Trials to treatments: repurposed drugs

What if a diabetes drug could slow down Parkinson’s, or a dementia drug could reduce falls? In this blog, we find out what drug repurposing means and take a look at drugs with potential for Parkinson’s.

Claire Bale
Aug 6, 2018 · 11 min read
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Developing a new drug from scratch is a long, slow and expensive process.

Using drugs designed to treat one condition for another unrelated one may sound like an odd concept, but it’s actually something that’s happened in medicine for decades. And it’s even got a name — drug repurposing.

One unlikely but powerful example of repurposing is thalidomide. Infamous for the tragic birth defects it caused in the 1950s, when it was used by expectant mothers as a treatment for morning sickness, you’d be forgiven for thinking that thalidomide was well and truly on the scrapheap. But, actually thalidomide is now an important treatment for leprosy and multiple melanoma (a form of bone cancer).

One example we already have in Parkinson’s is apomorphine — a fast-acting dopamine agonist that tends to be used in later stages of the condition. But apomorphine is a very old drug and its original uses were very different. As far back as the 1870s, apomorphine was used in small doses as one of the first treatments for alcoholism as it helped to reduce alcoholic cravings. It was not until 100 years later, in the 1970s, that it began to be used for Parkinson’s.

But why do drugs have these multiple and seemingly unrelated uses?

Drugs work by entering the body and altering the way cells work. They often do this by interacting with a protein that plays a particular role in the illness.

But, our bodies are made up of thousands of proteins, and each individual type of protein may appear in various places in the body and have a range of different jobs to do.

This can be a problem because it’s difficult to control where drugs to travel to inside the body. This means when you develop a drug to interact with a protein in one organ — say the lungs — you often find that the drug ends up in other places in the body where this protein is also active. When this happens the drug can interfere with the normal function of cells and cause unwanted side effects.

However, this interference is a double-edged sword. Sometimes, when drugs end up where they’re not supposed to be, they can have unexpectedly positive effects — and it’s these serendipitous benefits that repurposing seeks to harness.

The beauty of repurposing is, when hidden benefits of drugs that are already approved are found, often fewer lab studies and clinical trials are needed. This means repurposing has the potential to deliver new and better treatments much more quickly, easily and cheaply.

Why do we need to do clinical trials at all if these drugs are already available and known to be safe?

Even approved drugs have potential risks and side effects.

Repurposing them for Parkinson’s could mean using them in a group of people who they’ve never been tested in. It may also mean taking them at higher doses, for longer periods of time, and in combination with Parkinson’s medications.

These are all factors that need to be carefully investigated in clinical trials in people with the condition to ensure we fully understand the benefits and the risks, before they can be made available.

Diabetes drugs are leading the way

One of the most fruitful avenues for repurposing so far has been diabetes, and in particular, drugs that target a particular receptor called glucagon-like peptide 1 (GLP-1).

GLP-1 is a hormone that is produced when we eat or drink. It triggers the release of insulin, which helps us absorb glucose from the blood. Drugs that mimic the effects of GLP-1 are very important for helping people with type 2 diabetes to manage their blood-sugar levels.

But GLP-1 has more far-reaching effects than just stimulating insulin.

Research has shown that receptors which recognise and respond to GLP-1 are also present in the brain, and stimulating these receptors can have positive effects on a host of important functions that help to keep brain cells healthy and working well. What’s more, studies in cells and animals in the lab suggest that drugs that target GLP-1 receptors could have neuroprotective effects in Parkinson’s. This means they could have the power to slow the relentless damage to dopamine-producing brain cells, and therefore delay the deterioration of symptoms.

This has led to a number of clinical trials to test whether existing drugs for diabetes could produce the same kind of effects in people with Parkinson’s — and several different drugs are currently being tested in clinical trials.

Exenatide (also known as Bydureon or Byetta)

Exenatide is without doubt the frontrunner. It has already been tested in two clinical trials, both carried out by researchers at University College London.

Results have shown promise that treatment may help to slow the progression of Parkinson’s, but have not been sufficiently conclusive.

Further, more powerful studies are now being planned that aim to provide a fuller understanding of the effects of exenatide for people with Parkinson’s.

New kids on the block: lixisenatide and liraglutide

Liraglutide and lixisenatide are newer diabetes drugs that also act on GLP-1 receptors but are longer acting than exenatide. Studies conducted in mice treated with a chemical that attacks dopamine-producing brain cells suggests that these newer drugs are better able to prevent damage than exenatide.

There is currently a phase 2 clinical trial of liraglutide for Parkinson’s ongoing at Cedars-Sinai Medical Center in the US, and a phase 2 clinical trial of lixisenatide is underway in France. The latter is set to be the largest study of a diabetes drug for Parkinson’s to be conducted to date, involving 158 people.

More repurposed drugs in trials for Parkinson’s

But it’s not all about diabetes drug, there are currently trials taking place world-wide looking at the potential of repurposing drugs from a wide range of conditions for Parkinson’s.

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Cholesterol-lowering drugs: statins

Statins are a type of drug commonly used to decrease “bad” cholesterol levels in the blood. Often prescribed to people at risk of cardiovascular disease, statins improve the blood flow and restore the elasticity of the arteries.

Lab studies in cells and animal models of Parkinson’s have suggested that, in addition to their cholesterol-lowering properties, statins may also have a range of activities which could help protect brain cells in Parkinson’s. These include:

  • reducing inflammation
  • reducing oxidative stress
  • reducing the formation of sticky bundles of alpha-synuclein
  • increasing the production of neurotrophic factors

In addition, large scale studies in people have suggested that statins may help to reduce risk of developing Parkinson’s.

As a result, there is now a clinical trial of a type of statin underway in the UK. Simvastatin was selected because it is better able to enter the brain than most other statins.

This 2 year trial, supported by The Cure Parkinson’s Trust, involves 235 people with moderate Parkinson’s in 23 hospitals across the UK. Participants have been randomly allocated to one of two treatment groups:

  • one group has received simvastatin,
  • and the other has received a ‘dummy drug’ or placebo.

Information is being gathered from participants using a variety of questionnaires and practical tests during eight hospital visits over 2 years.

The trial is scheduled to finish in early 2020 and we’ll highlight the results as soon as they are available.

A liver drug: UDCA

Ursodeoxycholic acid, also known as ursodiol or UDCA, is an old drug that’s used to treat liver disease, reduce the formation of gall stones, and even reduce itching during pregnancy.

Parkinson’s UK-funded researchers at the University of Sheffield have discovered that UDCA may have another exciting ability. When they tested UDCA on skin cells from people with Parkinson’s they found that the drug had restorative effects on mitochondria — the tiny, energy-producing batteries that power all our cells — helping to boost energy production.

This is very encouraging because research suggests that mitochondrial failure is a key factor in the loss of brain cells in Parkinson’s.

Following their initial discovery, the research team confirmed the positive effects of UDCA on mitochondria in human dopamine-producing brain cells grown from skin cell samples from people with Parkinson’s, and also in animal models of the condition.

The team are now preparing to begin a small clinical trial of UDCA in people with Parkinson’s to assess safety and look for signs that the drug can have the same effects on mitochondria in people.

A cancer drug: nilotinib

Nilotinib is a treatment for chronic myelogenous leukemia (CML)— a cancer of the white blood cells.

In CML, a mutation causes a protein called Abl to join with another protein called Bcr. The hybrid protein (Bcr-Abl) stimulates the excessive production of white blood cells, which causes all kinds of problems. Nilotinib finds and binds to Bcr-Abl, switching it off and stopping white blood cell production.

So why might nilotinib be helpful for people with Parkinson’s?

Recent studies suggest that a closely related protein called c-Abl may play a role in the accumulation of toxic alpha-synuclein, and impair the cell’s ability to process and remove waste — both problems are thought to contribute to the loss of brain cells.

So, drugs that can find and bind c-Abl (like nilotinib) may help to protect struggling brain cells and have the potential to slow Parkinson’s.

In 2015, results of a small phase 1 trial in 12 people with Parkinson’s, who took nilotinib over a period of 24 weeks, suggested improvements in memory, movement and non-motor symptoms.

A phase 2 clinical trial of nilotinib in Parkinson’s — NILO-PD — is now underway in the US. The study, funded by the Michael J Fox Foundation, will recruit 75 people and aims to better understand the safety of taking nilotinib in the long-term for Parkinson’s. It will also further explore nilotinib’s potential to treat symptoms and slow, or stop, progression.

An iron-removal drug: deferiprone

Another problem in Parkinson’s is iron overload. It’s not clear why, but studies have shown that dopamine-producing brain cells tend to contain much higher than normal amounts of iron.

Iron is essential, but too much can be toxic and contribute to damaging processes like oxidative stress.

Deferiprone is a drug that is already used by people with blood disorders to help them remove excess iron, and it is able to get into the brain.

Promising results in animal models led to two small trials:

Both trials suggest that the drug is generally safe and well-tolerated, and brain scans indicated that it may reduce iron levels in the brain. More importantly there were promising signs of improvement in symptoms.

These encouraging findings led to a major EU-funded clinical trial in over 300 people across 8 European countries (including hospitals in the UK). The trial is recruiting people recently diagnosed with Parkinson’s who are not yet taking medication for the condition. The researchers hope to show that treatment with deferiprone can slow the progression of Parkinson’s compared to placebo treatment.

A blood pressure medication: isradipine

Isradipine is a calcium channel blocker currently prescribed to treat high blood pressure. It prevents calcium from entering cells of the heart and blood vessel walls, helping them to relax, which results in lower blood pressure.

Interest in isradipine for Parkinson’s came when data from large studies suggested that people who took the drug for high blood pressure were less likely to develop Parkinson’s.

Scientists think that isradipine may be protective because it blocks calcium channels on the surface of the dopamine-producing brain cells. Normally these cells are continuously flooded with calcium, which is believed to contribute to damaging oxidative stress and ultimately cell death.

Following promising results in animal models and small scale clinical trials, in 2014, researchers in the US received an eye-watering $23 million to conduct a phase 3 trial of isradipine in 336 people with Parkinson’s. The trial is still underway but is expected to finish in 2019.

A cough medicine: ambroxol

In 2004, doctors noticed that people with a rare genetic disorder called Gaucher’s disease often had relatives with Parkinson’s.

Gaucher’s disease is caused by inheriting two faulty copies of a gene called GBA, one from each parent. Research has now shown that people who carry just one faulty copy of GBA are at higher risk of Parkinson’s.

The GBA gene makes a protein, called glucocerebrosidase (or GCase), that helps to regulate levels of alpha-synuclein — a protein that is known to accumulate inside the cells affected in Parkinson’s. When GCase doesn’t work properly alpha-synuclein levels increase. So, finding ways to restore or increase GCase may provide a route to protecting brain cells affected in Parkinson’s.

Ambroxol — a drug that breaks up phlegm and is used to treat coughs and sore throats — has been shown to increase the activity of GCase in lab studies.

Researchers at University College London are conducting a small clinical trial in 20 people with Parkinson’s — 10 with and 10 without GBA mutations — to confirm the safety of ambroxol. The study will assess the drugs ability to get into the brain, and investigate if it can lower alpha-synuclein levels.

There is also a second phase 2 trial of ambroxol underway in Canada, which will involve 75 people with Parkinson’s dementia, to see whether it can improve memory and thinking problems.

A dementia drug: rivastigmine

Rivastigmine (sold under the trade name Exelon) is used for the treatment of mild to moderate dementia. It works by preventing the breakdown of a chemical transmitter in the brain, called acetylcholine, that is important for memory and concentration.

Results from a phase 2 clinical trial funded by Parkinson’s UK, published in 2016, showed that rivastigmine may help to improve walking and prevent falls in people with the condition.

The researchers believe that boosting acetylcholine in the brain helps people pay more attention to their walking and balance, which means they are less likely to trip or fall.

Rivastigmine will now be tested in a larger phase 3 trial funded by the National Institutes of Health Research (NIHR). The study will start in early 2019 and will recruit 600 people with Parkinson’s across 26 UK hospitals.

More to come from repurposing

The hunt is still very much on for more potentially repurposable drugs for Parkinson’s.

One particularly promising new prospect is the asthma drug salbutamol, which scientists discovered may be able to reduce levels of the alpha-synuclein protein in 2017.

And scientists are hard at work sifting through the thousands of currently available drugs to find more. You can read more about the different approaches to spotting these needles in the haystack in our previous blogs:

Should this search prove fruitful, it is likely to result in more clinical trials in the future. If you are interested in what research opportunities there are in your area or would be interested in taking part in research at home, you can now search our website for local studies.

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Parkinson’s UK

Get the latest research news, discover more about…

Claire Bale

Written by

Head of Research Communications and Engagement, Parkinson’s UK

Parkinson’s UK

Get the latest research news, discover more about Parkinson’s and read about how others are getting involved. For information and support, visit

Claire Bale

Written by

Head of Research Communications and Engagement, Parkinson’s UK

Parkinson’s UK

Get the latest research news, discover more about Parkinson’s and read about how others are getting involved. For information and support, visit

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