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 neurodegenerative conditions such as Parkinson’s, exhibiting powerful neuroprotective properties.

Testing Novel Approaches to Target Neurotrophic Factors for Parkinson’s

Cure Parkinson’s trustees have approved the funding of a new study focused on an interesting neurotrophic factor called cerebral dopamine neurotrophic factor or CDNF.

Professor Mart Saarma and colleagues at the University of Helsinki have discovered a tiny fragment of the CDNF protein, which they have called 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 normal CDNF. They will now test 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.

The delivery of neurotrophic factors to the brain is challenging as they cannot cross the blood-brain barrier. Currently getting growth factors into the brain involves invasive methods like brain surgery. We hope that this new study being conducted by Prof Mart Saarma’s lab will allow for the development of a less invasive neurotrophic approach. 

Dr Simon Stott, Deputy Director of Research – Cure Parkinson’s

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

In February 2019, the results of the Phase II 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.

Delivery of neurotrophic factors in 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 minimally invasive for patients and therefore could make growth factors a viable restorative therapy for Parkinson’s.

Nanoform Finland Plc. and Herantis Pharma Plc. announced their collaboration to seek to enhance nasal drug delivery to the brain of Herantis’ CDNF and xCDNF therapies using Nanoform’s biological nanoparticle technology.

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 drugs to the brain and has ensured that the growth factors are only delivered to the area where nerve 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 until this condition is cured!

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