Growth factors and Parkinson's disease -- Where next?

June 04, 2020

Amsterdam, NL, June 4, 2020 - Growth factors such as glial cell line-derived neurotrophic factor (GDNF) were initially thought to be exciting new treatments for Parkinson's disease (PD), but trials have been disappointing. A panel of prominent leaders in the field convened to discuss whether there is a future for this approach and what any future PD trial involving GDNF and other GDNF family neurotrophic factors should consider. Their discussions and recommendations are published in the Journal of Parkinson's Disease.

"There is clear evidence that GDNF and related growth factors can restore the dopaminergic nigrostriatal pathway in several animal models of PD," explained lead author Roger A. Barker, PhD, Cambridge Centre for Brain Repair, Department of Clinical Neuroscience and WT-MRC Cambridge Stem Cell Institute, Cambridge, UK. "However, this has yet to translate into a clinically meaningful and robust response in patients."

Growth factors support the development, growth, and survival of cells in the body and brain. The concept of repairing the brain with growth factors has been pursued for many years in a variety of neurodegenerative diseases including primarily PD. Their properties make them an exciting prospect for developing new treatments that could help repair the damage caused in PD.

An international group of experts met to discuss the history and current status of GDNF and related growth factor neurturin (NRTN) therapy for PD, comprehensively reviewing preclinical and clinical studies. Critical evaluation led to conclusions about what has been achieved and what has not been shown using these agents. It was generally agreed that GDNF and NRTN have worked relatively well in neurotoxic animal models of PD, but that their translation to the clinic has so far failed to show a major impact, perhaps highlighting the predictive limitations of toxin animal models being commonly used in the preclinical space in PD to look at disease modifying therapies.

"As to what any trial should look like, there is still much debate as to what primary end-point should be used and at what time point, and input from the patient community on this will be vital going forward," noted co-author Anders Bjorklund, MD, PhD, Wallenberg Neuroscience Center, Lund University, Lund, Sweden.

The workshop participants agreed that the question of whether GDNF has a competitive future in the treatment of PD is still unclear. They offered recommendations about what future trials with GDNF should consider and how they might be designed. For example, compared to the relative complexity of the neurosurgery needed to implant an infusion delivery system and ongoing infusions used in a recent GDNF trial, they felt a viral delivery system using newer modified approaches requiring less complex surgery would be more advantageous. In addition, they indicated that early stage PD patients would most likely benefit from such treatment because this group would have the most neurons and fibers left to rescue, with evidence of fiber loss restricted to the dorsal striatum, where the therapeutic agent could be targeted.

The workshop concluded that future trials with GDNF and related agents should be considered but that much more careful attention is needed to be given to all aspects, including the type of patient enrolled; the form of growth factor given; the dose and volume of agent given; the mode of delivery and length of follow-up along with optimal assessment tools.
-end-
Co-author Anthony E. Lang, MD, The Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, and the Department of Medicine, University of Toronto, Toronto, ON, Canada, added, "We have recommended that future trials with this or related agents should be considered, but that much thought needs to be given to all aspects of any such trial."

"This meeting uniquely brought together all those who have worked on GDNF and related factors over the last 25 or so years," concluded Patrik Brundin, MD, PhD, Center for Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI, USA, a workshop participant and co-Editor-in-Chief of the journal. "It led to an informed, honest, and stimulating discussion about the future of this field, in a way that has to be seen as an exemplar of how best to take forward any such experimental therapies for this condition."

IOS Press

Related Brain Articles from Brightsurf:

Glioblastoma nanomedicine crosses into brain in mice, eradicates recurring brain cancer
A new synthetic protein nanoparticle capable of slipping past the nearly impermeable blood-brain barrier in mice could deliver cancer-killing drugs directly to malignant brain tumors, new research from the University of Michigan shows.

Children with asymptomatic brain bleeds as newborns show normal brain development at age 2
A study by UNC researchers finds that neurodevelopmental scores and gray matter volumes at age two years did not differ between children who had MRI-confirmed asymptomatic subdural hemorrhages when they were neonates, compared to children with no history of subdural hemorrhage.

New model of human brain 'conversations' could inform research on brain disease, cognition
A team of Indiana University neuroscientists has built a new model of human brain networks that sheds light on how the brain functions.

Human brain size gene triggers bigger brain in monkeys
Dresden and Japanese researchers show that a human-specific gene causes a larger neocortex in the common marmoset, a non-human primate.

Unique insight into development of the human brain: Model of the early embryonic brain
Stem cell researchers from the University of Copenhagen have designed a model of an early embryonic brain.

An optical brain-to-brain interface supports information exchange for locomotion control
Chinese researchers established an optical BtBI that supports rapid information transmission for precise locomotion control, thus providing a proof-of-principle demonstration of fast BtBI for real-time behavioral control.

Transplanting human nerve cells into a mouse brain reveals how they wire into brain circuits
A team of researchers led by Pierre Vanderhaeghen and Vincent Bonin (VIB-KU Leuven, Université libre de Bruxelles and NERF) showed how human nerve cells can develop at their own pace, and form highly precise connections with the surrounding mouse brain cells.

Brain scans reveal how the human brain compensates when one hemisphere is removed
Researchers studying six adults who had one of their brain hemispheres removed during childhood to reduce epileptic seizures found that the remaining half of the brain formed unusually strong connections between different functional brain networks, which potentially help the body to function as if the brain were intact.

Alcohol byproduct contributes to brain chemistry changes in specific brain regions
Study of mouse models provides clear implications for new targets to treat alcohol use disorder and fetal alcohol syndrome.

Scientists predict the areas of the brain to stimulate transitions between different brain states
Using a computer model of the brain, Gustavo Deco, director of the Center for Brain and Cognition, and Josephine Cruzat, a member of his team, together with a group of international collaborators, have developed an innovative method published in Proceedings of the National Academy of Sciences on Sept.

Read More: Brain News and Brain Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.