In a new series of studies that culminated with an open-label trial , scientists have begun testing the effectiveness of a new treatment — and method of delivery — for Parkinson's disease.
A large team of researchers from various institutions across the United Kingdom and Canada, including the University of Bristol and Cardiff University in the U.K., and the University of British Columbia in Vancouver, Canada, devised and conducted the trial.
In the study, the researchers aimed to restore degrading dopamine-producing brain cells in people who doctors had diagnosed with Parkinson's disease.
Since dopamine is a neurotransmitter that helps regulate the control and agility of body movements, the impaired production of dopamine — due to changes in the brain cells that release it — leads to the motor symptoms that characterize Parkinson's disease.
The research team conducting the current trial decided to try and rehabilitate those brain cells by upping the levels of glial cell line-derived neurotrophic factor (GDNF), a type of protein that supports neuronal health.
In the study paper reporting the results — which appears in the Journal of Parkinson's Disease — the scientists explain that not only did they test a novel therapy but also an innovative administration method — through a port they implanted in the skull.
Initially, the research team conducted a small pilot study with six participants — all living with Parkinson's disease — their main goal being to establish whether or not the new therapeutic approach was safe.
The next stage saw 35 more participants with Parkinson's disease take part in a double-blind trial when neither they nor the researchers administering the therapy knew whether each was dealing with the experimental treatment or a placebo.
This trial lasted for 9 months (40 weeks), during which the team gave half the volunteers monthly infusions of GDNF and administered a placebo to the other half who acted as the control cohort.
Finally, the researchers organized an open-label trial, building on the results of the previous tests. In this trial, volunteers who had previously received GDNF continued to have this treatment for another 40 weeks.
At the same time, those who previously received a placebo now had GDNF for 40 weeks. "From October 2013 through to April 2016, all 41 patients completing the parent study were screened for participation in the extension trial," the researchers write.
To receive the drug, the participants agreed to have a special port implanted into their skills, which allowed the drug infusions to reach their brains directly. Following implantation, the volunteers received, on the whole, over 1,000 drug infusions once every 4 weeks.
When they analyzed the results of the first 9-month (40-week) trial, the researchers saw no changes in the brains of participants who had received a placebo. However, they noted that volunteers who had received the GDNF treatment had a 100 percent improvement in the putamen, the brain region which contains dopamine-producing cells.
"The spatial and relative magnitude of the improvement in the brain scans is beyond anything seen previously in trials of surgically delivered growth-factor treatments for Parkinson's," points out the study's principal investigator Alan Whone.
"This represents some of the most compelling evidence yet that we may have a means to possibly reawaken and restore the dopamine brain cells that are gradually destroyed in Parkinson's," Whone goes on to argue.
At the 18-month mark, when participants had been on the GDNF treatment for either 9 months or the full 18 months, the researchers found that everyone had begun experiencing moderate to significant improvements of their motor symptoms when they compared them with their performance scores before the trials. The researchers also concluded that prolonged exposure to GDNF was safe.
However, the team warns that at the end of the open-label trial, there were no significant differences in terms of symptom improvement between the participants who had received GDNF for 40 weeks (9 months) and those who had received it for double that period.
For this reason, the researchers argue that they need to do further studies, which will assess how long a person should receive the treatment in order to reap the most benefits.
Nevertheless, Steven Gill, study co-author, and designer of the innovative drug-administration device stresses that the current findings suggest that this new therapy is absolutely safe and feasible, and people can administer it for a long time.
Moreover, he notes that administering drugs directly into brain areas they target has the potential to revolutionize therapeutic approaches to neurological conditions.
"This trial has shown that we can safely and repeatedly infuse drugs directly into patients' brains over months or years," Gill says.
目前正在进行这项试验的研究小组决定通过提高神经胶质细胞源性神经营养因子（ GDNF ）的水平来恢复这些脑细胞， GDNF 是一种支持神经元健康的蛋白质。
这项试验持续了9个月（40周），在此期间，研究小组给志愿者每月注射一半 GDNF ，并给另一半作为对照组的志愿者服用安慰剂。
最后，研究人员根据先前试验的结果组织了一项开放标签试验。在这项试验中，先前接受 GDNF 治疗的志愿者继续接受这种治疗40周。
同时，那些以前接受安慰剂的人现在有 GDNF 40周了。研究人员写道：“从2013年10月到2016年4月，完成父母研究的所有41名患者都经过了筛查，以参与延长期试验。”
当他们分析了第一个9个月（40周）试验的结果时，研究人员发现接受安慰剂的受试者的大脑没有变化。然而，他们注意到接受 GDNF 治疗的志愿者在含有多巴胺产生细胞的大脑区域普那门有100%的改善。
研究人员发现，在18个月的时间里，当参与者接受 GDNF 治疗9个月或整整18个月时，他们发现，当他们将运动症状与试验前的表现评分进行比较时，每个人都已经开始经历中度到显著的改善。研究人员还得出结论，长期接触 GDNF 是安全的。
然而，研究小组警告说，在开放标签试验结束时，接受 GDNF 40周（9个月）的受试者和接受 GDNF 的受试者在症状改善方面没有显著差异。