Following their clinic visit, patient blood samples are de-identified and sent to the laboratory of at Cedars-Sinai. Here, Dr. Clive Svendsen’s lab begins the processes of transforming the blood cells, known as peripheral blood mononuclear cells (PBMCs), into induced pluripotent stem cells (iPSCs; see figure below). Finally, the iPSCs themselves are converted into motor neurons (MNs)–the exact cell type observed to degenerate in ALS. Motor neurons derived from each of our patients can then be sent out to the ‘omics labs to undergo an unprecedented level of interrogation.
While producing several iPSC/ motor neuron lines at a time is reasonably typical for a lab, Answer ALS tasked the Cedars-Sinai lab with the goal of scaling–up to handle dozens of patient samples at a time. To accomplish this goal, the lab has achieved two major milestones over the past number of months. Firstly, they are now staffed and equipped to handle a much larger workload. Secondly, the lab has successfully optimized the process of converting iPSCs into motor neurons with the end result that i) the transformation occurs at a faster rate and ii) is more efficient–more motor neurons can be generated from each patient. Given the scale of the Answer ALS study, these two accomplishments will make a substantial contribution to our success.
iPSCs derived from Answer ALS patient stained with pluripotency markers Oct4, SSEA4, Sox2 and Tra-1-81