Gene Therapy Benefits Children with Sanfilippo Syndrome, Phase 1/2 Trial Shows

Ashraf Malhas, PhD avatar

by Ashraf Malhas, PhD |

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Sanfilippo gene therapy

A gene therapy led to the brain producing the proper form of an enzyme whose faulty version causes Sanfilippo syndrome type B, a Phase 1/2 clinical trial showed.

The therapy,  rAVV2/5, also improved the neurological condition and behavior of the four preschool-age children involved in the study (ISRCTN19853672), researchers said.

And it generated the proper version of the enzyme long after researchers delivered it to the brain. In addition, it was safe, and the children tolerated it well.

A gene mutation leads to the defective enzyme that causes Sanfilippo syndrome, whose full scientific name is mucopolysaccharidosis type IIIB syndrome. The enzyme is known as α-N- acetylglucosaminidase, or NAGLU.

Researchers wanted to know if the gene therapy was safe for children with Sanfilippo syndrome type B, and if it could display signs of effectiveness.

The study, “Intracerebral gene therapy in children with mucopolysaccharidosis type IIIB syndrome: an uncontrolled phase 1/2 clinical trial,” was published in Lancet Neurology.

Researchers said the children were aged 20, 26, 30 and 53 months when the trial began. The team used a harmless virus to deliver the injected therapy to their brains.

The children also received immunosuppressants to prevent their immune system from destroying the virus.

Researchers assessed the children’s NAGLU enzyme activity, brain growth, cognition, and ability to tolerate the gene therapy for 30 months. They found no inflammation, excess fluid, or cell death at the virus delivery sites.

The enzyme’s activity rose to 15-20% of what normal children experience, the team said. They said it was noteworthy that the youngest child showed the best results.

Another finding was that the treatment improved the children’s neurological symptoms, development and behavior.

Although the children experienced 125 adverse events, none was a serious reaction to the therapy, the researchers said.

The said they considered the trial an “essential first step towards the design of future protocols aiming to obtain full reversal of mucopolysaccharidosis type IIIB syndrome through the treatment of patients younger than 2 years, which seems to be the best window of opportunity, and by the delivery of NAGLU both within and outside the brain.”