Introduction

Dr Jian Guan completed her Bachelor of Medicine in China in 1982. After eight years of practice as a Paediatrician she obtained a PhD. in Paediatrics at the University of Auckland in 1996. Throughout her career, she has pioneered research in insulin-like growth factor-1 (IGF-1) and its role in brain function and metabolism.

Dr Jian Guan serves as the Chief Scientist at The cGP Lab. She is also an Honorary Associate Professor in the Department of Pharmacology and Clinical Pharmacology at the Faculty of Medical and Health Sciences, University of Auckland, New Zealand's highest ranking university.

With an esteemed career spanning numerous collaborations—including with Professor Sir Peter Gluckman, former Principal Science Adviser to the Prime Minister—Jian has published 80 research papers, 34 of which have been cited over 34 times.

Her academic research career primarily focused on the pharmaceutical and nutraceutical development of IGF-1-derived small peptides for treating neurodevelopmental, cerebral vascular and metabolic diseases.

A recent breakthrough in identifying natural cGP in food sources resulted in the development of a standardised cGP food ingredient called cGP-PRo® for human health applications.

Research

An internationally recognised scientist, Dr Guan continues to lead her research field.

Dr. Guan’s research is distinguished by her discovery of the protective effects of IGF-1 and its metabolites, cGP and a related molecule called GPE in acute brain injury, chronic neurological conditions and metabolic conditions such as diabetes.

Over the past 20 years, she has collaborated with academics worldwide. In New Zealand, she has worked with institutions such as the University of Otago, the University of Canterbury, and Auckland University of Technology on a wide range of topics, including brain aging, cognitive impairment, and the development of biomarkers for Parkinson’s disease. Additionally, she partnered with the National Institute for Stroke & Applied Neurosciences (Auckland University of Technology) to investigate biomarkers for long-term stroke recovery and brain injury prognosis.

Internationally, Dr. Guan's cGP-related research spans collaborations with leading academics from Sweden, the United States, Spain, China, and Russia.

Her specific research topics on cGP include:

  • The role of cGP in improving brain development.

  • Biological interactions of cGP and binding proteins (IGFBPs).

  • The effects of cGP on recovery from peripheral neuropathy.

  • The mechanism of cGP on regulating IGF-1 function.

  • Effects of cGP in cancer.

  • Association of cGP with cognitive function in the elderly.

  • The role of cGP in stroke recovery in humans.

  • The role of cGP in pregnancy-associated hypertension and obesity.

  • Mechanism of cerebral radiation-induced brain injury.

  • The effect of cGP on mood (depression and anxiety)

  • The effect of cGP in Rett syndrome.

  • The function of cGP in vascular remodelling (rebuilding the microcirculation)

  • The role for IGF-1 in vascular degeneration of PD brains.

The role of cGP in vascular complications of diabetes

Type-2 diabetes is often accompanied by vascular complications that significantly impact a person’s health and quality of life. These complications arise from impaired blood flow and damage to small blood vessels, affecting various organs and bodily functions.

The most common and debilitating of these conditions is peripheral neuropathy, which results in nerve damage, leading to loss of sensation, pain, and weakness in the limbs. It is also the leading cause of non-traumatic amputations, with no effective treatment currently available.

Other serious vascular complications include diabetic nephropathy and diabetic retinopathy. Diabetic nephropathy occurs when prolonged high blood sugar damages the kidneys, reducing their ability to filter waste effectively and often leading to kidney failure. Diabetic retinopathy, on the other hand, affects the small blood vessels in the eyes, potentially causing vision loss and, in severe cases, blindness.

Dr Guan's research has shown that individuals with metabolic syndrome, particularly those with high blood pressure, tend to have lower levels of cGP in their bloodstream.

Given cGP’s role in regulating blood vessel function, Dr Guan hypothesised that cGP deficiency may contribute to the progression of these vascular complications. To address this, an open-label trial was conducted to evaluate the potential benefits of natural, food-based cGP-PRo® supplementation.

The study looked at whether cGP-PRo® can improve blood flow to the limbs and enhance sensory function in individuals with diabetic peripheral neuropathy, offering a potential new approach to managing this challenging condition.

Timeline

1990 - 1995
Dr. Jian’s research journey began by understanding IGF-1 and its role in neuroprotection and neurorepair. During her quest to uncover the brain-made mechanisms to reduce damage after suffering a brain injury, she discovered GPE (Glycine-Proline-Glutamate).

GPE is a metabolite that is yielded by the enzymatic breakdown of IGF-1 and further research into GPE suggested that it has neuroprotective benefits that helped in recovery from stroke. Thus, highlighting its therapeutic potential.

1995 - 2000
With the aim of focusing on GPE rather than IGF-1 as a much simpler model for protection against brain injury, NeuroNZ, the first university-based pharma company was formed to translate these findings into commercial research. NeuroNZ was later privatised to become Neuren Pharmaceuticals, a company that is now developing therapies for highly debilitating neurodevelopmental disorders that emerge in early childhood.

2000 - 2005
During her time at Neuren, Jian studied the effects of GPE on recovery from stroke. A deeper investigation into GPE suggested that it is unstable and therefore its structural analogue was used for the development of a drug by the company (now known as Daybue and recently been approved by FDA as a treatment for Rett Syndrome).

Continued research into IGF-1 metabolites led to the discovery of cGP (cyclic-glycine-proline), a small yet stable compound responsible for maintaining cognitive health. Jian conducted extensive studies in understanding this molecule, its mode of action and pharmacological profile.

She then conducted studies for the preclinical development of a cGP analogue on treating cognitive impairment (NNZ2591 - currently under trial by Neuren Pharmaceuticals).

2005 - 2010
Jian left her role at Neuren Pharmaceuticals to continue her work as an academic researcher. She focused on understanding the mechanism of cGP in normalising IGF-1 function and then studied broader clinical applications of cGP in age-related conditions affected by IGF-1 such as Parkinson’s disease, Alzheimer’s disease and Dementia.  Concurrently, she conducted nutritional interventional studies to improve mental well-being in aged and developing brains and was involved in the development of an infant formula.

2010 - 2015
Jian continued her research of cGP in lactating mothers and spent time understanding the role of complex dairy lipids in brain development. Studies in animal models suggest the importance of cGP during early postnatal development.

2015 - 2020
Early in 2015, Jian discovered cGP in natural foods – NZ blackcurrants. A clinical trial using natural cGP supplement in Parkinson’s Disease patients suggested its bioavailability and efficacy in improving mood (anxiety/depression)

Later, using this information and with the aim of creating a range of nutraceuticals that deliver natural cGP- The cGP Lab Limited was founded.

2020 - 2025
cGP-PRo is the first ingredient of its kind that aims to deliver a standardised, daily dose of cGP to protect brain health and cognitive function.

1990 - 1995

1995 - 2000

2000 - 2005

2005 - 2010

2010 - 2015

2015 - 2020

2020 - 2025

Consultancy & Collaborations

For over 20 years, in her role as a scientific consultant for Auckland UniServices Ltd (a division of the University of Auckland), Dr. Guan has provided scientific expertise and technical support to organisations in New Zealand and internationally.

Her work includes leading research projects in collaboration with Fonterra New Zealand, Neuren Pharmaceuticals (formerly NeuronZ Ltd), Living Cell Technologies, and Pacific Brands, as well as offering consultancy services for Plant & Food Research NZ and Deer Velvet NZ.

Her research has been primarily funded by the Ministry of Business, Innovation and Employment, supporting commercial development initiatives within the Primary Growth Partnership (PGP), with a total funding allocation of $12 million.

A Selection of Dr Guan’s Granted Patents Prior to Joining The cGP Lab

  1. “Regulation of neural enzymes”.

    1. US6365573 B1 APR 2, 2002

    2. WO1998014202 A1

    3. AU4639197

    4. EP0929313 A4

    5. CA2267523 A1

    Abstract:
    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.
    ‍
    Inventor:
    ‍    Peter D Gluckman
    Christopher E. Williams
    Jian Guan
    ‍
    Assignee:
    ENDOCRINZ Ltd
    Neuren Pharmaceuticals Ltd

  2. “Regulation of tyrosine hydroxylase”.

    1. US6617311 B1 SEP 9, 2003

    2. WO1999065509 A1

    3. EP1087782 A4

    4. CN1305383 A

    5. CA2334528 A1

    Abstract:
    This invention relates to methods of regulating the effect of tyrosine hydroxylase (TH). In particular it relates to increasing the effective amount of TH in the central nervous systems (CNS) for the purpose of increasing TH-mediated dopamine production in the treatment of conditions such as Parkinson's disease.
    ‍
    Inventor:
    ‍    Peter D Gluckman
    Christopher E. Williams
    Jian Guan
    ‍
    Assignee:
    ENDOCRINZ Ltd
    Neuren Pharmaceuticals Ltd

  3. “Regulation of tyrosine hydroxylase by GPE”.

    1. US6933282 B2  AUG 23, 2005

    Abstract:
    Embodiments of this invention include methods for increasing the amount of the enzyme tyrosine hydroxylase (TH) in the central nervous system (CNS) of mammals in need of an increase in TH. Methods include the use of the tripeptide, gly-pro-glu (GPE) to increase TH in the CNS. GPE can increase the amount of TH and/or decrease the loss of TH in conditions characterized by a loss of dopamine, such as Parkinson's disease and CNS injury. GPE may act to increase the expression of TH or by inhibiting a decrease in TH expression within the CNS or by inhibiting the loss of TH-containing neurons within the CNS. By increasing the amounts of TH in the CNS, GPE can increase the amount of the neurotransmitter, dopamine, in areas of the CNS responsible for adverse symptoms of neural injury or disease.
    ‍
    Inventor:
    ‍    Peter D. Gluckman
    Jian Guan
    Tajrena Alexi
    ‍
    Assignee:
    ENDOCRINZ Ltd
    Neuren Pharmaceuticals Ltd

  4. “Methods to improve neural outcome”.

    1. US6187906 FEB 13, 2001

    Abstract:
    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.
    ‍
    Inventor:
    ‍    Peter D. Gluckman
    Christopher E. Williams
    Jian Guan
    ‍
    Assignee:
    ENDOCRINZ Ltd
    Neuren Pharmaceuticals Ltd

  5. “Effects of Glycyl-2 Methyl Prolyl-L-Glutamate on Neurodegeneration".

    1. US7605177 B2 OCT 20, 2009

    Abstract:
    This invention provides analogs and peptidomimetics of glycyl-L-prolyl-L-glutamic acid (GPE). In particular, this invention relates to GPE analogs and peptidomimetics that are anti-apoptotic, anti-necrotic and have neuroprotective effects. These agents are useful in treating neurodegeneration and behavioural disorders caused by toxins, traumatic brain injury and autoimmune disorders of the brain, such as multiple sclerosis and in reducing seizures.
    ‍
    Inventor:
    Peter David Gluckman
    Gregory Brian Thomas
    Jian Guan
    Michael Dragunow
    Ashmit Kumar Anand
    Frank Sieg
    Margaret Anne Brimble
    ‍
    Assignee:
    Neuren Pharmaceuticals Ltd

  6. “Cyclic G-2-Allyl-Proline in treatment of Parkinson’s Disease”.

    1. US7776876 B2  AUG 17, 2010

    Abstract:
    Embodiments of this invention provide methods for therapeutic use of cyclic G-2-Allyl Proline to treat disorders of dopaminergic neurons, including Parkinson's disease. Cyclic G-2Allyl P is neuroprotective and has utility as a therapeutic agent for treatment of diseases and other conditions characterised by degeneration and/or death of dopaminergic neurons and the adverse symptoms of such degeneration and/or death. Such symptoms include loss of cognition and motor function. Compounds are also useful for manufacture of medicaments including tablets, capsules and injectable solutions that are useful for treatment of such conditions.
    ‍
    Inventor:
    Margaret Anne Brimble
    Jian Guan
    ‍
    Assignee:
    Neuren Pharmaceuticals Ltd

  7. “Neuroprotective bicyclic compounds and methods for their use”.

    1. US8067425 B2  NOV 29, 2011

    2. WO2005023815 A3

    3. EP1664050 A2

    Abstract:
    Embodiments of this invention provide novel cyclic compounds structurally related to diketopiperazines and methods for their therapeutic use. Such compounds are neuroprotective and have utility as therapeutic agents for treatment of diseases, injuries and other conditions characterized by neuronal degeneration and/or death. Compounds are also useful for manufacture of medicaments useful for treatment of such conditions.
    ‍
    Inventor:
    Margaret Anne Brimble
    Jian Guan
    Frank Sieg
    ‍
    Assignee:
    Neuren Pharmaceuticals Ltd

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