedance tests, and to patient data (gestational age in particular). The invention includes the software and methods of use.

Processing EEG signals to predict brain damage

A method for treatment or prophylaxis of a patient suffering from functional symptoms of Parkinson's disease, especially as a consequence of damage to dopaminergic neurons, by administering to the patient a neuroprotective amount of a peptide selected from the tripeptide gly-pro-glu (GPE) and analogs and mimetics thereof, preferably GPE. The GPE will usually be administered subsequent to the onset of Parkinson's disease but prior to the damage of said dopaminergic neurons.

Methods to improve neural outcome

An intelligent brain rescue instrument for identifying, monitoring, and guiding the application of brain therapies to patients with evolving brain injuries, comprises an input for acquiring a multiple number of signals each indicative of a different biochemical or biophysical parameter of a patient, and a computer to continuously sample each of the acquired signals and display to a user on a monitor at least some of the parameters. The displayed parameters are selected by system software embodying expert analytical rules as the most significant parameters, or as parameters having values indicative, or predictive at any time of actual, or potential future deterioration of the brain state of the patient.

Brain rescue instrument and method

The tripeptide glycine-proline-glutamine (GPE) may be administered before, or usually after, injury to reduce damage to the central nervous system. GPE appears useful for neuronal rescue particularly but not exclusively within the hippocampus. Advantages of GPE include: (a) that it crosses the blood-brain barrier, so is effective by injected peripheral administration, (b) it is unlikely to challenge the immune system, (c) it is cheap, and (d) its therapeutic ratio is high. GPE may also be infused into the CSF. It may be administered prior to parturition or elective brain or cardiac surgery. Transdermal routes may be useful for chronic neural disorders. The CNS of mammals (including foetal mammals) after trauma including hypoxic/ischaemic experimental insults showed reduced damage under GPE protection as measured by histological assessment of cell damage or death and regional shrinkage.

Use of GPE to protect glial cells or non-dopaminergic cells from death from neural injury or disease

A method for detecting white matter neural injury and predicting neurological outcome for a patient, comprises acquiring EEG signal(s) from the surface of the head of the patient, and analyzing the frequency distribution or content of the signal(s) to produce output information indicative of cerebral white matter injury for the patient. Loss or reduction of activity in the upper portion or spectral edge of the EEG frequency domain particularly in the immature brain is predictive of neural dysfunction. A system for detecting white matter neural injury and predicting neurological outcome for a patient is also described.

Method and system for detecting white matter neural injury and predicting neurological outcome particularly for preterm infants

An intelligent brain rescue instrument for identifying, monitoring, and guiding the application of brain therapies to patients with evolving brain injuries, includes an input for acquiring a multiple number of signals each indicative of a different biochemical or biophysical parameter of a patient, a computer to continuously sample each of the acquired signals and display to a user on a monitor at least some of the parameters, the displayed parameters being selected by system software embodying expert analytical rules as the most significant parameters, or as parameters having values indicative, or predictive at any time of actual, or potential future deterioration of the brain state of the patient.

This invention relates to the use of the tripeptide Gly-Pro-Glu (GPE) or analogs thereof for the treatment of conditions of the central nervous system (e.g. cerebral vasculitis) in which the amount of the neural enzymes nitric oxide synthetase (NOS) and/or glutamic acid decarboxylase (GAD) is reduced.

Regulation of neural enzymes

Disclosed herein is a method for protecting dopaminergic neurons of a mammal against death resulting from Parkinson's disease. The method comprises administering a neuroprotective amount of the tripeptide Gly-Pro-Glu.

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Auckland, New Zealand

Christopher E Williams