Biomaterials in cell replacement therapies for Parkinson’s

Using biological materials to create scaffolds that shield and support cells transplanted into the brain to replace those lost to Parkinson’s could promote their survival and growth.

Despite resources, efforts and hope invested in clinical trials of cell replacement therapies for Parkinson’s, these have not yet delivered on their promise. This review highlights an important next step in refining existing methods that could improve outcomes in upcoming trials.

Since the first study to investigate the potential of transplanting embryonic dopaminergic neurons into the brain of experimental animals in the 1970s, cell replacement therapies have come a long way. The theory behind this ambitious approach is that it should be possible to replace dopaminergic neurons lost to Parkinson’s with young ones derived from donated tissue. When transplanted into the areas which are critical for movement and where dopamine is needed, these neurons should grow and function in a way that restores function and enables recovery.

Early open label studies reported improvements in terms of movement and quality of life. However, the two randomized placebo controlled clinical trials in people with Parkinson’s which took place in the early 2000s failed to achieve their primary end point, that is, consistent improvements on the UPDRS motor assessment. In addition, a subset of patients developed graft induced dyskinesias. Although the reasons for these worrying adverse effects and lack of clinical benefit are unknown, patient selection, tissue preparation, as well as the use of immunosuppression (to prevent rejection of the transplanted tissue) were clearly important determinants of overall outcome. We do know that those who benefited the most had less severe symptoms and responded better to levodopa.

We also know that transplanted neurons fail to thrive mostly due to environmental causes. How can their survival and growth be ensured? This is a major issue that limits clinical benefit

Biomaterials, in particular injectable hydrogels mostly consisting of naturally occurring substances like collagen, and may include a synthetic component, are being studied intensively. These substances have the potential to offer growing neurons structural support, but also by encasing them offer protection from a hostile immune system. This would mean that there is less need for patients to receive immunosuppressant therapy, which may have been linked to reduced clinical benefit seen in the earlier clinical trials. In addition, as neurons require further neurochemical support to grow, trophic factors such as GDNF can be loaded into these biomaterial scaffolds, in the form of long release microbeads for example. The region into which these neurons are transplanted is relatively depleted, and delivering GDNF incorporated into the scaffold has been shown to improve their survival and maturation.

In sum, biomaterials which are safe, non-toxic, structurally stable over long time periods, modifiable chemically and able to carry therapeutic factors may offer an attractive strategy for cell transplantation.

More research and replication of these early promising findings is necessary. Choosing and refining the most suitable biomaterial will also be important if this strategy is to be part of a future clinical trial.

• https://www.cureparkinsons.org.uk/regenerative-medicine-transeuro
• https://www.parkinsonsmovement.com/stem-cell-research/
• https://www.parkinsonsmovement.com/reprogrammed-stem-cell-trial/