Latvian geneticists are also working on the discovery of new and rare diseases, but for this to be possible, international cooperation is crucial, as explained by Dr. Inna Iņaškina, a senior researcher at the Biomedical Research and Study Center of the University of Latvia, and Dr. Ieva Mičule, a geneticist at the Medical Genetics and Prenatal Diagnostics Clinic of the Children’s Clinical University Hospital, in an interview on Latvian Radio’s program "Zināmais nezināmajā."
One in 2000
The charity marathon *"Dod pieci!"* will soon begin this year, aiming to raise funds to provide immediate assistance to people suffering from severe diseases, many of which are also rare.
There are more than seven thousand known rare diseases worldwide, and most of them are genetic. A disease is considered rare when it affects no more than one in two thousand people. Meanwhile, ultrarare or extremely rare diseases are found in no more than one in fifty thousand people, Mičule explained.
With each passing year, new rare and ultrarare diseases are being discovered, but this does not mean the diseases themselves are increasing—modern medicine is simply better at recognizing, identifying, and highlighting them.
"For example, once it might have been thought to be a single disease, but now, thanks to genetic diagnostics and the ability to look into the human genome, we see that these are actually different diseases related to different genes. And so, they are increasing," said Iņaškina.
Anything Can Go Wrong
In the context of drug development for rare diseases, the term "orphan diseases" is used, indicating that these diseases are so rare they have been largely neglected. "To start treating these diseases, to develop drugs for them, a huge investment is needed—disproportionately large compared to the number of affected individuals, which is why these diseases are grouped as a separate category," Iņaškina pointed out.
Not all rare diseases are inherited—there are also rare infections, for example—but when talking about inherited conditions, Mičule noted that rare diseases can affect any organ or system in the body.
"Anything in a person can be misformed, not functioning properly. Any system can be involved," Mičule explained.
From Symptoms to Mice
Iņaškina shared her experience of discovering a new disease when a particular family reached out to her colleague, Dr. Baiba Lāce, a geneticist and biology PhD. "There was a family whose symptom complex didn’t match any known disease. Dr. Lāce contacted several specialists worldwide, consulted and corresponded with them, and later Professor Karsten Bonnemann came to examine the family in person and indeed said – this is something new," Iņaškina recounted.
Geneticists then began investigating what the family was suffering from, examining the exome of the entire family, both affected and healthy members.
"Back then, they looked at the exome, not the genome. The genome is all the genetic information of a person, but the exome is a smaller part that specifically involves the coding regions. They once studied the exome, but science and diagnostics have advanced, and now the full genome is more commonly examined," explained Iņaškina.
Fortunately, it was enough to study the exome to identify what differed in the genomes of the affected family members compared to the healthy ones, and this was consistent across all affected members. Eventually, geneticists pinpointed a specific gene previously linked to other diseases, which was now related to something completely new.
"Then we began looking for research groups studying this gene and collaborated with them. They found another family in Germany with very similar symptoms," Iņaškina said. In the end, two disease modeling experiments were conducted on mice—one in Baltimore, one in Riga. These models showed all the symptoms of the human disease.
"It doesn’t always happen that animal models perfectly mimic human problems and symptoms. We were lucky; our models were very, very similar. That’s the final proof—an animal model. Once that is done, there are no more questions. Now, up to 20 families worldwide have been identified with this disease, but it is definitely very rare," Iņaškina said.
The discoveries are still being documented, but the work of scientists is challenging because researching such rare diseases is hard to fund. If only one family in a country or just 10 families worldwide are affected, it takes significant effort—and even luck—to convince people to invest in this research.
"Money is a major issue because there needs to be continuity. We study these specific diseases even five or ten years later, but nowadays it’s difficult to plan for something like that," Iņaškina admitted.
Without International Contacts, Nothing
Iņaškina explained that the main problem in discovering rare diseases used to be the very small number of patients. If a country has just one family with specific symptoms, researchers have very limited opportunities to draw conclusions.
Today, things are different. Geneticists and scientists easily communicate with colleagues in other countries.
"Scientists now have an internal ‘Facebook’ where they can directly message people—‘I have a family with these and those symptoms that don’t match any known disease, but we’ve researched and found a suspicious variant in such and such gene.’ After some time, you might find groups from Japan or Canada with similar families and maybe even with the same or similar variant in the same gene," Iņaškina explained.
Thus, thanks to international collaboration, diseases are being discovered that, in the past, might have remained a mystery.
The Work Never Ends
"Right now, we also have families with symptoms indicating that something is wrong with their genetic material, that it’s not functioning as it should. There are some suspicious genes, and we are contacting researchers in other countries, and the process is ongoing," Mičule noted.
At the same time, she emphasized that just finding and proving the cause in a particular gene doesn’t end the work—defining the disease and its cause is only the beginning.
"The work doesn’t stop there because we might only know about five or maybe ten families of certain ages. If they are adults, we might know more about them. If they are children, young children who have these symptoms right now, we don’t know much about the disease yet. We have to wait for them to grow and see what symptoms appear in a year, five years, and ten years. So research into the genetic cause of a disease doesn’t end; it’s just the beginning," Mičule explained.
Listen to the Latvian Radio program in Latvian here.
Source: lsm.lv Photo: Pixabay.com