For a decade researchers have heralded the promise of stem cells as the basis of medical breakthroughs-to-come. With the discovery of new stem cell reprogramming techniques in 2006, creation of stem cells taken directly from living people finally became a reality, and scientists all over the world started the race to create stem cells from individuals with a variety of specific conditions. For autism, stem cells made their mark in October 2010 when scientists in California generated stem cells (called inducible pluripotent stem cells, or iPSCs) from skin samples of people with a condition associated with autism spectrum disorder, Rett syndrome. The stem cells offered some of the first clues to what autism may look like at a cellular level, and provide a remarkable new way to test autism treatments.
Stem cells are primitive cells that serve as the supply source for mature cells in our body. Stem cells are able to do this because of two special properties – they can self-renew, meaning they can divide over and over to create more stem cells just like themselves, and they are multipotential, meaning that the daughter cells they give birth to can adopt different fates depending on the signals they receive. For the public, stem cells are perhaps best known as a means to directly supply replacements for cells lost due to disease, such as in Parkinson's or spinal cord injury. However, stem cells are having perhaps a bigger impact not by becoming the actual treatment itself, but by providing researchers with the opportunity to study unlimited quantities of cells associated with different conditions. Thus, stem cells provide an invaluable resource by creating new laboratory models, and for screening drugs. For example, such “diseases in a dish” have already been made using stem cells from patients with Lou Gerhig's disease and Spinal Muscular Atrophy.
Researchers from Salk Institute and UCSD have now published their initial successes creating, studying, and treating iPSC-derived neurons from patients with Rett syndrome. The investigators, led by Alysson Muotri, Ph.D., found striking differences in the iPSC-Rett neurons. They had smaller cell bodies and fewer points of communication, or synapses, between them. The neurons also functioned differently, showing fewer spontaneous bursts of activity.
Carol Marchetto, Ph.D., the paper's first author, took the power of iPSCs further. She applied two drugs that compensated in different ways for the effects of the mutated gene, MeCP2, that causes Rett syndrome. Application of insulin-like growth factor 1 (IGF1) has previously been shown to delay the onset and even reverse the neurological symptoms in a Rett syndrome animal model. The addition of IGF1 to Rett-derived neurons resulted in more synapses. Similarly, a type of antibiotic (Gentamicin) causes cellular error-correction mechanisms to effectively turn a blind eye to mutations when creating proteins. By altering the effects of mutations that would normally have stopped the creation of MeCP2, this drug also produces more synapses in the Rett-derived neurons.
The stem cell field is in its infancy, but with new techniques making this complicated process easier and easier, stem cell researchers all over the world are beginning to model autism and its related disorders. In 2010 scientists also published initial stem cells findings on Fragile X, Angelman and Prader-Willi syndrome, all conditions that have autism as a feature. The significance of having these stem cells is not just that we are now closer to revealing the biological mysteries of autism but, as the California researchers showed, that the stem cells can directly be used as a way to screen for therapeutics based on the specific deficit found in a person's cells. This opens the future to design of individually-tailored treatments and makes personalized medicine for autism no longer only a dream.
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