World first: gene therapy trial for rare disease patient

A patient at BHP’s Queen Elizabeth Hospital Birmingham (QEHB) has become the first person in the world to take part in a pioneering gene therapy trial for his rare disease.

Simon Smith, 45, was diagnosed with Ornithine Transcarbamylase (OTC) deficiency as a teenager.  

Although he defied medical expectations by living a full life in his 20s and 30s, in recent years Simon’s health took a turn for the worse.

This resulted in a referral to the QEHB Inherited Metabolic Disorders team.

“QEHB is a specialist regional centre for rare diseases, meaning we are involved in ground-breaking clinical trials that have the potential to transform patients’ lives.

“We have worked with Ultragenyx on a number of clinical trials, including the trial Simon has taken part in, which could potentially cure OTC deficiency.”

Dr Tarek Hiwot, Consultant in Inherited Metabolic Disorders

University Hospitals Birmingham NHS Foundation Trust, the BHP founder member which QEHB is part of, is the only Trust in the country involved in the trial, which involves a single intravenous injection that targets the liver.

The injection of a benign virus, DTX301, contains a treatment for OTC deficiency that helps the body to produce the correct proteins to help stabilise ammonia levels.

OTC deficiency has a number of symptoms, including an inability to stabilise ammonia levels in the body. This can cause issues with the liver, tiredness, and lead to delirium.

“Taking part in this trial has absolutely changed my life. I’ve gone from taking dozens of tablets a day to just three, and all my other symptoms seem to have gone.

“The care and support from Dr Hiwot and Research Charge Nurse Vishy Veeranna has been brilliant, and I can’t thank them enough.  The trial has literally saved my life!

Simon Smith

Simon took part in the trial in August 2017 and has regular follow-up appointments at the NIHR/Welcome Trust Clinical Research Facility, on the QEHB site, to assess how effective the treatment has been.

He was closely observed during and immediately after the transfusion, and has had weekly blood tests, which have monitored the effectiveness of the treatment and whether the body has rejected the treatment.

“Over the last four years, research within the Inherited Metabolic Disorders team has grown massively, with over 140 patients with metabolic disorders or other rare disorders currently involved in clinical trials.

“The clinical trial Simon has taken part in uses a one-time intravenous infusion gene transfer to deliver a working copy of the OTC gene to the liver, offering a potential new way to treat the disease that directly targets the genetic defect, rather than just treating the symptoms.

“If successful – as seems to be the case for Simon – the liver cells will produce the OTC protein that is needed for a normal life.”

Research Charge Nurse Vishy Veeranna

Although Simon’s sister carries the gene that causes OTC deficiency, she is less affected, with men more likely to be affected by the condition than women.

The trial is continuing, and is currently recruiting patients to its third cohort from twelve centres in the world, based in the United States, Canada, Spain and UHB.

The current standard treatments for OTC deficiency can include adhering to a strict low-protein, high-carbohydrate diet, daily medication, and in some cases dialysis to reduce high levels of ammonia in the blood.  

Our groundbreaking work in diagnosing, treating and curing rare diseases will be showcased in the atrium of QEHB on Rare Diseases Day, February 28.

At the Centre for Rare Diseases, patients are seen by specialists and wider multi-disciplinary teams in one visit.

With a Children’s Centre for Rare Diseases based at Birmingham Children’s Hospital, Birmingham Health Partners is the first partnership in the country to have specialised rare disease centres across the whole age range.

On Rare Disease Day 2019, interactive stands and displays in the QEHB atrium will showcase the work being done to diagnose and treat rare diseases across the UHB sites.

For more information about Rare Disease Day, visit