At the heart of Doha's Education City, a sprawling, sun-drenched campus of technology companies and universities, lies a healthcare facility that Qatar hopes will become a beacon of personalized medicine in the Middle East.
Defined by the giant glass and ceramic wings that adorn the building's exterior - a nod to the historic pearl trade in the nearby Arabian Sea - the Sidra Hospital was built to create a regional hub for the treatment of children with rare diseases.
"90 percent of our patients are children, and they are very, very sick children," said Dr. Khalid Fakhro, chief research officer and chair of the Precision Medicine program at Sidra.
"The thing about rare diseases is that they are very difficult to diagnose, so families go from one clinic to another, and sometimes they have to go abroad. Health economics studies have shown that it takes five to seven years to diagnose a rare disease. It's called the diagnostic odyssey."
Inherited blood disorders such as sickle cell disease and other rare conditions, often caused by a single gene mutation, are particularly prevalent in Arab countries due to a variety of factors, including the high rate of cousin marriage.
Although Qatar has taken several steps to address the problem, including mandatory pre-marital genetic screening that has been mandatory for all residents of the country since 2012, research has suggested that more than 50 percent of marriages in Qatar and the rest of the Arab world still takes place between blood relatives. family members.
Research from the Center for Arab Genomic Studies has previously shown that 2.8 million people in the Middle East are living with a rare disease, a significant public health burden.
But this has also led to one of the world's most innovative precision medicine initiatives, one that is already leading the way in quickly identifying the cause of newly identified rare diseases and uncovering potential treatment solutions.
While scientists have traditionally turned to rodents when it comes to understanding the biology behind a particular condition, Sidra's groundbreaking program is all based on one particular species of freshwater fish.
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Genetic similarities
The zebrafish is a species of roach that gets its name from the blue stripes on either side of its body. The species is commonly found in the waters of Southeast Asia and appeals to geneticists because humans and zebrafish share 70 percent of our genes.
"No one would imagine that a tiny fish from the Indian Ocean would be used in biomedical research," said Dr. Sahar Da'as, head of the Sidra Medicine Zebrafish Facility. "But of the genes we have in common, 84 percent are related to human disease genes."
This is not as much as mice or other mammals, but zebrafish do offer two crucial benefits.
Researchers can easily keep several thousand fish in a small laboratory, while they develop remarkably quickly. Within 24 hours of hatching as a single cell, they already have a head, tail and a beating heart. After five days they are fully formed and swimming around.
"Five days in the life of fish is equivalent to nine months in humans, while for rats and mice it would be about 21 days," says Da'as. "We can provide answers to patients within a week."
When a child with mysterious, unexplained symptoms - which can range from seizures to muscle loss to a deformed skull - presents to Sidra's doctors, their genome is immediately sequenced and screened for known gene mutations.
When it turns out that the patient is a carrier of a particularly unusual mutation, one that scientists have never encountered before, they begin the process of trying to replicate the biology in a zebrafish embryo.
Downstairs in the hospital's basement, rows of tanks are surrounded by an array of complex machines, some capable of imaging internal organs or measuring brain signals, and examining other patterns in their movement.
Depending on the mutation, the scientists will inactivate a particular gene or even inject the human gene into the fish, before waiting to see how it develops.
The team has even created a new breed of zebrafish, called Casper fish, after the cartoon ghost, that have been genetically engineered so that their skin is completely transparent. This allows them to accurately observe the formation of the internal organs.
"We can see the formation of the liver, pancreas, motor neurons and muscle development," Da'as explains. "From our imaging we can determine whether the brain size is smaller than expected as a result of a mutation.
"We can detect any biological changes that could affect a child's ability to walk by swimming. When fish have seizures, we can tell because their tails coil more quickly. We can do visual and auditory tests on them to see if their vision or hearing is normal."
Once they know what the gene does, the next step is to screen for potential treatments and then test them in the fish using existing drug databases to see if the various symptoms can be improved.
Da'as says she is currently treating a family of three brothers, all of whom have an inherited disease caused by a rare gene mutation that causes progressive nerve damage.
"The oldest siblings are 17 and 14 years old and they are wheelchair-bound, so it is too late to really change the neurodegeneration," she says. "But the youngest is seven and he still walks, but because of the gene he has low muscle tone.
"We simulated it in fish and discovered that treatment with a high dose of vitamin B12 could have a protective effect. So he is working on that now and we hope it will delay the symptoms."
Soon, Sidra researchers aim to go from identifying signs of a rare disease to delivering a treatment in just three months, a time frame that is astonishingly fast.
By comparison, the European Commission reported that it typically takes patients five years to receive a diagnosis. In the future, the hospital also wants to collaborate with pharmaceutical companies to conduct clinical trials with the aim of developing new, personalized medicines specifically targeted at patients with rare diseases.
"Earlier this year we finally received the necessary accreditation from the ministry," says Fakhro. "So now we have a facility downstairs that is fully ready to produce clinical-grade products and medicines for human use."
But Sidra's work is not just about understanding rare diseases, but also about the functions of relatively common genetic mutations, unique to populations in the Middle East, identified over the past decade through the Qatar Genome Program.
Dr. Said Ismail, the program's director, told the Telegraph that Qatar has now sequenced the genomes of more than 40,000 individuals, almost a tenth of the population.
Last year, a new paper described mutations in a gene called LMNA that are unique to the Qatari population. It showed that they cause a form of heart muscle disease called dilated cardiomyopathy, in which the heart chambers enlarge and lose their ability to contract, putting them at much greater risk of cardiac arrest during intense exercise.
"We used the zebrafish model to understand what happened in the heart as a result of the mutations," says Da'as. "It means we can screen patients and refer them to early interventions, such as avoiding vigorous exercise, following a low-fat diet and having regular check-ups with a cardiologist."
Ismail says Qatar is also working to identify specific gene mutations linked to hereditary cancers such as breast cancer and colon cancer.
"Many people know about the BRCA1 and BRCA2 genes associated with breast cancer, but the mutations used to detect the disease in Northern European populations are not found here," he says. "Ladies with these familial forms of breast cancer in the Middle East have other mutations, still within those genes, but different. So we have to design our own screening programs."
He predicts that many of the findings will bring public health benefits not only to Qataris, but to the entire Middle East and North Africa.
"The genetic discoveries made here will not only resonate with the people who live here," he says. "We have good representation within the Qatari population from much of the world, from the Gulf to the Atlantic.
"So I think we're in a very good position to represent genetic information relating to 400 million individuals living in this part of the world."
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