Researchers came up with an advanced device to deliver the drug MintMotion for Passionate Productions

A radical new treatment for Parkinson’s disease involves pumping drugs directly into the brain, but results from the latest trial can’t tell us whether it actually helps improve the lives of people with the condition.

Parkinson’s disease certainly needs better treatments. The condition, which involves tremors and problems walking and moving, is caused by the death of nerve cells that make dopamine, a signalling chemical in the brain. Medicines are available that top up dopamine levels, but they work less well as progressively more brain cells die and people can end up severely disabled.

GDNF (glial cell line-derived neurotrophic factor), helps to nurture brain cells including those that make dopamine. When the compound was discovered in the 1990s, animal tests led to high hopes that it would stop the root cause of Parkinson’s instead of just alleviating symptoms.


But its effects in people were inconsistent. Initial results were promising but when the compound was put to a real test – trials in which some people got the medicine and others got a placebo version – there was no difference.

This could have been down to the difficulty of getting the compound into the brain. So this latest trial used a sophisticated delivery system: four ultrathin tubes put into people’s heads to pump the compound to the site of the dopamine cells, a small brain structure called the putamen. “There was a lot of expectation on this trial,” says Roger Barker of the University of Cambridge, who was not involved in the work.

In the first stage of the study, 41 people got either GDNF or placebo for nine months. Brain scans showed that those on GDNF had more activity in their putamen. Parkinson’s UK, a charity that helped fund the trial, call this an “extremely promising effect”.

But what matters to people is not what shows up on a brain scan, but how severe their tremor is and whether they can walk. Sadly, by these measures, GDNF was no better than placebo.

The trial then continued for nine more months when both groups got GDNF. By the end, there were moderate to large improvements in their symptoms. That sounds promising, but the lack of control group in this stage means it could have been due to the placebo effect, which is pronounced in Parkinson’s.

The researchers suggest several reasons for the disappointing results in the placebo-controlled part of the trial. Perhaps physical benefits lag behind the changes seen on brain scans and the trial didn’t last long enough. Perhaps too low a dose was given, or people were at too advanced a stage of their illness; you can’t preserve dopamine cells if they are already dead.

All of these explanations are plausible, but they cannot make up for the fact that yet another trial of GDNF has failed to show it works. “Some hope there’s still mileage in this treatment. Others see this as the final nail in the coffin,” says Barker.

MedGenesis, the Canadian firm that owns GDNF, has been planning a further larger trial, necessary before the compound could be sold as a medicine. Although the company said the results show signs of promise, it also admits they are “not as clear-cut as would have been desirable”. The firm has not yet secured funding for the trial and these kind of results won’t help.

“These studies potentially open the door to a viable means by which to repeatedly administer potentially disease modifying therapies, direct to targeted brain structures, as they become available, to people with a host of neurodegenerative conditions or brain tumours in the future,” says Alan Whone at the University of Bristol, UK, who led the work.

“Despite the disappointment of not reaching the primary or secondary endpoints there remains hope that a potential rational for leveraging the learnings from these recent studies into a future confirmatory GDNF trial is yet possible.”

Journal reference: Brain, DOI: 10.1093/brain/awz023

Since this article was first published we have added comment from Alan Whone and clarified the implications of the results we reported