An article released in Science last August (Induced Pluripotent Stem Cells Generated from Patients with ALS can be Differentiated into Motor Neurons) prompted Time Magazine to name the discovery the No. 1 Medical Breakthrough of the Year. Collaborators at Harvard University and Columbia University based their research on a previous breakthrough that suggested the feasibility of reprogramming somatic cell nuclei into an undifferentiated state by a process called somatic cell nuclear transfer. While the Obama administration recently reversed the limits Bush had previously imposed on embryonic stem cell research, it is of no consequence to this team of scientists, who opened the door to stem cell research involving skin cells rather than human embryonic cells.
The motivation for their ground-breaking work is the state of research on ALS, or Lou Gehrig’s disease. Once referred to as an orphan disease, ALS is finally getting the attention it deserves as an incurable and mysterious neurodegenerative disease. The cause of the disease is currently unknown, but a supply of human motor neurons carrying the genes responsible for the disease would be highly beneficial to research and eventual treatment. Unlike other disease research where the affected cells can be removed from patients and examined, obtaining a diseased model of a motor neuron or glial (support) cell is unheard of making investigation of degeneration of the cells very difficult.
The team of scientists used skin cells extracted from two elderly ALS patients and transduced the fibroblasts with four genes previously determined to return cells to an undifferentiated state. This is possible because embryogenesis is not dictated by genetic events; it is actually reversible! Imagine that! From the skin cells, the scientists were able to produce iPS colonies (induced pluripotent stem cells), which are very similar to ES cells in morphology and expression. One success after another, they pressed on in hopes of differentiating these cells into motor neurons and glial cells.
I had the opportunity to work with the team of collaborators at Columbia University two summers ago when they were developing a concrete procedure for the differentiation of mouse and human ES cells into motor neurons. It was with this method that the scientists ultimately created motor neurons from simple skin biopsies. While this research was done on patients who expressed the SOD1 allele (or the gene pinpointed in familial ALS), 90% of ALS cases are sporadic, meaning there is no genetic history of the disease. The research is far from null though; it actually provides great insight into the sporadic form of the disease, which is believed to be caused by a combination of genetic and environmental factors. Once a more stable method of reproduction is determined, this research should have a great impact on research and clinical trials for patients with ALS and other neurodegenerative diseases.