By examining the cell cultivation dishes, the researchers were able to observe how the patients’ cells behaved and developed from stem cells to nerve cells and compare them with cells from healthy controls. They found that the diseased cells matured much more slowly, sent out shorter projections and were much less mobile. “It’s already known that DCX affects the ability of neurons to migrate, but we can now show that DCX plays a much greater, broader part in brain development than that,” says Dr Falk. “Our hypothesis is that it’s this, the damaged nerve cells’ resistance to maturation that causes the disease.” Since there are no relevant animal models for lissencephaly, the reprogramming technique has been essential to the study of lissencephaly’s underlying pathogenesis. At Dr Falk’s laboratory, the method is used to also study other congenital diseases that affect the brain, such as autism and Down syndrome. In future projects, the researchers hope to study how diseased cells can be modified to act as healthy cells. “What many developmental diseases have in common seems to be the failure of brain cells to mature at the same rate as they do in healthy people,” says Dr Falk. “Trying to influence the cells so that they behave like healthy cells is the first step towards some kind of therapy for these diseases.” The study was a collaboration with Karolinska University Hospital, Uppsala University, SciLifeLab and the Salk Institute for Biological Studies in the USA. It was financed by several bodies, including the Swedish Foundation for Strategic Research, the Åke Wiberg Foundation, the Tore Nilson Foundation, the Jeansson Foundations, the Thuring Foundation and the Swedish Research Council, and through the KID and SFO funding schemes.