First hints Parkinson's can be stopped

Authored by bbc.com and submitted by mvea

It may be possible to stop the progression of Parkinson's disease with a drug normally used in type 2 diabetes, a clinical trial suggests.

Current drugs help manage the symptoms, but do not prevent brain cells dying.

The trial on 62 patients, published in the Lancet, hints the medicine halted the progression of the disease.

The University College London (UCL) team is "excited", but it urges caution as any long-term benefit is uncertain and the drug needs more testing.

"There's absolutely no doubt the most important unmet need in Parkinson's is a drug to slow down disease progression, it's unarguable," Prof Tom Foltynie, one of the researchers, told the BBC.

In Parkinson's, the brain is progressively damaged and the cells that produce the hormone dopamine are lost.

It leads to a tremor, difficulty moving and eventually memory problems.

Therapies help manage symptoms by boosting dopamine levels, but the death of the brain continues and the disease gets worse.

In the trial, half of patients were given the diabetes drug exenatide and the rest were given a placebo (dummy treatment). All the patients stayed on their usual medication.

As expected, those on just their usual medication declined over 48 weeks of treatment. But those given exenatide were stable.

And three months after the experimental treatment stopped, those who had been taking exenatide were still better off.

Prof Foltynie told the BBC News website: "This is the first clinical trial in actual patients with Parkinson's where there has been anything like this size of effect.

"It gives us confidence exenatide is not just masking symptoms, it's doing something to the underlying disease.

"We have to be excited and encouraged, but also cautious as we need to replicate these findings."

They also need to trial the drug for much longer periods of time.

An effective drug would need to hold back the disease for years in order to make a significant difference to patients.

Parkinson's progresses slowly and the difference in this 60-week trial was definitely there, but was "trivial" in terms of the impact on day-to-day life, say the researchers.

The drug helps control blood sugar levels in diabetes by acting on a hormone sensor called GLP-1.

Those sensors are found in brain cells too. It is thought the drug makes those cells work more efficiently or helps them to survive.

It is why the drug is being tested in other neurodegenerative diseases including Alzheimer's.

David Dexter, the deputy director of research at Parkinson's UK, said: "The findings offer hope that drugs like exenatide can slow the course of Parkinson's - something no current treatment can do.

"Because Parkinson's can progress quite gradually, this study was probably too small and short to tell us whether exenatide can halt the progression of the condition, but it's certainly encouraging and warrants further investigation."

Dr Brian Fiske, from the The Michael J Fox Foundation for Parkinson's Research, said: "The results from the exenatide studies justify continued testing, but clinicians and patients are urged not to add exenatide to their regimens until more is known about their safety and impact on Parkinson's."

Sanpaku on August 5th, 2017 at 16:01 UTC »

Who would have thought to look here:

Exenatide is a synthetic version of exendin-4, a hormone found in the saliva of the Gila monster that was first isolated by John Eng MD in 1992.

hutima on August 5th, 2017 at 13:36 UTC »

is this better than existing medications or worse. There may be an absolute improvement over placebo in the journal but that doesn’t mean it is better than existing medicine

edit: having more closely read the paper, it was taken in with existing meds which is a lot more promising than I originally thought

mvea on August 5th, 2017 at 11:27 UTC »

Journal reference:

Exenatide once weekly versus placebo in Parkinson's disease: a randomised, double-blind, placebo-controlled trial

Dilan Athauda, MRCP, Kate Maclagan, PhD, Simon S Skene, PhD, Martha Bajwa-Joseph, PhD, Dawn Letchford, Kashfia Chowdhury, MSc, Steve Hibbert, MBA, Natalia Budnik, Vrach, Luca Zampedri, MSc, John Dickson, PhD, Yazhou Li, PhD, Iciar Aviles-Olmos, PhD, Prof Thomas T Warner, FRCP, Prof Patricia Limousin, MD, Prof Andrew J Lees, FRCP, Nigel H Greig, PhD, Susan Tebbs, MSc, Prof Thomas Foltynie, PhD'

The Lancet

Published: 03 August 2017

DOI: http://dx.doi.org/10.1016/S0140-6736(17)31585-4

Link: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31585-4/fulltext

Summary:

Background

Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has neuroprotective effects in preclinical models of Parkinson's disease. We investigated whether these effects would be apparent in a clinical trial.

Methods

In this single-centre, randomised, double-blind, placebo-controlled trial, patients with moderate Parkinson's disease were randomly assigned (1:1) to receive subcutaneous injections of exenatide 2 mg or placebo once weekly for 48 weeks in addition to their regular medication, followed by a 12-week washout period. Eligible patients were aged 25–75 years, had idiopathic Parkinson's disease as measured by Queen Square Brain Bank criteria, were on dopaminergic treatment with wearing-off effects, and were at Hoehn and Yahr stage 2·5 or less when on treatment. Randomisation was by web-based randomisation with a two strata block design according to disease severity. Patients and investigators were masked to treatment allocation. The primary outcome was the adjusted difference in the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor subscale (part 3) in the practically defined off-medication state at 60 weeks. All efficacy analyses were based on a modified intention-to-treat principle, which included all patients who completed any post-randomisation follow-up assessments. The study is registered at ClinicalTrials.gov (NCT01971242) and is completed.

Findings

Between June 18, 2014, and March 13, 2015, 62 patients were enrolled and randomly assigned, 32 to exenatide and 30 to placebo. Our primary analysis included 31 patients in the exenatide group and 29 patients in the placebo group. At 60 weeks, off-medication scores on part 3 of the MDS-UPDRS had improved by 1·0 points (95% CI −2·6 to 0·7) in the exenatide group and worsened by 2·1 points (−0·6 to 4·8) in the placebo group, an adjusted mean difference of −3·5 points (−6·7 to −0·3; p=0·0318). Injection site reactions and gastrointestinal symptoms were common adverse events in both groups. Six serious adverse events occurred in the exenatide group and two in the placebo group, although none in either group were judged to be related to the study interventions.

Interpretation

Exenatide had positive effects on practically defined off-medication motor scores in Parkinson's disease, which were sustained beyond the period of exposure. Whether exenatide affects the underlying disease pathophysiology or simply induces long-lasting symptomatic effects is uncertain. Exenatide represents a major new avenue for investigation in Parkinson's disease, and effects on everyday symptoms should be examined in longer-term trials.