In Limbo

Author: Nina Himmer |
Photo: Science Photo
Rare diseases are mysterious. Their causes are found in the genes. Doctors have no effective way to treat most of these diseases. Those afflicted and their families are often left to fend for themselves

The letter arrives on a Thursday in May. Sandra Richard pulls it out of the mailbox and barely makes it back to her apartment. Her heart is pounding, her throat constricted. She has waited three months for this letter, and now she wishes the pale green envelope had never reached her. The letter inside the envelope contains a number, and that number will decide her future. This number indicates the recurrence of a gene responsible for the rare nervous disorder Huntington’s disease (also known as Huntington’s chorea). This disease destroys brain cells and eats away at the areas of the brain responsible for speech, motor function and personality. The process is fatal – there is no effective treatment. Sandra Richard’s grandfather died of it, and her father also had it. It was only with his diagnosis that the family first learned of this hereditary disease at all.

Is this disease lurking in Sandra’s genes, too? The risk of this is 50 per cent; a genetic test provides clarity. A few drops of blood are enough to detect the presence of Huntington’s disease. The test is quick – that’s not why Sandra had to wait three months. The three-month waiting period is mandated by law, so that those affected can have time to decide whether they want to know for sure.

It takes a while for Sandra to decipher the medical jargon in the letter, but once she has done so, she learns that she has the disease. Up to 30 gene recurrences are normal; in Sandra’s case, there are 39. Too many. Still, she will probably get the disease only in old age. When exactly, though? Nobody can say.

Both rare an common

In Germany, approximately 8,000 people have Huntington’s disease. But the grace period that the disease grants these people is rather uncommon. In 80 per cent of cases, rare diseases are genetically determined. Many people suffer from the consequences of a genetic defect starting right at birth, and the families of people who have rare diseases bear a heavy burden as well. A disease is considered rare in Europe if no more than five out of 10,000 people are affected. That doesn’t sound like much, but in Germany alone about four million people suffer from one of the 8,000 rare diseases known to date. “It is a large but very mixed group,” says Professor Heiko Krude, director of the Centre for Rare Diseases at the Charité Hospital in Berlin. Because every disease is different. In cystic fibrosis, for example, the organs become blocked by thick mucus. In the case of “butterfly disease”, epidermolysis bullosa, the skin layers detach from each other. An aniridia is when the iris of the eye does not form properly. Some diagnoses are more common; others are only made once or twice worldwide. “Time and again we also see patients with completely unclear symptoms,” reports Krude.

As different as the diseases and their symptoms are, the problems of those affected are very similar. “In almost every case, there is too little information, too few experts and too few medications,” says Christine Mundlos of the Alliance for Chronic Rare Diseases (German acronym: ACHSE), which represents the interests of those affected. “Everything in our health system is geared towards common diseases, which is why people with rare diseases often simply fall through the cracks,” says Mundlos, who is also a physician. It often takes years and countless visits to doctors before it is even clear what a patient is suffering from. If the disease is finally given a name, the odyssey continues. “It is difficult to obtain information, which is often available only in English and in special databases. The search for a medical expert is also a challenge, because they are just as rare as some pathologies,” says Mundlos. The biggest problem, however, is the lack of medications and therapies: for over 90 per cent of rare diseases there is no effective treatment. For this reason, the patients are referred to as “medical orphans”. Many of them are still on their own: “In Germany, there is a lack of suitable care structures for these patients – everything is left too much to chance,” says Mundlos.

Sandra Richard also felt left alone after the test. First she sank into anger and grief, then she threw herself into work. “I didn’t want to think anymore, I just wanted to work.” Four years after the test, she meets Paul, who is now her husband, and her life becomes positive again. “He’s my anchor in life, he has given me a new perspective, and he’ll calm me down if I get too worked up about the disease.” She becomes pregnant – which is good news, because after an inflammation of her fallopian tubes the doctors had actually ruled out pregnancy. Sandra, however, breaks down. For a long time, all she thinks about is, “What if my child is sick too?” Paul calms her down: “We can do this,” he says. “This is probably meant to be.”

Who should pay for it

Rare diseases are complex and chronic, requiring state-of-the-art diagnostics and lengthy, complicated treatments. In short: they are expensive. “Patients typically need several specialists, because the disease has a variety of effects,” says Krude. A pilot project is underway at the Charité, in which doctors from different disciplines discuss patient cases at a “case conference”. It’s a service that, in accordance with the current standards, is not billable.

If it were up to the National Action League for People with Rare Diseases (German acronym: NAMSE), things would be different. Launched in 2013, NAMSE is financially supported by Germany’s Federal Ministry of Health, and it aims to bring patients and doctors together, pool information, establish specialised centres and promote research. Under normal conditions, it is not very attractive for companies to develop drugs for rare diseases – the markets are small, and thus it’s difficult to recover expenses. Medications for common diseases such as asthma, cancer or diabetes are more lucrative. For a long time, very little was known about rare diseases, most of which are hereditary. “Until the human genome was decoded, we could only grope about in the dark,” says Siegfried Throm of Germany’s Association of Research-Based Pharmaceutical Companies (VfA).

Around the year 2000 there were two breakthroughs: In the United States, researchers decoded the human genome. Almost at the same time, the EU’s drug authority decided to promote the development of drugs for rare diseases. “Since then, the approval of so-called orphan drugs has increased, levelling off at around 14 approvals per year for Europe,” says Throm. Although the active ingredients account for around a quarter of newly approved drugs, their impact on company sales remains small: in 2017, rare diseases accounted for only 3.7 per cent of drug expenditures by health insurance companies in Germany.

„Insane with fear“

The small market is not the only problem. “There are only a few experts, and they are scattered around the world. In addition, there is a lack of structured information and standardised databases – and it’s hard to find enough patients,” explains Throm. Stem cell and gene therapies, for which many patients have high hopes, could be promising. Bettina Eckart also often wonders whether such a therapy could prevent the onset of her disease. Experts, however, are trying to limit expectations. “Progress over the last ten years has been positive,” says Heiko Krude of the Charité Hospital. “But we simply still know too little about the exact interrelations.”

Five years after the start of NAMSE and almost 20 years after the start of EU funding, the results are mixed. “A lot has changed, but the momentum is gone,” says ACHSE spokeswoman Christine Mundlos. The financing from the Federal Ministry of Health will expire this year, and it is still unclear how NAMSE will continue. There would still be a lot of work to do: certification of the 27 centres according to uniform standards, additional training of doctors, faster diagnosis and treatment for patients, more money for research. “We must keep NAMSE running and prevent a standstill,” says Mundlos, “otherwise people with rare diseases will continue to be medical orphans.”

Sandra Richard hopes things will turn out differently. Not just for her, but also for her daughter, who is now six years old. “Since Leni was born, I have no doubt that giving her life was the right thing to do,” Sandra says. Nevertheless, some days the fear almost drives her insane. It is still completely unclear whether Leni has the disease. A test is only possible – and allowed – from the age of 18; the people at risk decide for themselves whether they want to take the test. So it will be some time before that happens for Leni. “Maybe by then the world will look a little more hopeful for us rare cases,” says Sandra Richard. “And until then, we will simply live in the here and now as best we can.”

Imagine that all the characters and spaces in this article correspond to the population of Germany. Then all of the blue characters correspond to the number of people suffering from Huntington’s disease in Germany (8,000). The red characters represent people in Germany suffering from a rare disease (about four million). Red characters that are underlined indicate people with rare diseases for which there are no promising treatment methods.