Below is a summary of key things Dr David Breen discussed. David is a Senior Clinical Research Fellow and Honorary Consultant Neurologist, based at Centre for Clinical Brain Sciences, Anne Rowling Regenerative Neurology Clinic.
David began by outlining ACT-PD. In order to explain properly, Cure Parkinson’s information is given below (paraphrased unless quoted): ACT-PD stands for Accelerating Clinical Treatments for Parkinson’s Disease. The project is also known as the Edmond J. Safra ACT-PD Initiative (or EJS ACT-PD)
The leadership team of the project includes, among others, Dr Camille Carroll who presented the Edinburgh Parkinson’s Lecture 2024.
The aim of the project is to set up a MAMS platform for evaluating potentially disease modifying therapies for Parkinson’s.
Cure Parkinson’s confirm “A Multi-Arm Multi-Stage (or MAMS) clinical trial is a study that allows for the assessment of several potential therapies at the same time. It also shifts participants seamlessly from a Phase II (safety and efficacy) study to a Phase III trial, by regular within study measures (or interim analyses)”.
David mentioned a couple of other established projects:
MND-SMART: An innovative clinical drugs trial testing potential new treatments that may slow, stop or reverse the progression of MND. This is a multi-arm trial, which means MND-SMART will test more than one at the same time. The Ann Rowling Regenerative Neurology Clinic are currently seeking recruits.
Octopus trial for progressive MS: is described as being designed to be a more efficient kind of clinical trial by using the multi-arm, multi-stage (MAMS) approach (source: Multiple Sclerosis Trust).
David confirmed ACT-PD is going to be a coordinated approach UK wide that will mean more opportunities for taking part in the UK. 45 sites are identified, including NHS Lothian (though their remit will expand to Fife and Forth Valley, maybe as far as Borders).
He then outlined drug repurposing which involves finding new uses for existing, approved drugs. This is not necessarily a new concept. Aspirin was initially marketed as an analgesic, and later repurposed as an antiplatelet aggregation drug. With Thalidomide, later research revealed the diverse effects of thalidomide, leading to its repositioning for multiple myeloma and other types of tumours. (Source)
Some of the drug candidates, potentially accelerating drug development and addressing unmet medical needs were outlined by David:
Telmisartan: originally developed as an antihypertensive (blood pressure) drug, is being explored for repurposing for conditions like breast cancer and Alzheimer’s disease
Terazosin: a drug commonly used for high blood pressure and enlarged prostates, is being explored as a potential treatment for motor neuron disease (MND)
UDCA: (Ursodeoxycholic acid): Cure Parkinson’s research looks to evaluate if this is a safe and tolerable treatment for people with Parkinson’s.
Istradefylline: is primarily used for Parkinson’s but was also under development for other conditions like major depressive disorder, restless legs syndrome, and substance-related disorder (Source)
David said that all these feed into the programme and there are a couple more in the pipeline. He confirmed that in doing the research a double-blind placebo control is the format for clinical trials.
David outlined NeuroCARE, the Anne Rowling Regenerative Neurology Clinic platform for people in Scotland with a neurological condition, and their carers, to sign up to help research and find out about opportunities to take part in studies and trials. David confirmed that currently the Western General Hospital tends to be where trials are done. But potentially Ann Rowling Clinic may be where some will take place going forward. He also confirmed it is about 4-6 months until the study begins. ACT-PD has the widest of the recruitment options, but it likely will not those who have dementia, or have had DBS.
As mentioned earlier, Camille Carroll is a principal investigator.
David talked about different subgroups of Parkinson’s, and different ways on which it leads to or manifests in PD. These include protein aggregation, and potentially mitochondrial disfunction.
Ambroxol Study (ASPro)
David outlined that the first participant has received either ambroxol or the placebo in the ASPro-PD trial. NHS Lothian we will be one of 15 sites testing this, against placebo. Ambroxol is a cough suppressant that can stimulate an enzyme that PD sufferers are lacking in.
Parkinson’s UK confirm “Ambroxol boosts levels of an enzyme called GCase, which is known to help clear away waste products which have gathered in brain cells. In Parkinson’s, a build up of a troublesome protein called alpha-synuclein is often seen in the brain tissue. It’s thought that ambroxol may help improve the body’s ability to clear away these clumps of alpha-synuclein and prevent damage to brain cells”.
The trial starts later this year. It is a 2 year study. Respondents have their GBA status checked. A GBA test is used to identify mutations in the GBA1 gene. This gene is associated with Gaucher disease and can also be a risk factor for Parkinson’s disease. The test helps determine if an individual has Gaucher disease, is a carrier of a GBA1 variant, or has an increased risk of developing Parkinson’s disease.
The PD Frontline study will send saliva kit and do the genetic status. Parkinson’s UK are carrying out research is to find a large number of people who have small genetic changes in genes such as LRRK2 or GBA, which are known to be associated with Parkinson’s (Source).
David confirmed that disease mutation in PD can happen. Knowing if one is a GBA carrier can be useful. Different mutations can increase the likelihood of PD in the children of PwPs.
