At WORLDSymposium 2023, Brian Bigger, Chair in Cell and Gene Therapy at University of Manchester, shared that its investigational gene therapy for Sanfilippo syndrome has “shown promising early results in a proof-of-concept study.”
The study was funded by Orchard Therapeutics, sponsored by The University of Manchester, and conducted at Manchester University NHS Foundation Trust.
According to a press release from the University:
The study found four out of five patients diagnosed with Sanfilippo have continued to gain cognitive skills in line with development in healthy children after being given the investigational gene therapy, OTL-201.
However, the researchers urge caution as the majority of patients have not reached the age of 4-5 years where the most severe stages of disease progression typically present.
The trial patients were 6 to 24 months of age at the time of administration of OTL-201, and the preliminary results are based on a median follow-up of 2 years (range: 9-30 months).
Patients enrolled in the trial will be followed for a minimum of 36 months during which time the study investigators will continue to report additional biochemical and clinical outcomes.
The rare genetic metabolism disorder called Sanfilippo syndrome Type A- or Mucopolysaccharidosis Type IIIA (MPS-IIIA)- is a genetic disease with devastating effects on the central nervous system affecting around 1 in 70,000 children.
Patients with MPS-IIIA have a mutation in the SGSH gene, causing them to lack an enzyme which normally breaks down large sugar molecules.
These molecules then accumulate in the cells of the body causing irreparable damage to many organs including the brain, leading to inflammation and damage to brain tissue.
The investigational gene therapy OTL-201 works by collecting a patient’s own blood stem cells and inserting a working copy of the SGSH gene using a modified virus, known as a lentiviral vector.
The patient’s modified blood stem cells, now including a working copy of the SGSH gene, are then given back to the patient.
This enables patients to then make this missing SGSH enzyme and provide it throughout the body from blood cells made in the bone marrow. These stem cells can make monocytes, which are specialised blood cells able to enter the brain. This means they can release SGSH enzyme to potentially help stop damage to the brain.
The results showed:
- An improvement in neurocognitive assessments compared with natural progression of the disease in one of the children at 18-months post-treatment.
- Three additional patients are currently within the normal cognitive development range at 9 to 18 months post-treatment, but require longer follow-up to assess outcomes.
- After a median of two years, OTL-201 which was generally well tolerated in all the patients, achieved sustained engraftment in the bone marrow.
- Higher amounts of the SGSH enzyme were seen than would be normally found in the blood and cerebrospinal fluid of healthy children.
Read the complete press release regarding the early trial results from the University of Manchester.