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Innovative trial offers hope for recovery of brain cells damaged by Parkinson's disease


PICTURE: This is the GDNF delivery device.
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Credit: MintMotion for Passionate Productions

The results of a pioneering clinical trial program that provided experimental treatment directly to the brain give hope that it will be possible to restore damaged cells in Parkinson's disease.

The multi-million-pound study, funded by Parkinson UK with the help of The Parkinson's Cure & # 39; s Trust and in association with the North Bristol NHS Trust, aimed to determine whether increasing levels of a natural protein , the neurotrophic factor derived from the Glial cell line (GDNF), can regenerate the dying brain cells of people with Parkinson's disease and reverse their pathological condition, which no existing treatment can do.

In order for the GDNF to reach the brain cells that need it, a specially designed administration system has been developed. A total of 41 participants underwent robot-assisted surgery to insert four tubes carefully into their brains, which infused the GDNF directly into the affected brain areas with extreme accuracy, via a port located on the side of the head.

Six participated in the initial pilot study to assess the safety of the therapeutic approach. Thirty-five other individuals then participated in the nine-month double-blind trial, in which half of the patients were randomized to receive monthly infusions of GDNF and the other half placebo infusions. After the first nine months of treatment with GDNF or placebo, all participants had the opportunity to receive GDNF for nine additional months.

Although encouraging signs of improvement were observed in patients receiving GDNF, it was unfortunately not interesting to note a significant difference between the active treatment group and those receiving placebo when assessing symptoms of GDNF. Parkinson.

However, the results of brain tests have revealed extremely promising effects on damaged brain cells.

All participants had brain examinations before the start of the trial and after nine months to evaluate the functioning of their dopamine-producing brain cells.

After nine months, the placebo group analyzes did not change, while the group receiving GDNF showed a 100% improvement in a key area of ​​the brain affected by the disease – suggesting that treatment was starting to occur. wake. and restore damaged brain cells.

At 18 months, when all participants had received GDNF, symptom symptoms of both groups were moderate to significant compared to their scores prior to the start of the study. This provides further encouragement for the treatment to have long-term beneficial effects, but as everyone knew that they were receiving active treatment and that there was no comparison group, these improvements need to be treated with caution.

The results of these innovative tests are published today in Brain and the Journal of Parkinson's Disease.

The essay is also featured in an upcoming two-part documentary series on BBC Two – The Parkinson's Drug Trial: A Miracle Cure?

Dr. Alan Whone, principal investigator of the GDNF trial, said: "The spatial and relative improvement in brain scan enhancement exceeds anything we've seen before in administered growth factor therapy trials. Surgically for the treatment of Parkinson's disease, evidence that we may have a way to wake up and restore dopaminergic brain cells that are progressively being destroyed in Parkinson's disease.

"Its inability to produce the same effect on symptoms can be explained by a number of reasons.It is possible that the effects on symptoms are lower than the improvement of brain scans. double-blind may have produced a more distinct effect.

"It is also possible that a higher dose of GDNF would have been more effective or that participants at an early stage of the disease would have responded better.

"This is why it is essential to continue research on this treatment – GDNF continues to improve the lives of people with Parkinson's disease."

Dr Arthur Roach, Director of Research at Parkinson UK, said: "Although the results are unclear, this study is still a resounding success and has provided a better understanding of the potential effects of GDNF on damaged brain cells. It is possible to adopt a therapy in this way and deliver drugs precisely in the brain.

"All partners involved – including the scientific team, companies, charities and patients – continue to collaborate to explore possible avenues for further education." It is essential that we learn everything. what these recent tests could bring and that we wanted to work with the wider research community and people with Parkinson's disease so that future trials have the best chance of success. "

The test participant, Tom Phipps, 63, of Bristol, was the first person to undergo the pioneering surgical operation. He said:

"The clinical trials around Parkinson's are so important because it's a disease that will not go away unless people do the proper research.As a scientist myself – I'm a graduate in biological sciences – I wanted to contribute.

"During the trial, I found an improvement in my mobility and my energy, and I was even able to reduce my medications." Since then, I've slowly increased my drugs, but I continue to cycle, dig my allotment and chair the local branch of Parkinson's disease in the UK.

"My outcome was as positive as I would have liked.I think the lawsuit took me a long time and delayed the evolution of my condition.

"The best part was absolutely to be part of a group of people with a similar purpose – not only the team of consultants and nurses, but also the participants.

"You can not have expectations – you can only have hope."

Professor Steven Gill, lead neurosurgeon and device designer, commented: "This trial showed that we could safely and repeatedly infuse drugs directly into the patients' brains over months or years across a small implanted orifice that protrudes from the skin behind the ear is a significant advance in our ability to treat neurological conditions, such as Parkinson's disease, because most drugs that could act can not move from the bloodstream to the bloodstream. brain because of a natural protective barrier.

"Even at low doses, we have seen signs of patient improvement, which is extremely encouraging, and we need to move to a definitive clinical trial using higher doses, which requires urgent funding. this approach could be the first remedial treatment for people with Parkinson's disease, which is, of course, an extremely exciting prospect. "

Helen Matthews, Deputy Executive Director of The Cure Parkinson's Trust, said, "It's fantastic to see these encouraging results.This extremely complex test was able to be carried out thanks to the dedication of the whole community. team of participants, researchers, industry and charities.

"The Cure Parkinson & # 39; s Trust has been involved in the history of GDNF since 2003 through the commitment and determination of the late co-founder and president of this organization, Tom Isaacs.

"These results, particularly brain tests, show that GDNF, combined with improved convection technology, is a potential treatment for slowing, stopping, or even reversing Parkinson's disease, but it is essential that we focus now on how best to advance GDNF, understand whether a viable treatment could potentially regenerate dopamine cells and impact the lives of people with Parkinson's disease. "

Erich Mohr, president and CEO of MedGenesis, the biotechnology company at the head of GDNF, commented: "The results are not as clear as it would have been desirable, but when we look more closely, the disease Parkinson's is promising.

"In particular, when the scores of three of the key assessments are combined (motor response, activities of daily living and good quality" on time "), there is a very significant difference between treatment and placebo groups. Experimental Disease of Parkinson's Disease The composite response (PDCORE) can better capture all the effects of GDNF and we strive to validate it scientifically so that it can be used in future trials. "

Paul Skinner, general manager of neurological products at Renishaw, the engineering company that developed and built the device, said: "It was a privilege to work alongside the study team and with the participants in this ambitious essay.

"We are very encouraged by the changes in the brain tests, which demonstrates that the GDNF has an effect and that the administration system has allowed precise administration of drugs in the brain.

"This offers great potential for the use of the drug delivery system, developed by Renishaw, for future studies on Parkinson's disease and experimental treatments for other neurodegenerative diseases and tumors." brain."


For more information and interviews, please contact:

Amy Dodge, Head of Media and Public Relations, Parkinson's UK:

0207 932 1362 or 07961 460248 (out of hours)


Notes to editors

This press release highlights the conclusions of two articles published on Wednesday, February 27, 2019:

* "Randomized trial on neurotrophic factor derived from the intraputamenial and intermittent glial cell line in Parkinson's disease" – published in Brain: A Journal of Neurology.

"Prolonged treatment with a neurotrophic factor derived from the glial cell line in Parkinson's disease" – published in Journal of Parkinson's Disease.

Other case studies are available with images.

Image 1: Tom Phipps – Parkinson's UK Photo Credit

Image 2: Photo Credit – MintMotion for Passionate Productions

Video content is available, including:

a participant in the trial receiving an infusion https: //youtu.be/NGgqr_gu9lc

interviews with Tom Phipps and Renishaw, the company behind the device https: //youtu.be/cHnvke1p0VI

an animation to explain the project https: //youtu.be/PN5bJ-ookJk

Thank you for crediting Parkinson's UK.

The trial

Thirty-five people with Parkinson's disease participated in this nine-month, double-blind, placebo-controlled clinical trial of GDNF. Six other people were involved in the initial security phase.
To deliver GDNF to the appropriate brain region, an innovative delivery system, specifically designed for this task, called Convective Delivery (CED), was used. The participants were operated on so that four tubes were carefully placed in their brain. These were connected to a small port behind the ear to allow the GDNF to be pumped directly to the affected brain areas with extreme precision.

Participants traveled to Southmead Hospital every four weeks for treatment with GDNF or placebo, and for close monitoring and evaluation to measure the effects of their symptoms on treatment.

After the first nine months of treatment with GDNF or placebo, all participants had the opportunity to receive GDNF for nine additional months.

The study was completed in February 2017. All participants enrolled in the study completed it successfully. 99% of GDNF infusions were administered successfully and the study drug did not result in any serious side effects.

The partners

The study was funded by Parkinson UK, with support from The Parkinson's Cure & # 39; s Trust and in association with the North Bristol NHS Trust. MedGenesis Therapeutix has provided study medication, additional project resources, and additional funding. The latter has received some funding from the Michael J. Fox Foundation's Parkinson's Research Program. Renishaw plc manufactured the CED device on behalf of the North Bristol NHS Trust and provided additional technical and analytical support. The PET scanners were acquired by the PET Wales Research and Diagnostics Center at Cardiff University and analyzed by the PET Imaging Center at the University of British Columbia. More importantly, the researchers would like to express their gratitude for the contribution of the participants to the study.

The BBC documentary

The test on Parkinson's drugs: a miracle cure? will air on Thursday, February 28 at 9 pm on BBC Two and the second episode will air on Thursday, March 7 at 9 pm on BBC Two, subject to confirmation of television schedules.

About Parkinson's Disease

Every hour, two people in the UK are told that they have Parkinson's disease.

It affects 145,000 people in the UK, about one in 350 of the adult population.

Parkinson's disease is a degenerative neurological disease for which there is currently no cure. The main symptoms of the disease are tremors, slow movements and stiffness.

About Parkinson's disease in the UK

Parkinson's UK is the leading UK charity that supports people with this disease. Its mission is to find a cure and improve the lives of all people affected by Parkinson's disease through cutting-edge research, information, support and campaigns.

For tips, information, and support, visit http: // www.parkinsons.org.United Kingdom or call our toll-free, confidential helpline on 0808 800 0303.

About The Parkinson's Cure & # 39; s Trust

Cure Parkinson's Trust (CPT) has an ambitious goal: cure Parkinson's disease. More information on http: // www.cureparkinsons.org.United Kingdom

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