Today (28th February) is Rare Diseases Awareness Day. This is such an important day but has an almost impossible ask – there are more than 6,000 rare diseases that we know of, so if we covered one rare disease every day, it would take more than 16 years! This isn’t even considering those we don’t know about yet. What I can do in this blog post is give you some insight into rare diseases as a subset of medical research and how current advances in scientific technologies can help develop treatments for a lot of them.
What is a rare disease?
In the UK, a disease is considered rare if less than 1 in 2,000 people in the population have it. More than 3.5 million people in the UK alone live with a rare disease. Some of these you may have heard of, such as cystic fibrosis, sickle cell anaemia and Duchenne muscular dystrophy (DMD), and others maybe not, such as immune thrombocytopenic purpura (ITP), Addison’s disease and moyamoya.
Why are rare diseases so difficult to treat?
The answer is in their rarity. For a treatment to get approved for prescribing in the UK, extensive clinical trials are usually needed (I’ll come back to the usually in a moment). Because of natural variability in the way people respond to treatments, for clinical trials to be successful, they often require large numbers of people to sign up. When only a handful of people suffer from a rare disease, it is difficult to find people with the condition, let alone enrol them in a clinical trial. Getting treatments approved is also an expensive business – it is estimated that the typical cost to bring a drug to market is $1.3 billion (nearly £1 billion); therefore, it is difficult to justify that cost for a condition that not many people suffer from. To add to the difficulty, any treatments that do make it through are often very expensive to cover the development cost.
Is an extensive clinical trial always needed?
(I said I would come back to this) Usually extensive clinical trials are required for a new medication to be prescribed in the UK; however, for very serious diseases for which no treatment, or no satisfactory treatment, is available, a medicine can be designated an orphan drug. This is a drug that would not be profitable to produce without government assistance. This designation allows approval of these drugs for the treatment of rare diseases after clinical trials with fewer participants than would usually be acceptable for non-orphan drugs.
What alternatives are there to new drug development for rare diseases?
A good way to find treatments for rare diseases is by repurposing medicines that are already approved for other conditions. The beauty of finding new uses for old drugs is that the clinical trials showing the safety of the drug in humans have already been carried out, so rather than spending limited funds on large clinical trials of new medicines, the company producing the drug just needs to show that the medicine is effective for the rare disease and has similar safety. One of the great things about repurposing medicines is that, in order to do it, you need to have an understanding of how the rare disease works so that you can test treatments that are most likely to be effective. This means that there is more and more research into the underlying causes of rare diseases, not only helping to find treatments but also helping people who have the disease understand their condition and find ways to manage it.
What about gene therapy?
Gene therapy is a blog post in its own right – I have a lot to say about this topic having covered gene therapy for a rare disease (cystic fibrosis) for my PhD research – so watch this space! In the context of rare diseases, gene therapy has the potential to be the holy grail for those diseases with a known genetic cause. In a nutshell, part of gene medicine is about finding a way of getting the correct version of a gene to the right place in someone who has a faulty version of the gene. The gene is carried by something we call a vector, this could be fat particles, a virus, or even gold nanoparticles. Gene medicine could be a lifeline for some people with rare diseases that have a genetic cause. For example, if a company has developed a gene medicine for cystic fibrosis where the vector targets the lungs and it has been approved, then they could adapt this drug by using the same vector to carry a different gene into the lungs. This could be a gene to treat a different genetic rare disease affecting the lungs, like alpha-1 antitrypsin deficiency. The approval process for the drug would be simpler as the main component of the drug (the vector) has already been approved for use in the same organ.
What is happening in the UK?
The UK government have released their plans for the UK Rare Diseases Framework, which will focus on increasing awareness of rare conditions, and coordinating care and access to therapies for people who suffer from them. This will be a great foundation for improving the lives of people with rare diseases in the UK.
For more information about rare diseases, the UK Rare Disease Framework, and to help fund research into treatments, visit the Rare Disease UK website: https://www.raredisease.org.uk/rdd2022/light-on-rare/. For an insight into what it is like to have a rare disease, check out the stories shared by people in the rare repository, or if you suffer from a rare condition yourself you can also share your story: https://www.raredisease.org.uk/rdd2022/rare-repository/.
Another useful resource is orphanet, which is an online portal for rare diseases and orphan drugs: https://www.orpha.net/consor/cgi-bin/index.php?lng=EN.