A lay summary written by Isabela Ramnarine & reviewed by Dr Scott Allen.
Glial cell-line derived neurotrophic factor (GDNF) is a naturally occurring protein found in the brain. In animal models, the delivery of GDNF to appropriate areas has been shown to help damaged and dying brain cells seen in people with Parkinson’s disease to recover and regrow. Current treatments for Parkinson’s disease only help to improve symptoms, they do not stop the disease from progressing.
This study, led by Professor Gill was ground-breaking research which used many new concepts in humans in order to investigate if the direct injection of GDNF into a deep part of the brain that needs it most (the Putamen) is able to “undo” the brain damage seen in patients with Parkinson’s.
In total, forty-one patients underwent robot assisted surgery where four tubes were inserted into the brain and a port was attached to the side of their head in order for medication to be given. To allow for comparison, participants were randomly split so that half were given the GDNF drug every month for nine months and the other half were given a placebo (inactive “dummy” drug). The trial was double blinded meaning neither the patient nor doctors knew who was getting what. After nine months, all participants were offered the actual drug. This ensured patients did not have to go through brain surgery without being offered any potential beneficial treatments, which would have been unethical.
At the start of the study, all participants had brain scans to see how well the brain cells that produce dopamine, the chemical that is low in people with Parkinson’s, were working. Success of the study was determined by the improvement in patients’ Unified Parkinson’s Disease Rating Scale (UPDRS) motor score. This is a reliable scoring system frequently used in clinical practice and research as a way of assessing movement and other daily living complications experienced by patients with Parkinson’s disease.
Disappointingly, the results of the study showed although an improvement in the UPDRS score was in patients receiving GDNF, the difference between the two groups was not big enough for valid conclusions about its effectiveness to be made. Repeat brain scans at the end of the study showed encouraging results of the drug being uptaken in the required areas. This is a promising initial finding which may indicate the start of these brain cells being reactivated. Patients did not complain or report serious side effects from taking the drug.
Future research is needed to build upon the successful methods of targeted drug delivery identified in this study. It was suggested that GDNF may work better if it is given to patients at an earlier stage of the disease as well as an increased dose and duration of administering the medication. When given earlier in a disease course, more connections in the brain should be intact with less damage that needs to be corrected. Ideally, by being able to slow down, stop or reverse the progression of brain changes seen in Parkinson’s disease, the symptoms experienced by patients will be reduced, thus, hopefully improving their quality of life.
Randomized trial of intermittent intraputamenal glial cell line-derived neurotrophic factor in Parkinson’s disease.
Alan Whone et al Brain, Volume 142, Issue 3, March 2019, Pages 512–525
References
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Grondin R, Zhang Z, Yi A, Cass WA, Maswood N, Andersen AH, et al. Chronic, controlled GDNF infusion promotes structural and functional recovery in advanced parkinsonian monkeys. Brain 2002; 125 (Pt 10): 2191–201.
Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F. GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 1993; 260: 1130–2.
Whone, A., Luz, M., Boca, M., Woolley, M., Mooney, L., Dharia, S., Broadfoot, J., Cronin, D., Schroers, C., Barua, N.U. and Longpre, L., 2019. Randomized trial of intermittent intraputamenal glial cell line-derived neurotrophic factor in Parkinson’s disease. Brain, 142(3), pp.512-525.