IND-enabling study of subretinal delivery of human neural progenitor cells for the treatment of retinitis pigmentosa

The major scientific progress during this reporting period has been the re-manufacture of clinical grade neural progenitor cells derived from the human fetal cortex (CNS10-NPC) and the establishment of the intended doses for the toxicology study. Clinical grade cells are required for both pre-clinical, and clinical phase. The first batch of clinical grade CNS10-NPC did not pass the cell lot release quality requirements. Specifically, karyotype analysis of final product showed 35% of cells with an extra chromosome. Karyotyping of in-process samples showed that this emerged late in the production run after the last in-process assessment at passage 27 (p27) but before freeze down at p29. Clinical grade cell production was repeated accelerating freeze down to passage 25, before the emergence of this variant. An in-process sample was analyzed for karyotype at passage 23 and the karyotype defect was not detectable. This new batch has passed the most concerning and critical safety tests. It also meets the requirements of cell viability and concentration, and cell line identity. Altogether, these data indicate that the second lot manufacture has been successful. A pilot dosing study in a retinitis pigmentosa rat model (Royal College of Surgeon -RCS- rats) has been completed. RCS rats were given a unilateral subretinal injection of different doses of research grade CNS10-NPC. The combined data from this study showed a clear dose response, which allowed the determination of a target dose for the upcoming toxicology study. In summary, all the data from the pilot dosing study point to 60,000 CNS10-NPC being the optimal dose tested in the rat. Therefore, this dose will be used to establish the target in the pigs and human as well as the basis for design of the pivotal toxicology study