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Gene therapy with GDNF: the results of the US trial

Original article: Trial of magnetic resonance-guided putaminal gene therapy for advanced Parkinson’s disease. Mov Disord: May 30, 2019

The takeaway

A phase I open label, escalating dose trial of enhancing GDNF through gene therapy has shown this method is safe and well tolerated in a small study of 13 people with Parkinson’s.

Why is it important?

This study has shown both safety and tolerability, and has identified ways in which future GDNF trials can be improved to properly put GDNF to the test.



  • Novelty 80% 80%
  • Proximity 70% 70%
  • Deliverability 70% 70%

Impact Opinion

“Following the disappointing results of the Bristol GDNF trial, it is reassuring to see that GDNF has not been completely abandoned. This new clinical trial suggests that GDNF gene therapy is both safe and well tolerated, and it hints at some encouraging additional benefits (eg. the brain imaging data and no change in medication).

Obviously a large, longer Phase II clinical trial is necessary to determine if the treatment has any efficacy, and the planning of that project is now well underway.”


GDNF, or Glial derived neurotrophic factor, is a substance made by non-neuronal cells in the brain to support and promote the growth of neurons. Several trials have tried to test its potential to slow, stop or reverse Parkinson’s through its effects on dopamine neurons, using different ways of delivering it into the brain.

The recent GDNF trial run in Bristol, UK, used a novel device which, through convection enhanced delivery, infused GDNF directly into the movement centre of the brain. Although participants in this trial did not show improvements in their movement suggesting disease modification, scans assessing dopamine neuron function indicated some effects had been achieved. Previous trials with GDNF, including one of its homologue Nurturin, delivered through gene therapy were also unsuccessful.

This trial run in Bethesda, US, sought to build on the Nurturin trial by delivering GDNF gene therapy using MRI of the putamen (one of the main movement centres affected in Parkinson’s) to monitor how effectively this region was being covered during surgery using a specific tracer, gadoteridol. The design also looked at the effects of increasing amounts of infusion.

The details

Thirteen people with Parkinson’s received the gene therapy infusion, with six people receiving a lower dose, six receiving the intermediate dose and one receiving the highest dose. They had routine neurological assessments of their movement with the UPDRS, and had FDOPA scans at baseline, that is before the surgery, and then again at 6 and 18 months follow up to assess dopamine neuron function.

The procedures and gene therapy were well tolerated and safe. No UPDRS changes were seen for the group as a whole, or any changes in the amount of medications needed for symptom control, although the researchers point out that while this was true for most participants, 2 individuals did in fact reduce the amount of medication they were taking. The MRI scans assessing how much of the putamen had been covered by the infusion indicated this was a quarter of it (26% on average). However, the FDOPA scans did show improvements in dopamine neuron function compared to baseline at both 6 and 18 months post-operatively.

Next steps

A future trial is already planned to attempt to achieve greater coverage of the putamen through infusing a larger volume but also through a different surgical approach.

These are important next steps required to optimize this method of gene therapy before a proper test of its effect can be properly assessed. 

Original article: Heiss, JD, Lungu, C, Hammoud DA, Herscovitch P, Ehrlich, DJ, Argersinger D P, Bankiewicz KS. May 30, 2019. Trial of magnetic resonance-guided putaminal gene therapy for advanced Parkinson’s disease.


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