A baby boy with an extremely rare genetic disorder is making “incredible” progress after becoming the first infant to receive a new gene therapy at a renowned British hospital – paving the way for optional avenues to treat babies with severe liver genetic diseases.
Fourteen-month-old Tomas was diagnosed with ornithine transcarbamylase (OTC) deficiency when he was a few weeks old, becoming just one of 15 each year diagnosed with the disease.
An OTC deficiency is when ammonia, a waste product that is generated when the body breaks down proteins, builds up in the blood.
Ammonia is usually processed in the liver and removed through urine but patients with the condition have a genetic deficiency in the protein in the liver which is responsible for detoxifying ammonia, allowing ammonia to build up, which can be toxic.
It can cause life-threatening complications including brain damage, coma or seizures, if left untreated.
The Independent reports that treatment can include removing protein from the diet and medication, known as “scavenger therapy”, but in severe cases, this is not enough. Some patients, especially baby boys with the condition, sometimes require a liver transplant.
It was thought that a transplant would be the only option for Tomas, until he was enrolled in the ground-breaking gene therapy trial at Great Ormond Street Hospital (GOSH) in London.
Symptoms of the condition typically start to show shortly after birth, including extreme tiredness, inability to feed and vomiting.
Tomas’ parents noticed something was wrong when he was just one-week-old, they said.
“He became unresponsive at home and wouldn’t open his eyes, which was really scary.
“We called an ambulance, and took him to our local hospital, but when we first arrived, the doctors couldn’t determine what was wrong with him.
“We spent the whole day there, from morning until evening, while they suspected an infection but were not certain. Tomas was getting worse, and unfortunately, the hospital couldn’t help us. That’s when we were transferred by ambulance to GOSH.
“Within an hour or two at GOSH, they told us that his ammonia level was too high.”
Medics at the world-renowned children’s hospital diagnosed him with OTC deficiency and asked if his parents wanted to enrol him on the OTC-HOPE trial.
The trial is examining the gene therapy which is delivered via an infusion to reach the patient’s liver cells, and has been designed to restore the damaged OTC gene with a functioning copy.
Called ECUR-506, the therapy is a new way of inserting a gene – the functioning OTC gene copy is designed to be inserted very precisely at a specified location in one of the chromosomes.
It is hoped the treatment will be comparable to the results seen in a liver transplant among OTC deficient patients – but using a one-time treatment instead.
Tomas received the treatment last summer, and six months later, said his mother, he no longer needs the steroids and is making good progress. “He no longer needs a special diet and scavenger medications either. We recently celebrated his first birthday.”
Principal investigator for the study, Julien Baruteau, consultant in metabolic medicine at GOSH and clinician scientist fellow at University College London Great Ormond Street Institute of Child Health, said: “We’re pleased to see Tomas’ progress since having the gene therapy. Standard of care for babies with neonatal OTC deficiency relies on liver transplantation in infancy, a procedure with significant risk of complications.
“This novel gene therapy approach might enable babies with the condition to avoid this.
“I’m hopeful that Tomas will continue along this encouraging trajectory and that other babies who enrol in this study will have similar experiences.
“To our knowledge this is the first time a baby has received a liver-directed gene editing therapy. This novel technology may herald new avenues to treat babies with severe liver genetic diseases.”
Baruteau is presenting initial data to the Annual Clinical Genetics Meeting in Los Angeles tomorrow.
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