A new study on treating pain with a unique stem cell connection caught my attention. The paper was from a team at Pfizer led by Edward B. Stevens.
Talk about bench to bedside, these researchers went all the way from patients to patient somatic cells to reprogrammed IPSC to neurons to model pain in a dish and then test a drug in a dish, and then finally to test the drug in the patients. The drug in questions is the Nav1.7 blocker, PF-05089771.
The team found that neurons made from IPS cells generated from patients suffering from inherited erythromelalgia (IEM) exhibited differences in activity compared to controls. While I’m not sure that we can call these excitability differences literally “pain”, measuring them may serve as a useful readout assay for studying drugs that could treat pain.
You can see one readout of the differences in the IEM patient neurons versus controls in Figure 2B above.
A logical next experiment is to gene edit the patient cells to revert the mutation back to wildtype and examine the phenotype. Conversely, it makes good sense to using CRISPR to recreate the mutations by gene editing in other IPSCs, differentiate them into neurons, and examine the phenotype there. This could facilitate examining much larger numbers of cell samples from different individuals, something normally hard with rare diseases.
Overall, it’s a preliminary but very cool study. An interesting broader question is whether direct cell therapy based on IPSCs will catch up in the future to the positive impact already being had from disease modeling and drug testing.