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Clinical Science II – Simon Stott

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What’s new on drug repurposing

Hi everyone my name is simon and i’m the deputy director of research at cure parkinson’s and i’d like to thank the world parkinson’s coalition for inviting me here today to talk to you about what is new with regards to drug repurposing for parkinson’s disease now the first question to ask is what do we mean when we talk about drug repurposing drug repurposing is

Basically a means of speeding up the traditional drug development process by evaluating clinically available therapies in new medical conditions the traditional drug development process is long and time consuming it starts off with a target protein and then you will look and screen for molecules that can target that target protein and after you’ve done that then

You’ll start to do medicinal chemistry to improve that molecule give it better properties and then you’ll start testing that molecule in animal models of your condition of interest doing checking the metabolism the toxicology the tolerability of the before you start shifting across into clinical studies testing the molecule in humans now by drug repurposing

What you can do is that you know a lot already about a lot of the drugs that are used in the clinic we know a lot about their safety their tolerability in humans so we can skip over that medicinal chemistry step we can skip over the animal model modeling and tolerability and metabolism research and we can go directly into testing the drugs in humans so we’re

Taking five to ten years off that drug development process and jumping straight into testing on humans speeding up that drug development process so a good example of a drug that’s being repurposed for parkinson’s is the diabetes drug called by during or also known as xenotide it’s a geo it’s called a glp1 agonist so glp1 is the protein that is the receptor that is

Targeting and preclinical data suggested that this drug by urine is having beneficial effects and models of parkinson’s and the phase 2 trial was set up and run and the results were reported in 2017 suggested that this drug was also having beneficial effects with regards to the motor symptoms of parkinson’s as you can see in the graph presented on the slide here

The red line demonstrates a group of individuals 30 individuals who are treated with a placebo treatment and you can see that they gradually progress in their parkinson’s symptoms whereas the blue group uh these were 30 individuals who were treated with by urine for 48 weeks and you can see that they immediately improve in their motor symptoms and they stabilize

Across the rest of the 48 week period so this was an encouraging result for the parkinson’s research community and a phase 3 study has now been set up and has been conducted in the uk where we are recruiting 200 individuals with parkinson’s and they’ll be treated either with placebo or with by urine for two years and they’ll be assessed over that period of time and

Hopefully if the results pan out this will be a new drug that can be used for the treatment of parkinson’s in the very near future and this study this program was supported recently by some epidemiological data which suggested that people who are with living with diabetes and are treated with examination have a reduced risk of developing parkinson’s in the long

Term compared to people with diabetes who are not being uh treated with exenatide so uh some further support for repurposing this drug for parkinson’s another drug another example of a drug that’s being repurposed for parkinson’s is terazosin this is a drug that’s used for the treatment of enlarged prostates but last year a group of researchers at iowa university

And collaborators published results suggesting that this drug was having beneficial effects in models of parkinson’s by boosting the cellular energy levels and this was resulting in neuroprotective effects a phase two a phase one two study was set up immediately to test the safety and tolerability of the drug in people with parkinson’s that study is now completed

And we’re waiting on the results um but while we’re waiting the researchers are continuing um to develop this program by looking at target engagement in another in another cohort of individuals and very recently they’ve published further data based on analyses of a medical database which suggested that people who have been treated with terazosim over the long

Term have a reduced risk of developing parkinson’s so again further support for developing for repurposing this drug parkinson’s a third example of a drug being repurposed for parkinson’s is ambroxol this is a widely used respiratory medication so it’s used for inflammation of the throat and lungs and a phase two study was um set up after some pre-clinical data

Suggested that this molecule was boosting levels of a key enzyme a key parkinson’s related enzyme called g-case in the brain and this phase two study was conducted and last year we learned the results of that study which suggested that ambroxil was well tolerated in people with parkinson’s at a much higher dose than what’s used for its typical throat and chest

Conditions and so it was well tolerated it was safe for six months and it also increased levels of this enzyme g case in the brain of these individuals so these were encouraging results and we’re now looking at setting up a phase three trial for um ambroxil a fourth example of a drug that’s being repurposed for parkinson’s is a lot of drugs being repurposed for

Parkinson’s but a fourth example is udca this is a secondary bile acid that typically is used in the clinic for the treatment of gallstones it helps to break down gallstones and improve liver function uh preclinical data suggested that uh this um drug was having uh positive effects in models of parkinson’s boosting um the performance of mitochondria these are

The power stations of our cells in our body they provide all the energy so udca was improving the function of mitochondria and then the phase ii study was set up a clinical trial in sheffield here in the uk and also in london uh that study has now been completed and we’re waiting on the results um which will be hopefully available later this year um and it’ll

Be interesting to see um whether we see a positive effect there or not and whether this drug is taken forward for further evaluation and parkinson’s one other topic to mention with regards to drug repurposing and parkinson’s is the australian parkinson’s mission so this is a large clinical trial program set up by the australian federal government in which they

Are spending 30 million dollars on multi-armed clinical trials so these trials are involving lots of hundreds of people and they’ll be divided into separate groups uh separate arms you could call them of a study and each group will be treated with one particular repurposed drug and one group will be treated with placebo and all that none of these individuals will

Know which drug or they’re being treated with but it might be placebo or might be one of the repurposed drugs but they’ll be followed over a year with clinical assessments etc and the purpose here is to look at multiple drugs at the same time to determine which of these drugs could be effective as opposed to just doing one police seat one drug versus one placebo

One drug versus one placebo this is a means of speeding up the drug repurposing program uh process excuse me and um the first trial the first multi-armed trial in the australian parkinson’s mission is up and running now and they are in the process of setting up a second and third study as well so that’ll be something to look out for in the near future so just

To summarize drug repurposing represents a means of speeding up the traditional drug development process by evaluating clinically available therapies in new medical conditions and we’ve looked at a few examples of drugs that are being repurposed for parkinson’s by urine tyrosine and broxol udca and also a novel uh platform for testing uh repurposed drugs in the

Form of the australian parkinson’s mission and with that i’d just like to say thank you very much and i’ll be happy to address any questions you might have in the q a session thank you very much

Transcribed from video
Clinical Science II – Simon Stott By World Parkinson Coalition