More people are impacted by rare diseases than by cancer and AIDS combined. With 400 million patients suffering from rare diseases worldwide, they seem not so rare after all. But a lack of education, infrastructure, and technologies makes the diagnosis of these diseases highly challenging. With over 25 years of experience in the rare disease space, Arndt Rolfs, founder and CEO of CENTOGENE, has built a global network to improve the diagnosis and treatment of rare diseases worldwide. To help raise the visibility of rare diseases, the company will be hosting a rare disease film festival in 2021.
“I don’t like the name ‘rare disease’,” says Rolfs. “It’s not a good idea because it gives many doctors the impression that they will never see a patient with a rare disease. And the burden for patients suffering from any form of a rare disease typically starts with a late diagnosis.”
One of the key problems is that many doctors lack education in the rare disease space, Rolfs explains further. They do not understand the workflow needed to identify rare diseases and diagnose patients, which causes a significant diagnostic delay in the majority of patients.
To date, it takes an average of seven years for a patient to receive an accurate rare disease diagnosis. Considering that three in 10 patients will not live to see their fifth birthday due to disease progression, the time to reach a diagnosis is far too long. In 2006, Rolfs founded CENTOGENE with the aim to address this significant need for earlier diagnostics.
“On the one hand, the story for our patients can only be changed if we develop a very sophisticated, robust, cheap, and easy diagnostic workflow that allows doctors globally to diagnose patients early,” Rolfs explains. “On the other hand, it’s really important that we systematically collect global knowledge around individual rare diseases because only this knowledge allows us to accelerate and support the development of new treatments.”
Changing the focus from Europe and North America to the world
Since starting in the rare disease field 25 years ago, Rolfs feels that not much has changed regarding the diagnosis of rare diseases. The reason, he says, is that there has been a lack of focus on countries outside of Europe and North America.
“Roughly 6% of rare disease patients live in Europe and around 7% live in North America. But the majority of patients are from countries outside these areas where the overall progress and success we typically see is not changing the lives of patients. There is often no infrastructure and still no genetic facilities. And most governments or insurance companies are not willing to pay the high costs of treatments. Our focus should be on these countries where we have to offer better solutions in the future.”
For example, of the 150,000 to 180,000 rare disease patients CENTOGENE identifies annually, many come from Arabic countries and have autosomal recessive diseases. The reason for this is rooted in the social norms that see a higher frequency of marriage within the same family. Moreover, the family size is significantly larger compared to Europe or North America.
Diagnosing rare diseases is quite a challenge
One of the key factors that have to be taken into account when diagnosing a rare disease is the genetic makeup of different ethnicities. “A mutation in the Caucasian population might have a significant functional impact and cause a disease, but the exact same mutation in the Mongolian population might be without any functional consequence,” Rolfs explains. “Therefore, it is important to get a deeper insight into the differences in genetic mutations within different ethnicities and populations.”
This means that a proper analysis and interpretation of the medical data is essential to enable an accurate diagnosis. While it is not challenging to sequence a genome anymore, the difficulty lies in the correct interpretation of the available data. The proper handling of data is extremely important to avoid misdiagnosis of patients.
“Each of us has about four million mutations in our genome, but luckily the overall majority of these mutations are without any functional consequence,” says Rolfs. “For every mutation, we have to prove that there is no functional consequence. This can be especially difficult for different ethnicities where the existing data banks lack information.”
Making data collection and analysis more efficient
By being globally active, CENTOGENE ensures that it collects data from various ethnicities to enable the diagnosis of thousands of patients with the same disease. Furthermore, to make its data interpretation as accurate as possible, the company combines its genetic testing with proteomics and metabolomics.
This so-called multi-omics approach allows CENTOGENE to better understand whether a given mutation causes a functional consequence on the protein or metabolite level. If the mutation reveals an impact on the proteome or metabolome, it is most likely harming the patient.
To simplify the diagnostic process from start to finish, CENTOGENE has not only addressed the challenges of data analysis. It has also developed a system that allows doctors to simplify the sample collection process.
“Doctors often deal with over 100 patients every day and are under significant time pressure,” Rolfs explains. “They need easy and robust information and a standardized process. We developed a simple system – CENTOGENE’s CentoCard – that requires just one drop of blood on a piece of paper to enable us to do the multi-omics analysis. This is pure simplicity and standardization. The doctors don’t have to think about anything. They just do the test, we analyze the sample, and send the report back to them.”
Raising global awareness for rare diseases on Rare Disease Day
Since founding CENTOGENE, Rolfs and his team have organized rare disease events. But this year is the first time they are hosting a global activity on February 29th, the international Rare Disease Day. In three cities around the world – in Berlin, Germany; Lahore, Pakistan; and Mexico City, Mexico – CENTOGENE will be raising awareness and sharing information on rare diseases with scientists, doctors, patients, patient organizations, and politicians.
In each city, the company is focusing on different aspects of rare diseases. “In Lahore, we would like to emphasize the burden of rare diseases and the need for better infrastructure for the diagnosis of patients,” Rolfs says. “In Berlin, we will demonstrate the use of innovative solutions and new technologies like artificial intelligence; and in Mexico City, we will concentrate on the huge importance and value of patient organizations.”
For 2021, CENTOGENE is also planning a rare disease film festival that will focus on changing the negative connotation of rare diseases. Using film as an emotional medium, the company is hoping to transfer the importance of knowledge and the visibility of rare diseases into society.
“Instead of the classical communication channels we have used in the past, like scientific papers, medicinal newspapers, and interviews, we decided to use movies instead because they can generate emotional responses and have a broader reach in society,” Rolfs explains. “Some patients are so impressive in the way they deal with their disease and this is something we want to make more visible.”
The future of rare diseases: Innovation lies at the heart of it all
Compared to other disease areas, the rare disease space is seeing a lot of innovation from pharmaceutical companies, says Rolfs. Innovations like RNA silencing and CRISPR technology are changing the rare disease landscape as more drugs enter the market.
However, the high costs of these innovative medicines are putting a great burden on healthcare systems worldwide. For instance, Novartis’ new drug Zolgensma for the treatment of spinal muscular atrophy is priced at $2M. These high costs, says Rolfs, are a problem that needs to be solved.
“On the other hand, diagnostics are getting better and genetics are getting cheaper. Once society better understands rare diseases and their impact, it can also start understanding why it’s important to pay these huge costs. And the very high level of innovation, the efficacy and the benefit we see in the treatment of patients are really extraordinary if we identify the disease early enough,” Rolfs concludes.
Images via Shutterstock.com
Author: Larissa Warneck, Science Journalist at Labiotech.eu