A potentially revolutionary and “exciting” therapy for a rare brain disease has shown promise prior to a clinical trial, an international conference has heard.
Professor Brian Bigger, of the University of Manchester, UK, told the American Society of Gene & Cell Therapy that the safety and feasibility of the investigational gene therapy for Sanfilippo disease type A (MPSIIIA) is becoming clearer, as a formal clinical trial gets underway.
The investigational gene therapy, which involves harvesting patient’s blood stem cells, was delivered to a two-year-old under a special licence at The Royal Manchester Children’s Hospital in 2019 by Professor Rob Wynn, following more than ten years of development and pre-clinical work at the university.
The patient was followed for a year after the treatment and preliminary results have revealed rapid engraftment of the gene modified cells and greater than 25-fold of median normal SGSH enzyme levels achieved in the blood.
At six months after treatment, cerebrospinal fluid levels of SGSH enzyme were at the upper end of normal range.
The treatment uses a lentiviral vector to deliver the patient’s missing SGSH gene to the blood stem cells in the laboratory. The manufactured gene-modified stem cell product is then transplanted into the patient.
The stem cells then regenerate the immune system, which means the patient has a working, and potentially permanent, copy of the gene.
Prof Bigger said: “These results are promising and provide some hope for these children whose condition was previously thought to be incurable. The trial is the critical next stage, but it’s true to say we are excited.
“Sanfilippo Disease is an appalling disease which causes misery to these children- so the prospect of a treatment is tantalising – especially when it was thought for years that no treatment would be possible.”
In the phase I/II trial, between three and five children, all aged under two years and who have severe MPSIIIA, will be given the gene therapy transplant.
The first patient was recruited in early January 2020 and their blood stem cells were harvested and modified prior to transplant back into the patient this month (May 2020). The child will be assessed over the next three years.
The trial is being sponsored by The University of Manchester and the gene therapy product is being manufactured at University College London Great Ormond Street Hospital Institute of Child Health using the expertise of Professor Thrasher’s specialist gene therapy laboratories.
Source: University of Manchester
Leave a Reply