Pelizaeus-Merzbacher Disease: Clinical Program
Completed: Phase I Clinical Trial in PMD
The Phase I clinical trial, conducted at the University of California, San Francisco, transplanted HuCNS-SC® cells into four patients with connatal PMD. Connatal PMD is the most severe form of the disease and patients are usually diagnosed soon after birth with pronounced neurological dysfunction. The patients were followed for 12 months after transplantation in the Phase I study, and thereafter were enrolled in a 4-year, long-term, follow-up study.
The 12-month Phase I post-transplant results indicated a favorable safety profile for the HuCNS-SC cells and the transplantation procedure. Analysis of MRI data showed changes consistent with increased myelination in the region of the transplantation, which progressed over time and persisted after the withdrawal of immunosuppression at nine months. The results support the conclusion of durable cell engraftment and the development of donor cell-derived myelin.
In addition to the MRI findings, neurological examinations showed either stable or modest gains in motor or cognitive function in all subjects compared to pre-transplant assessments. The subject with the most pronounced post-transplant clinical change demonstrated the ability to follow two-step commands, speak audible words, and had improved truncal support, as well as the ability to take steps with assistance. Neuropsychological assessments also showed small but measurable gains in select subtests. Overall, these clinical gains, though modest, are not expected in the setting of a progressive, severe neurodegenerative disease.
Interim data from the long-term follow-up study, which was presented in August 2013, showed that the MRI evidence of myelination noted at 12 months in the Phase I study continued to persist more than 2 years after transplantation of the HuCNS-SC cells. In addition, there were no safety concerns and the gains in neurological function reported after one year were maintained. The neurological and MRI changes suggest a departure from the natural history of the disease and signals of a possible biological and clinical effect.
The design of a controlled study to demonstrate clinical efficacy of HuCNS-SC transplantation in PMD has been discussed with the FDA. Future clinical development in PMD and other possible leukodystrophies are under consideration by the company.