Skip links

SydneyDBS

Header Right

Blog

By

Australian Parkinson’s Mission (APM) summary

The Australian Parkinson’s Mission (APM) is an Australian-based, international collaboration involving a revolutionary clinical trial design using potential repurposed drugs as well as genomics research.

Update on the APM study by National Trials Lead, Professor Simon Lewis.

Approximately 100,000 people live with Parkinson’s Disease in Australia, with a further 14,000 diagnosed each year.

Current PD treatments target symptoms of the disease, rather than preventing disease progression. APM aims to develop a framework over the next five years to promote effective and individualised treatments to slow the disease progression for Parkinson’s patients.

APM Collaborators

  • Michael J Fox Foundation (USA)
  • The Cure Parkinson’s Trust (UK)
  • Garvan Institute of Medical Research
  • Shake It Up Australia Foundation
  • Parkinson’s Australia
  • The University of Sydney

About the APM study

Recruitment will commence in March 2020. Recruitment is open to people with Parkinson’s disease, including newly diagnosed and those who have been living with the disease for some time.

Recruitment sites will initially commence in the main cities within Victoria, New South Wales and Queensland, with plans to extend recruitment to Australian regional centres.

Participants in the study will undergo genetic and biomarker analysis so that researchers can classify genetic variations specific to their disease. Participants will then be enrolled in trials utilizing repurposed drugs proposed to have a disease modifying effect in Parkinson’s disease.

The benefits of using repurposed drugs is that they have already gone through the expensive and time-consuming clinical trials to get them to market. One of the aims of APM is to offer a faster process from lab to market for people with PD.

Potential benefits of the study include;

  • Measurement of disease progression through biomarker analysis
  • Individualisation of drug treatment for PD patients
  • Protocol development for screening and early intervention of people at high risk of PD
  • Development of a PD sub-classification based on patients’ DNA

For more information, go to www.theapm.org.au, contact the APM via email at info@TheAPM.org.au or phone 1300 770577.

Links to partner websites as follows:

www.shakeitup.org.au

https://www.garvan.org.au/

https://www.michaeljfox.org/

http://www.cureparkinsons.org.uk

https://www.parkinsons.org.au/

https://sydney.edu.au/

http://www.profsimonlewis.com/

By

Current Repurposed Drug Trials in Parkinson’s Disease

Drugs that once treated conditions such as type 2 diabetes, cancer, high cholesterol and dementia are now being evaluated in repurposed drug trials in Parkinson’s disease. To find out more, you can read our summary here.

What is a repurposed drug?

A repurposed drug is a drug that has been developed to treat one type of disease, but is being utilised in the treatment of another disease.

The benefits of repurposed drugs are that they have already gone through the expensive and time-consuming clinical trial process to get them to market. Therefore, they can be less costly to develop and more readily available than novel therapies.

Many repurposed drug trials are currently underway in Parkinson’s disease. Examples include:

  • Exenatide – a drug currently used to treat type 2 diabetes, acts on the GLP-1 receptors in the pancreas and brain. Promising research from the UK has shown improvements in motor symptoms of PD in those participants receiving Exenatide, however more research is needed.
  • Liraglutide and lixisenatide – are newer drugs that also treat type 2 diabetes. Initial rodent studies found these drugs were more effective at preventing brain cell death than Exenatide. Currently, there are two trials underway to investigate the effects of these drugs on PDin the US and France.
  • Statins – are often prescribed to help lower cholesterol in people at risk of cardiovascular disease. Research in rodent models suggest statins have protective effects on PD progression, such as; reducing inflammation, oxidative stress damage, as well as reducing the build-up of alpha-synuclein proteins. Currently, a randomised control trial is underway in the UK to assess the effectiveness of a statin – Simvastatin on PD symptoms in 235 patients with mild PD symptoms.
  • Ursodeoxycholic acid (UDCA) – a drug typically used to treat liver disease has been implicated in the restoration of mitochondrial cells (which fuel our cells) in a UK based study. Impairments in mitochondrial function are a key contributor to brain cell death in PD.
  • Nilotinib – used traditionally to treat a form of leukaemia, however recent research has found Nilotinib reduces brain cell death by binding to specific proteins in the brain. A 2015 study found patients who took Nilotinib had a reduction in PD-related motor symptoms.
  • Deferiprone – is used to treat people with excess iron, a common symptom of PD, thought to be due to excess iron found in dopamine-producing brain cells. Promising research from animal models has led to a current European-based trial with over 300 participants to investigate Deferiprone in slowing the progression of PD.
  • Isradipine – is used to treat high blood pressure. It works by blocking the uptake of calcium into cells. Research has found Isradipine also works on dopamine-producing brain cells, leading to reduced calcium uptake and subsequent oxidative damage. A multi-centre clinical trial involving 336 newly diagnosed PD patients is currently underway across the US and Canada. The trial is expected to finish at the end of 2019.
  • Ambroxol – typically used as a cough medication to help reduce the build-up of mucus, has had positive effects in the treatment of PD through increasing the activity of a protein called glucocerebrosidase (or GCase), which control alpha-synuclein levels – a key protein implicated in PD. Current research is underway in the UK and Canada to investigate Ambroxol in PD patients.
  • Rivastigmine – is currently used to treat dementia but has shown promise in PD patients via its ability to increase acetylcholine levels, implicated in memory and concentration. A UK-based study recruiting 600 PD patients is currently underway to investigate the effect Rivastigmine has on PD symptoms.

Repurposed drug trials will soon be commencing in Australia through the Australian Parkinson’s Mission. See our next blog for further information.

The information provided in this article is of a general nature only and is not treatment advice. Recommendations regarding therapy can only be made on a case by case basis, discussed between a patient and their treating doctor/s.

The information in this article was current at December 2019.

By

How Common is Parkinson’s Disease?

How common is Parkinson’s disease? A new meta-analysis provides insight into the prevalence of the disease, looking at prevalence in age, sex and location. Interested to learn more? Read our summary here.

The prevalence of Parkinson’s Disease increases steadily with age, according to research published in the journal Movement Disorders.

Analysing worldwide data from 47 studies published from 1985 to 2010, a European research team studied data by age group, geographic location, and sex.

Because it included data from a large number of studies, this meta-analysis provided a valuable insight into how common Parkinson’s Disease really is. 

Specifically, the research team identified the following findings:

A ‘rising prevalence’ of PD with age

The researchers found that Parkinson’s Disease affected:

  • 40 to 49 years – 41 people in 100,000
  • 50 to 59 years – 107 people in 100,000
  • 55 to 64 years – 173 people in 100,000
  • 60 to 69 years – 428 people in 100,000
  • 65 to 74 years – 425 people in 100,000
  • 70 to 79 years – 1087 people in 100,000
  • Older than age 80 – 1903 people in 100,000

A ‘significant difference’ in prevalence by geographic location

For people aged 70 to 79, the researchers found that 1,601 people from North America, Europe, and Australia had Parkinson’s Disease – compared with 646 in individuals from Asia (P< 0.05).

Parkinson’s disease prevalence varies by gender, but only for people aged 50 to 59

A significant difference in prevalence by sex was found only for individuals 50 to 59 years old, with a prevalence of 41 in females and 134 in males (P< 0.05). ie PD is more common in men in the 50-59 year old age group.

 “These findings argue for further epidemiologic surveys, specifically with high-quality screening instruments for Parkinson’s Disease and confirmation of diagnoses with sensitive, internationally accepted diagnostic criteria to ensure greater

Comparability,” the researchers wrote.

The researchers argue that longer-term prospective studies would help establish whether the clinical progression and prognosis of the disease differs between racial groups and among different parts of the world.

The team also hope that demonstrating reliable differences in prevalence can provide opportunities for more refined studies that might provide information as to how a patient’s genes or environmental factors influence disease susceptibility, progression and treatment response.

Further, the research team noted the importance of Prevalence studies in assisting Governments and Health services to plan appropriate treatment resources for PD in the context of an aging population.

Summary of the article here https://www.ncbi.nlm.nih.gov/pubmed/24976103

By

Drs Cook & Silberstein feature on the cover of the North Shore Times/Mosman Daily

Neurosurgeon Dr Raymond Cook and Neurologist Dr Paul Silberstein feature on the cover of the North Shore Times/Mosman Daily in the story ‘Brains trust: The north shore team taking the fight to Parkinson’s disease’.

The story talks about the work both doctors do for people that are living with Parkinson’s disease and features an interview with a Parkinson’s patient, Carole McFadden, whose life has profoundly changed after recently having deep brain stimulation surgery at North Shore Private Hospital.

Shake it Up Australia Foundation founder, Clyde Campbell, also discusses the journey that led him to launch the foundation, and the impressive work they do to fund medical treatments with the aim of finding a cure for Parkinson’s disease.

The full story can be accessed online at http://newslocal.smedia.com.au/north-shore-times. Click on ‘back issues’ to access archived editions of the weekly newspaper.

By

Device assisted therapies for treatment of patients with Parkinson’s disease

In a recent study, researchers investigated the clinical effectiveness of three different device-assisted therapies for people with Parkinson’s Disease experiencing motor fluctuations and dyskinesias. The team found beneficial effects of all three treatment options. Keen to find out more? Read our summary here.

Device assisted therapies for treatment of patients with Parkinson’s disease 

In the early stages of PD, most patients experience substantial benefit with medical therapy and exercise, achieving a 60-80% improvement of physical symptoms with consistent control through the day. 

Over years, however, symptom control can become inconsistent and is sometimes accompanied by periods of excessive movement called ‘dyskinesia’. 

Medication adjustments can be effective in ironing out these motor fluctuations and dyskinesia, however in the longer term, some patients find that consistent symptom control cannot be achieved even after altering their medications. 

At this stage, a second tier of therapies can be effective in regaining consistent control of Parkinson’s symptoms and reducing dyskinesia. These therapies are delivered by medical devices and are collectively referred to as ‘Device Assisted Therapies’. 

Currently, there are three device assisted therapies with proven efficacy in patients with motor fluctuations and dyskinesias: 

· Deep Brain Stimulation (DBS) 

· Apomorphine infusion (Apo) 

· Intrajejunal levodopa infusion (IJLI) 

Whilst all three therapies have been examined using the gold standard study format for medical interventions (a blinded randomised placebo controlled trial), head to head comparisons of all three therapies have not been previously performed. 

In a recent study, researchers investigated the clinical effectiveness of the three different device-assisted therapies for people with Parkinson’s Disease experiencing motor fluctuations and dyskinesias. 

The researchers observed 173 people in total who were undergoing: 

· Bilateral subthalamic stimulation (STN-DBS) – 101 people 

· Apomorphine (APO) – 39 people 

· Intrajejunal levodopa infusion (IJLI) – 33 people. 

The research, which is the first real-life comparison in people with Parkinson’s Disease undergoing device assisted therapies was published in the journal Movement Disorders. Link to summary here https://www.ncbi.nlm.nih.gov/pubmed/30719763 

Importantly, the study examined and compared the effects of the three therapies on a broad range of PD symptoms aswell as quality of life. Specifically, the study examined and compared the effect of each of the therapies on: 

· Physical (motor) symptoms 

· Non-motor symptoms (cognition, mood, bladder and bowel, sleep disturbance & pain) 

· Quality of Life 

As had been demonstrated in earlier studies, all three therapies were effective in reducing motor fluctuations and dyskinesias and improving quality of life. Each therapy was however associated with a different profile of improvement of non-motor symptoms 

· STN-DBS improved urinary and sexual functions, mood/cognition, sleep/fatigue, and the miscellaneous domain (pain, sense of taste and smell, weight change, excessive sweating) 

· IJLI improved the mood/cognition, sleep/fatigue, miscellaneous and gastrointestinal symptoms. 

· APO improved mood/cognition, perceptual problems/hallucinations, attention/memory, and the miscellaneous domain. 

“Our results highlight the importance of holistic assessments of motor as well as nonmotor aspects of Parkinson’s Disease that could provide a means to personalise treatment options to patients’ individual Parkinson’s Disease profiles,” the researchers wrote. 

This work assists clinicians in providing optimal recommendations regarding device assisted therapies, taking into account the full profile of an individual patient’s symptoms.

By

The novel GDNF trial yields mixed results

The novel GDNF clinical trial offered hope for restoring brain cells in people with Parkinson’s Disease. Including 41 people with Parkinson’s Disease aged between 41 and 72, the clinical trial was designed to investigate whether GDNF could slow, stop or reverse Parkinson’s Disease. Results were recently published. Read our study summary here.

Neurotrophic factors are small proteins produced in the brain that support the growth, survival and differentiation of brain cells. These proteins are important for maintenance of brain health and consequently there has been considerable interest in whether these proteins might improve survival or indeed assist regeneration of brain cells that are affected by Parkinson’s disease. 

From 2012 to 2017, UK researchers conducted a novel clinical trial looking at the effects of delivering one such Neurotrophic factor, Glial Derived Neurotrophic Factor (GDNF) directly to the brain, using a new type of surgically implanted device. Link to article here https://www.parkinsonsmovement.com/the-gdnf-trial/ 

Including 41 people with Parkinson’s Disease aged between 41 and 72, the clinical trial was designed to investigate whether GDNF could slow, stop or reverse Parkinson’s Disease. 

The group, all of whom had been diagnosed around eight years ago, were split into two smaller groups who were allocated either a placebo or the GDNF treatment. 

Using a device mounted on the skull, the researchers were able to directly infuse GDNF into the putamen – an important brain region that is affected by PD. Study participants received either placebo or GDNF treatment every four weeks for 40 weeks. 

After the 40-week period, the researchers noted that there was “no overall difference between the GDNF and placebo group” in terms of their movement scores. However, nine people showed what researchers called a “clinically significant improvement”. 

The researchers then conducted an extension study for an additional 40 weeks and again found no clear difference between patients who had received GDNF versus placebo. 

Overall, neither the GDNF study nor the extension study helped to improve movement-related symptoms in people with Parkinson’s, ultimately leading to the conclusion that GDNF infusions at the dose and for the duration used did not improve Parkinson’s disease. 

Despite these disappointing results, the study demonstrated that direct monthly brain infusions of substances that might treat Parkinson’s disease is feasible and tolerable, thus providing an important platform for future trials into possible therapies for Parkinsons’s disease. 

A documentary regarding this trial has been produced by the BBC: https://www.bbc.com/news/av/stories-47483307/the-radical-drug-trial-hoping-for-a-miracle-parkinson-s-cure