Drug repurposing – harnessing the positive side effects of ‘old school’ drugs

Drug repurposing – harnessing the positive side effects of ‘old school’ drugs

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Is it possible that a drug that treats congestive heart failure could improve respiration in people with MND? Or that a drug used to treat cancer could reduce motor neuron inflammation and possibly slow progression of the disease? In this blog we take a look at drug repurposing – using a drug developed to treat a particular disease to treat another that is unrelated – what it is, and what it might mean for people living with MND.

Reduce, re-use, recycle – repurposing drugs for new functions

Repurposing drugs is not a new idea. Many drugs have found a new function – thalidomide, given to pregnant women in the late 1950’s/early 1960’s when it was withdrawn for causing catastrophic birth defects, is now used as a treatment for leprosy and a rare type of cancer. Another, tamoxifen, originally developed to treat breast cancer is now used in the treatment of bipolar disorder.

Drug repurposing is a practical solution to overcome costly and lengthy clinical trials. Developing a new drug – from concept to clinic – is a very slow and very expensive process, potentially costing tens of millions of pounds and taking more than ten years. Drugs that have already undergone this process are increasingly being investigated as potential treatments for other diseases, including MND, as they have already been found to be safe for use in people, therefore ‘cutting out’ the early part of the clinical trial process. You can read more about how clinical trials work in our information sheet.

So how can a drug that treats one disease work for another?

Our bodies are made up of proteins – thousands of them – and each type of protein can reside in different parts of the body and have a variety of jobs. Proteins also have a role to play in illness and drugs work by interfering with the way these proteins function in our cells. Obviously, once a drug enters the body, we have little control over where it goes so, although it might be designed to treat, for example, proteins in kidney cells it also travels to other places where the target protein is found. These ‘off-target’ effects are what cause the side effects of drugs, because the normal function of the cell is being disrupted, and this can be harmful. Sometimes, though, this disruption can have positive effects and it is these beneficial outcomes that drug repurposing is attempting to exploit. A well-publicised example of this is Viagra, which was designed to target heart cells but had a surprising side effect, for which it has been repurposed.

However, we can’t take an approved drug and give it to people with a different condition just because we think it might work for them. Pre-clinical tests and clinical trials are still needed. The good news is that these may be fewer, less time-consuming, and therefore considerably cheaper. Neurologists themselves are now leading trials using approved drugs as potential treatments for MND, as is the case in the MIROCALS trial for example (more about that later). The savings in time and money come because the compound has already gone through the process of research and development, and a considerable amount of safety testing, to gain approval for its original purpose. That said, a safe dose still needs to be established in the new disease target, some degree of effectiveness seen, and we must fully understand the benefits and risks before the drug can be made available as a new treatment.

What does this mean for people with MND?

Because there is currently only one drug available in the UK to treat MND, riluzole, it is vital that new treatments are identified as soon as possible. Repurposing drugs is an opportunity to get potential new treatments through the clinical trials process faster and into clinics. Although researchers have yet to find an existing drug that effectively treats MND, there are many trials taking place around the world and we are going to look at some of these in more detail.

GET INVOLVED – trials taking place in the UK that are using repurposed drugs

An important note PLEASE REMEMBER that all clinical trials have strict inclusion and exclusion criteria and it is therefore possible that you may not be eligible to take part. You can talk to your neurologist to decide which clinical trial, if any, would be best for you.

MIROCALS – IL-2: from treating cancer to protecting motor neurons

This trial is testing Interleukin-2 (IL-2), a drug which is already used to treat some forms of cancer. IL-2 is naturally produced by the body. Its main role is to promote the production of Regulatory T cells (or Tregs) – part of the immune system thought to play a role in protecting nerve cells against damage. The drug IL-2 can increase the levels of Tregs in the blood so might be able to protect motor neurons in MND, slowing progression of the disease. Studies have already identified the lowest dose of IL-2 that still triggers an increase in Tregs without any serious side effects.

The purpose of this Phase 2 trial is to evaluate the safety and effectiveness of IL-2 and to confirm that modifying immune responses through increasing Tregs will slow progression of MND. The study will recruit 216 participants and results are expected Autumn 2021.

You can find out more about the MIROCALS trial in our information sheet and on the website.

Levosimendan – a heart medicine that could preserve respiratory function

Levosimendan is used to treat congestive heart failure by enhancing myocardial contractility – the innate ability of the heart muscle to contract without us having to do anything to help – and causes the widening of blood vessels increasing blood flow. As people with MND experience difficulty breathing due to their muscles becoming weaker, this Phase 3 trial aims to evaluate whether prolonged treatment with levosimendan can preserve respiratory function in 450 people with MND. The trial is expected to end in Autumn 2020. Find out more on

TUDCA – a treatment for liver disease that could protect motor neurons from programmed cell death

TUDCA is a water-soluble bile salt used to treat cholestasis, a liver disease in which bile acid backs up in an unhealthy liver causing damage to the cells by destroying the membranes and signalling cell death. TUDCA also appears to reduce stress to the endoplasmic reticulum (ER), an organelle in the cell that serves as a highway from the nucleus to the cytoplasm and aids in folding proteins. Through reducing ER stress, TUDCA may be protective against neurological damage.

The purpose of this Phase 3 trial is to evaluate the safety and efficacy of TUDCA as an add-on treatment to riluzole, measured by improvement in ALSFRS-R scores, in 440 people with MND and is expected to finish in Summer 2022. The ALSFRS-R is used to evaluate and monitor functional change in a person with MND over time. It consists of 12 questions that deal with aspects of the person’s daily life, each of which is scored by the person 4 to 0, with 4 being ‘normal’.

You can find out more about the TUDCA clinical trial on the TUDCA website and on

Drug repurposing trials for MND around the world

Perampanel – an antiepileptic that may prevent the toxic build-up of TDP-43

Perampanel works by decreasing abnormal electricity in the brain. In a mouse model of MND, it was found to prevent the death of motor neurons by stopping the toxic build-up of the protein TDP-43. Long-term treatment with perampanel also led to a visible improvement in motor function in treated mice.

The purpose of this Phase 2 trial is to evaluate the effect of perampanel on disease progression (measured by ALSFRS-R) in 60 people with sporadic MND and results are expected Winter 2022. You can read more about this trial on

Ranolazine – the angina drug that may be neuroprotective

Used to treat angina (chest pain), ranolazine works by inhibiting an accumulation of sodium and calcium ions in cells, although exactly how this treats angina is not fully understood. Calcium ions have an important role in hyperexcitability, when the neurons ‘fire’ more than they would normally, causing fasciculations (muscle twitches), one of the early symptoms of MND. Ranolazine may be neuroprotective by reducing neuronal hyperexcitability, therefore slowing disease progression and reducing cramp frequency.

The Phase 2 trial will evaluate the safety and effectiveness of ranolazine in 20 people with MND and is expected to finish Summer 2019. Find out more at

Pimozide – an antipsychotic that could improve muscle function

Pimozide is used in the treatment of schizophrenia and to reduce uncontrolled muscle tics seen in Tourette syndrome. It works by decreasing the activity of dopamine, a neurotransmitter that helps send messages between cells in the brain. In people with MND, damage to motor neurons causes a breakdown in communication between neurons and muscles at the neuromuscular junction (NMJ). Pimozide has been demonstrated to enhance communication at the NMJ in mice and fish with the goal of improving muscle function.

This Phase 2 trial will look at whether pimozide may help to slow the progression of MND in 100 people with the disease. The trial is expected to finish at the end of 2019 and you can read more on

Rapamycin – the anti-rejection drug that may prevent neurodegeneration

Used to prevent rejection of transplanted organs, rapamycin works by weakening the body’s own immune system to help it accept the new organ. Two potential influences in the development of MND are the neuron’s inability to remove the build-up of proteins in the cytoplasm and an unbalanced function of the immune system which causes it to damage motor neurons (neurotoxicity) rather than protect them (neuroprotection). These two mechanisms represent important therapeutic targets. In models of neurodegeneration it has been shown that rapamycin can suppress inflammatory neurotoxic responses brought about by T cells (T cells are part of the immune system and usually protect nerve cells against damage), and help breakdown protein that has accumulated in the cytoplasm.

The aim of this Phase 2 trial, which will involve 63 people with MND, is to obtain predictive information for a larger study. It is expected to finish in Autumn 2019. You can find out more at

Not all of these trials will necessarily produce results that will lead to a new treatment for MND, but we are all hoping for positive results from any of the above trials. There are, however, many more trials underway and it is encouraging that drugs proven to treat so many other conditions may be potential treatments for MND.

The search continues

Scientists, researchers and neurologists are working hard to identify more drugs from the thousands that are already available that may have the potential to deliver new and better treatments. The search continues to fill the desperate need for an effective treatment for MND and it is hoped that drug repurposing will achieve this much more quickly, easily and cheaply.


6 thoughts on “Drug repurposing – harnessing the positive side effects of ‘old school’ drugs

    1. Thank you for your kind comments. It is always good to know that the information we provide is of interest.
      Kind regards, Mandy

  1. BS. Drugs will be classified as off label. I guess drug companies are more concerned about erectile dysfunction than als. Greed! Please God let someone care about curing als. I think my son would be ok without the Viagra but would love to walk, talk, eat and breathe.

    1. Dear Carol

      Thank you for taking the time to read, and comment, on our blog article. Let me say how sorry I am to hear of your son’s diagnosis.

      Viagra was used as an example of a repurposed drug simply because it is one that most people have heard of. It is not being looked at as a potential treatment for ALS. I apologise if you found the reference inappropriate.

      It may be that some of the drugs currently being trialled for repurposing will never be recognised as treatments for ALS and will need to be prescribed as an off-label treatment. However, it is hoped that some, at least, will meet the criteria necessary to be licensed as a treatment for ALS in their own right and this will make them widely available.

      With regard to drug companies being more concerned about making money than finding a treatment for ALS – drug companies need to make profits to further their research. We are encouraged that there is so much interest in new treatments, be they from existing drugs or newly developed compounds. We all hope that a new therapy will become available soon, with a cure in the not too distant future.

      Research is also continuing to improve ways to help with symptoms that people living with ALS are coping with on a daily basis. These projects tend to be much shorter and produce results that are beneficial to people living with the disease now.

      If you have any more questions you can contact us directly on

      Kind regards

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