RARE Daily

Study Shows Promise of N-of-1 Gene Therapy

July 1, 2024

A study of a child treated with the first experimental N-of-1 gene therapy for the ultra-rare neurodegenerative condition spastic paraplegia type 50 shows it has halted progress of the disease a year after treatment.

SPG50 causes developmental delays, speech impairment, seizures, progressive paralysis of all four limbs, and is typically fatal by adulthood. Approximately 80 children around the world are affected by this genetic condition.

In the study published in Nature Medicine, the clinical team at The Hospital for Sick Children in Toronto and others report since treatment, the patient Michael experienced no serious side effects and his condition does not seem to be progressing further. They also report he has begun to show potential signs of improvement.

“While these ultra-rare diseases are unique, our workflow provides a road map for gene therapies that could help many of the thousands of children in Canada with rare genetic conditions,” said Jim Dowling, staff physician in the Division of Neurology and senior scientist in the Genetics & Genome Biology program at SickKids.

Doctors treated Michael with the gene therapy three years after his initial diagnosis. They said the results highlight how gene therapy can be developed quickly and personalized for individual patients with rare genetic conditions.

The study, though, is tempered with the reality of conducting single-patient trials. It acknowledges the limitations of such studies, as well as ethical considerations. Perhaps more limiting, though, are the financial considerations.

The CureSPG50 Foundation estimated that the total cost of the project for preclinical development was $2.5 million (Can $3,500,000), and the cost of the clinical trial was approximately $181,000 (Can $250,000), plus expenses related to concomitant medicines (tacrolimus and sirolimus) and in-kind contributions that were difficult to estimate.

“While our overall workflow provides a road map applicable to other genetic diseases, it is challenging (given the cost) to consider this as a widely iterative strategy for ultra-rare disease gene therapy,” the scientists write. “Cost-reducing innovations are clearly needed. Manufacturing expenses are extremely high, particularly related to batch production for small patient numbers. A paradigm leap in production is likely required to make gene therapy viable for the largest number of patients.”

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