You might think that rare diseases hardly affect anyone. But if you take them all together, one in twenty people worldwide suffers from a disease that falls under this term. On the most unusual day of the year, 29 February, numerous international initiatives are dedicated to raising awareness about rare diseases. As in most years, Rare Disease Day 2023 is observed on 28 February as a substitute. I took this opportunity to explore the topic of rare diseases.
Rare diseases at a glance: 5 questions and answers
What is a rare disease?
A rare disease affects comparatively few people, but is particularly dangerous for them. Different countries apply different standards: In the USA, a disease is considered ‘rare’ if it occurs in no more than 200,000 inhabitants in total. In the European Union, this upper limit is 1 in 2,000 inhabitants.
Over 70 percent of the known rare diseases are genetic. In more than two thirds of those affected, the first symptoms of the disease appear in childhood. But tumour diseases as well as the consequences of infections or allergies can also fall under the definition of rare disease. Worldwide, an estimated 300 million people live with a rare disease — this corresponds to 5 percent of the world’s population. So rare diseases are not that rare after all!
How many rare diseases are there?
We do not know the exact number of rare diseases. In general, experts counted 7,000 to 8,000 known rare diseases until now. In 2022, the US non-profit organisation RARE-X identified a total of 10,867 rare diseases.
This significant difference is partly a result of different definitions and standards — each country counts slightly differently. At the same time, we are getting better at understanding how individual diseases develop and what makes them tick. For example, we may learn that a group of patients is not suffering from one and the same disease at all, but from two different, very similar diseases. Other patients are now receiving a diagnosis for the first time ever — thanks to advances in medical research.
Why are there so few treatments for rare diseases?
Developing a drug and bringing it to market costs a lot of money. At the same time, the patient groups of individual rare diseases are so small that only few people would benefit from a drug. Therefore, it is often not worthwhile for the pharmaceutical industry to research possible treatments of rare diseases.
Even when a drug is developed and tested, however, there is often little patient data available: after all, only a handful of cases are known of some of these diseases. This complicates research and the approval process for these ‘orphan drugs’.
The result: for about 95 percent of the known rare diseases, there is no approved therapy — and progress in research is very slow.
Who funds research into rare diseases?
In the EU, the Orphan Drug Regulation states that every patient has the same right to medical treatment — no matter how common their condition. This is why research into rare diseases and appropriate treatment options is regularly funded.
Between 2007 and 2020, more than 440 international research projects on rare diseases were supported by the EU: More than 2.4 billion euros were invested in the development of diagnostic and treatment approaches.
Numerous initiatives such as Rare Disease Moonshot also link public and private research and work to develop appropriate therapies even faster and more efficiently.
What progress are we making in rare disease research and treatment?
From 2000 to 2021, more than 200 new orphan drugs were approved by the European Medicines Agency (EMA). This shows that progress is definitely being made. After all, up to 6.3 million patients benefit from these new treatment options.
Experts expect up to 28 new drugs for rare diseases on the European market by 2023.
Current developments: 3 research successes in rare diseases
Stem cell therapy for cerebral adrenoleukodystrophy (CALD)
Like the majority of rare diseases, adrenoleukodystrophy is caused by a genetic mutation — in this case a defect of the ABCD1 gene. This metabolic disease is hereditary, often occurs in childhood and usually only affects boys. Very long chain fatty acids accumulate in various organs and especially in the brain. The affected children suffer from severe neurological impairments, which are usually fatal. The childhood cerebral form of the disease progresses particularly quickly.
In autumn 2022, a personalised gene therapy received approval from the Food and Drug Administration (FDA) in the USA. The drug Skysona is individually produced with the help of the patient’s own stem cells and administered by infusion. The faulty ABCD1 gene is replaced in this way, and after chemotherapy the modified stem cells can start working in the patient’s body. Skysona does not repair damage that has already occurred, but initial studies show that the disease progresses much more slowly in the children treated.
Drug for African trypanosomiasis
The pathogen that causes the tropical disease trypanosomiasis, also known as sleeping sickness, is transmitted by the tsetse fly. We can only estimate how many people are affected — but it is considered a rare disease. After the initial infection, patients show typical flu symptoms. Later, they suffer from cramps and neurological problems until they become drowsy. If left untreated, trypanosomiasis is fatal.
Until now, several therapy options have been available. However, patients had to be treated in hospitals over a long time. In practice, therefore, only a few affected people benefited from this option. In November 2022, the promising results of a study were published: with the drug acoziborole, African trypanosomiasis could be successfully treated in more than 95 percent of cases. Particularly interesting: In contrast to previous therapies, only a single dose in tablet form is necessary here.
Stem cell therapy for Pearson syndrome and Kearns–Sayre syndrome
Nothing works in the human body without mitochondria, which is why they are often called the ‘powerhouses of the cell’. The mitochondrial DNA (mtDNA) they contain is passed on from generation to generation — always from mother to child. If something goes wrong and the copy of the mtDNA remains incomplete, diseases such as Pearson syndrome and Kearns–Sayre syndrome can develop. The affected child then suffers from various symptoms and secondary diseases that can be fatal.
Significant advances in the treatment of this disease were first reported in late 2022. An Israeli team succeeded in improving the general condition of six children with the disease. To do this, the doctors took stem cells from the bone marrow of each child and enriched them with healthy mtDNA from the blood cells of the respective mother. The modified stem cells were then infused into the organism of the sick child. There, they successfully replaced some of the patient’s own stem cells, which were equipped with a defective mtDNA.
Raising awareness about a global issue: Rare Disease Day 2023
The European Organisation for Rare Diseases (EURORDIS) brings together almost 1,000 organisations and initiatives focused on the issue of rare diseases. Since 2008, EURORDIS has coordinated Rare Disease Day on 28 or 29 February and carries out important awareness-raising work throughout the year.
In Germany, the Alliance of Chronic Rare Diseases (ACHSE) gives a voice to people with rare diseases and offers support to self-help organisations with its extensive network.
Orphanet, founded in France and funded by the European Commission, provides information on rare diseases, their respective research and previous and ongoing projects.
In the USA, the National Organization for Rare Disorders (NORD) promotes research into treatment options and provides information on rare diseases and orphan drugs.