Therapeutic development

Therapeutic development generally takes place in three successive stages: basic, preclinical and clinical research. Each of these stages can take years to complete, and new therapies mostly never make it to market. Here we describe what happens in each stage of research into muscle-wasting conditions, and how each stage contributes towards the development of a potential new therapy.


Basic research usually takes place in the laboratory. It focuses primarily on understanding the cause of a condition and how this leads to muscle weakness and wasting. This involves studying cells – which could be from patient samples – and animal models, in order to answer a range of research questions. For example, key questions for many muscle-wasting conditions could be:

  • which gene is mutated?
  • what is the specific mutation?
  • how does this affect the protein that is made from the gene?
  • how does this then affect muscle function?

Once they have the answers to these questions, researchers can start to investigate possible ways to address the underlying cause, and tackle the muscle wasting and other symptoms. This is when research starts to become ‘translational’: researchers use findings from the basic laboratory studies to develop targeted, potential treatments. Promising therapeutic approaches may then advance to preclinical studies.

It is important to remember that basic research does not end with the identification of the cause of a condition. There is still a lot we don’t understand about muscle-wasting conditions and it is often only through basic laboratory studies that we can answer these questions.

Even when there are approved treatments available, basic research is a crucial step towards informing the next generation of even better treatments. For example, although there are now exon-skipping drugs in clinical trials for Duchenne muscular dystrophy, we still don’t know which parts of the dystrophin protein are essential for its function in different parts of the body. Basic laboratory research is the only way to gain this knowledge, and it will help to improve future exon-skipping drugs.


Preclinical research involves all the experiments to assess the safety and efficacy of a treatment before testing it in human trials. Initially, researchers test the treatment in cells isolated from individuals with the specific condition. This determines whether the treatment works as expected and, if so, how effective it is and whether or not it is toxic to the cells.

As isolated muscle cells do not represent the complex three-dimensional structure of a working muscle, the next stage is to test the treatment in a condition-specific animal model, typically mice. To ensure the best chance of success for a new drug or treatment, it is important to have properly designed animal studies with results that are reproducible.

Animal models allow scientists to further assess a potential treatment and answer crucial questions. These could include:

  • what is the best administration method?
  • is the drug or treatment able to reach muscle cells?
  • is it toxic?
  • what is the best concentration?
  • how often should it be administered?
  • does it improve muscle function?

Finally, before a treatment can progress into early phase clinical trials, researchers need to test its toxicity thoroughly. These experiments – also known as toxicology studies – identify any harmful side-effects, as well as the safest dosing range (based on animal studies) to test the treatment in clinical trials.

Researchers usually carry out toxicology studies in healthy animals that do not have the condition the researchers are trying to treat. Mice are not always suitable for toxicology testing, as they often do not show any harmful side-effects. Larger animals, such as rats, dogs and monkeys, are usually more suitable.


Clinical studies cover any form of research involving people. This includes observational studies, to understand more about a muscle-wasting condition and how it progresses (its natural history), and clinical trials, to assess the safety and effectiveness of specific interventions. These interventions could be medical products e.g. drugs, devices, vaccinations; medical procedures e.g. a type of surgery; or changes to a person’s lifestyle e.g. an exercise regime.

As with any experiment, researchers design clinical trials to answer specific research questions. After reviewing what is already known about the treatment, from preclinical studies or previous trials, researchers will develop a specific plan or protocol, outlining:

  • who can take part (eligibility criteria – often called inclusion and exclusion criteria)
  • how many people are needed at each stage to ensure robust data collection
  • how long the study will last
  • whether or not there will be a control group (to limit bias)
  • how the treatment will be administered and at what dosage
  • what will be measured (outcome measures) and when
  • how the data will be reviewed and analysed.

Clinical trials typically follow a series of stages, or phases:

Phase 1 – aims to assess the safety of a treatment. Phase 1 trials involve a small number of people, who are often healthy volunteers. However, in the case of genetic therapies, these trials are carried out in people with the condition. The researchers adjust dosing schemes based on preclinical data from animals, to find out how much of a treatment the body can tolerate and what its potential side-effects are.

Phase 2 – aims to assess the safety and effectiveness of a treatment. This may be the first time of testing it in people who have the condition the treatment is intending to treat. Researchers may divide participants into groups – one of which will receive the optimal dose, the other of which will receive a different dose or a placebo (an inactive substance designed to resemble the treatment being tested).

Phase 3 – often referred to as the ‘confirmatory’ phase, phase 3 aims to prove the effectiveness of a treatment in people with the condition. Researchers will usually compare the new treatment against the current standard treatment (if one exists). These trials not only take much longer than phase 1 or 2 trials, but also are also much larger, often involving people from multiple centres across the world.

Phase 4 – also known as ‘post-marketing surveillance’, these studies take place after the regulatory authorities have approved the treatment. These studies give information about the long-term risks and benefits of the treatment in a much larger patient population, many of whom may also be receiving treatment for other conditions. This helps to identify the risks and benefits in a ‘real world’ situation.

Some clinical trials may fall in two of these phases. For example, you may see phase 1/2 trials, which aim to identify the highest safe dose, as well as how well that dose works.

In order for clinical studies to take place, certain types of clinical support and infrastructure must be available. These include clinical trial co-ordinators, who help with the setting up and running of clinical studies at a particular centre. They are responsible for ensuring that the research takes place within regulatory guidelines as well as the specifications outlined in the trial protocol. Muscular Dystrophy UK currently supports three clinical trial co-ordinators at the muscle centres in Newcastle, London and Liverpool.

Patient registries also help to support clinical studies, in particular those for rare diseases, such as muscle-wasting conditions. This is because the patient population is small and widely dispersed across the world, which can make recruitment for clinical studies challenging.

Registries are databases that contain information about individuals living with a particular condition. With permission, researchers and companies can view this information and recruit eligible patients for trials. Muscular Dystrophy UK currently supports four patient registries: myotubular and centronuclear myopathies, collagen VI-related myopathies, facioscapulohumeral muscular dystrophy and myotonic dystrophy.

Even if a new treatment gets through the lengthy process of clinical trials, there is still the final hurdle of making it available for patients living in the UK. It must be approved by the European Medicines Agency (EMA), and then by the relevant health technology assessment (HTA) bodies in the UK. While the EMA evaluates the risks and benefits of a new treatment, HTA bodies will assess its cost-effectiveness.

Through our FastTrack campaign, we are working hard to ensure that people living with muscle-wasting conditions in the UK get access to promising treatments, and as quickly as possible.

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