Nerve growth or neurotrophic factors are small proteins that support neurons and encourage their growth and survival during development. There has been considerable preclinical research exploring their potential use in Parkinson’s.

They have been shown to rescue neurons in laboratory models of Parkinson’s, exhibiting powerful protective properties.

Testing Novel Approaches to Target Neurotrophic Factors for Parkinson’s

Cure Parkinson’s is funding two studies of interesting neurotrophic factors: called cerebral dopamine neurotrophic factor or CDNF and GDF5.

Professor Mart Saarma and colleagues at the University of Helsinki have discovered a tiny fragment of the CDNF protein (C-CDNF) that can pass through the blood brain barrier (the protective membrane surrounding the brain and central nervous system) and still exhibit the positive properties of the larger molecule, CDNF. They are testing this protein in laboratory models of Parkinson’s to assess its potential as a neuroprotective therapy. It is hoped that C-CDNF will allow for a more straightforward oral or peripheral administration of a future neurotrophic factor based therapy for Parkinson’s.

Professors Gerard O’Keeffe and Aideen Sullivan in Cork, Ireland have determined that the nerve growth factor GDF5 provides brain protective benefits in models of Parkinson’s. The team will be comparing and combining two nerve growth factors (GDNF and GDF5) and will use modified viruses to carry the growth factors directly into the brain of Parkinson’s models in the lab. If successful, this project will lay the foundations for GDF5 to move forward into clinical trials.

Neurotrophic factors – the background

The translation of neurotrophic factor research into humans has not been easy.

In February 2019, the results of the phase 2 Bristol study investigating the use of a neurotrophic factor called glial cell-derived neurotrophic factor (or GDNF) in people with Parkinson’s were published. While there were some encouraging signs of improvements in those receiving GDNF, there was no significant difference between the active treatment group and those who received placebo on any assessments of Parkinson’s symptoms in the nine month trial.

Progress in the field of neurotrophic factors

Gene therapy:

December 2020: Brain Neurotherapy Bio, Inc. (BNB), a private clinical-stage gene therapy development company, has reached an agreement to merge and become a wholly-owned subsidiary of Asklepios BioPharmaceutical, Inc. The union of BNB and AskBio will provide critical financial support and access to adeno-associated virus (AAV) gene therapy for Parkinson’s.

Delivery of neurotrophic factors into the brain

Work is intensifying in the delivery of small fragment growth factors to the brain, such as the Cure Parkinson’s funded study of C-CDNF.  If effective pre-clinically, these small fragments may be developed for subcutaneous or nasal delivery which would be less invasive and therefore could make growth factors a viable restorative therapy for people with Parkinson’s.

Infusion:

In the recent trials in Bristol of GDNF and in Scandinavia with CDNF, a novel convection enhanced delivery device developed by Renishaw has been used.  This has enabled pin-point precise delivery of the molecules to the brain and has ensured that the neurotrophic factors are only delivered to the area where brain cells have been affected. The device has not received regulatory approval so can only be used in a clinical trial setting.  However Herantis Pharma has opted to explore alternative delivery approaches for CDNF that would not involve invasive brain surgery for infusions of growth factors.

Nanoformulation:

A recent paper from Dr Olesja Bondarenko and Professor Mart Saarma, published in Frontiers of Cellular Neuroscience, reviews the array of different neurotrophic factor delivery methods for Parkinson’s based on the clinical trials of GDNF and CDNF to date, as well as the current and future possibilities of using nano-sized particles as carriers of these drugs into the brain.

Nanoformulation is an exciting strategy to deliver drugs into the brain. It is a non-invasive delivery method that involves the incorporation of drugs into small carriers that can be specifically targeted to areas where they can have the most therapeutic effect. Such methods may be critical to optimise the effectiveness of future Parkinson’s treatments

Dr Leah Mursaleen, Research Manager, Cure Parkinson’s

Cure Parkinson’s continues to explore every opportunity for neurotrophic factors in Parkinson’s and will persevere within this field of research.

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