Meet Karla De Lautour today and you’ll find a lively seven-year-old who enthusiastically takes to her bike, or seizes any opportunity to bounce on her trampoline.
- Doctors could not figure out how to treat Karla De Lautour’s rare combination of arthritis and liver problems
- They referred her to the Garvan Institute to participate in a study on genetic auto-immune conditions
- The scientists mapped her genome and discovered a drug already existed to treat the cause of Karla’s problems
A few years ago, she could barely walk 20 metres without needing her mum to carry her.
“We always had a stroller with us till she was about four, everywhere we went,” Barbara Guerra said.
Until recently, Karla suffered from swollen joints, and an inflamed liver: an unusual combination of autoimmune conditions that caused her enormous distress and flummoxed her doctors.
That is until a team of scientists at Sydney’s Garvan Institute were able to identify the exact treatment to bring her relief.
They are among a growing number of researchers joining forces with doctors to find personalised therapies, particularly for people with unusual conditions.
Karla was first known to them only by her genome, which they decoded in their lab as part of a study into rare auto-immune conditions.
When Chris Goodnow, who leads the programme, recently met Karla face-to-face he was overjoyed to discover the case study with the painful joints had transformed into “a fantastic, chirpy, totally normal, seven-year-old.”
Karla’s condition first showed itself when she was 18 months old and had to be hospitalised with an inflamed liver.
Once doctors were able to stabilise that, her joints flared up.
Karla’s rheumatologist Davinder Singh-Grewal said they had tried everything and come to the end of the line.
“She had a lot of pain, she was stiff every morning and it really was affecting her ability to live a normal life.”
He suspected a genetic disorder might be to blame for Karla experiencing such an unusual mix of symptoms so early in life and put her forward as a candidate for Professor Goodnow’s programme in Sydney.
‘One single letter out of 6 billion’
According to Professor Goodnow, the ability to unravel someone’s whole genome did not exist five years ago, but as the technology emerged, he applied for funding to spend four years sequencing the DNA of a few hundred people with rare conditions.
“To see what we learn, either of clinical benefit or at least of advancing our understanding of auto-immune disease as a whole,” he explained.
Luckily for Karla, when his team decoded her genetic make- up, they found a single mutation in part of the genome that previous studies had shown was pivotal in controlling the body’s immune system.
“One letter, one DNA nucleotide [in that genome] was different from anyone else that’s ever been sequenced, including her mum and her dad, who we sequenced in parallel,” Professor Goodnow said.
Not only could they see that the faulty gene was causing an important brake on her body’s immune system to fail, but they also knew a drug, called Abatacept, already existed to counter the problem.
Strict clinical guidelines for administering the drug, which is used for treating rheumatoid arthritis, meant Dr Singh-Grewal could not offer Karla the cure she needed without first trying several other drugs that would not have been as effective.
“Had they not sequenced the genome, she would have continued on in pain,” Dr Singh Grewal said.
As it is not the first-line treatment for children with arthritis and has not been subject to clinical tests on this group of patients, Karla’s doctors needed to get ethics approval from the hospital.
Within two months, her condition had improved.
“It was quite remarkable within a short period of time the arthritis had melted away and she was running and skipping around like a normal child,” Dr Singh-Grewal said.
Not only is the medication directly addressing the problem that was causing her complaints, rather than helping ease the symptoms, it is also much easier for her to tolerate.
“It feels better because it makes my pain go away and it feels comfortable,” Karla said.
Researchers leading clinicians
Not only has Karla’s case added to the body of scientific understanding about her autoimmune condition, but it has also shown the value of scientists working closely with doctors to find treatments targeted to individual patients.
“What Karla illustrates so beautifully is this new era where research, very basic research … is suddenly immediately and immensely helpful for patients and their doctors,” Professor Goodnow said.
Charlotte Slade, an immunologist at the Royal Melbourne Hospital, said Karla’s case showed that it was possible to find a single gene causing a patient’s autoimmune condition and quickly identify the right treatment.
She thinks as the ability to analyse genetic data improves, the ability to find these targeted therapies will become more widely available.
“I see in the next 10 years or so that we should be able to really precisely diagnose patients from their genetic information and their clinical features and have a much more streamlined approach to treatments,” she said.
Many autoimmune conditions are not as simple as Karla’s, and instead of having one single faulty gene, they are caused by many genes throughout a patient’s DNA.
Professor Goodnow said the next step is for genetic science to move towards being able to identify treatments for more complex illnesses.
“This process is underway with Karla contributing in some way to that,” said Professor Goodnow.
Dr Singh-Grewal agrees that personalised medicine is now the holy grail in the treatment of arthritis, many auto-immune conditions and a range of other diseases.
“In many of the conditions that I treat, that’s not yet possible, but it remains the hope for the future,” said Dr Singh-Grewal.