Parkinson’s and nerve growth factors

In the Bristol trial of GDNF and in Scandinavia with another neurotrophic factor called CDNF, a ‘convection enhanced delivery device’ developed by Renishaw was used to enable pin-point precise delivery of the growth factor molecules directly into the brain ensuring that the nerve growth factor was delivered to the area where brain cells have been affected by Parkinson’s. This method of delivery in invasive and involved extensive brain surgery.

Work is intensifying in the delivery methods of small fragment nerve growth factors to the brain, such as the Cure Parkinson’s funded study of C-CDNF.  If effective in the laboratory, these smaller fragments of growth factor may be developed for simple skin injection or nasal delivery which would be less invasive and therefore could make growth factors a viable restorative therapy for people with Parkinson’s. Cure Parkinson’s eagerly awaits the results of this promising research project.

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The Finland-based company Herantis Pharma completed their Phase 1a clinical trial of ‘HER-096’ in late 2023. HER-096 is another small molecule version of the growth factor CDNF, having the potential to pass through the blood-brain-barrier, eliminating the need for invasive surgery.

In the topline results, the company announced that the trial met its primary and secondary outcomes, indicating the treatment was safe and tolerable when taken by healthy volunteers as well as showing evidence of reaching the brain. The company hope HER-096 will be tested in people with Parkinson’s and look to continue the clinical development of this molecule.

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There is an urgent need for treatments to slow or stop the progression of Parkinson’s and the use of gene therapy via gene replacement offers the potential to achieve this with a single treatment. The development of conventional treatments for Parkinson’s in reaching the brain is made particularly difficult because of the semi-permeable nature of the protection of the blood-brain-barrier which protects the brain from harmful compounds circulating in the bloodstream.

Viral vectors (or carriers) have shown potential in certain neurodegenerative gene therapy treatments. Researchers are using carefully engineered safe viruses to act as biological delivery vessels to carry their modified gene contents to the requisite part of the brain – in this case the gene needed in the brain to make the nerve growth factor is placed inside the virus shell which then ‘infects’ the area of the brain with its contents. The delivered gene therapy then provides instructions for the surrounding brain cells to start naturally producing growth factor on their own, without further treatment.

The other benefit is that this exciting and pioneering delivery approach removes the need for highly invasive surgical infusion treatment.

Earlier this year, the US biotech company AskBio announced their phase 1 clinical trial of ‘AB-1005’ had met its primary outcome. AskBio has developed AB-1005 to modify the progression of Parkinson’s by introducing a gene that stimulates cells to produce the growth factor GDNF. The gene is introduced to the brain cells affected by Parkinson’s with a one-time surgical delivery.

Eleven people with Parkinson’s participated in this 18-month clinical trial and researchers found that AB-1005 was safe and well tolerated by the participants. AskBio have only released the preliminary results for the trial at this stage; however, a phase 2 trial is currently being set up and patient screening is anticipated to begin in the first half of 2024.

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Nanoformulation:

A recent paper from Dr Olesja Bondarenko and Professor Mart Saarma, published in Frontiers of Cellular Neuroscience, reviews the array of different nerve growth 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.

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