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How to Cure an Autistic Disorder
The term ‘neurodevelopmental disorders’ refers to a group of devastating diseases that are caused by a disturbed development of our brain. Well-known examples of neurodevelopmental disorders are intellectual disability and autism. Many of these disorders are the consequence of an error in one of our 20.000 genes. Over the last years, we have become very experts in unwinding the genetic puzzle in patients and many new autism and intellectual disability disorders have been described. As such, thousands of patients spread over the globe have received a genetic diagnosis. Without exception, a genetic diagnosis brings tremendous relieve to the families. Finally an end to an often years long search on the origin of the disorder. Not uncommonly, parents connect with parents of a similarly affected child, much facilitated by the availability of social media.
The success in gene identification created a strong quest for therapy. Needless to say that identifying the genetic cause raised hopes for a treatment for the disorder. So far, the expectations lag far behind fulfillments of the scientific word and biotech industry. In fact, curing an inborn brain disorder turns out much more complicated than anticipated. This is why we decided to reflect on the scientific breakthroughs that led to the initiation of clinical trials in the fragile X syndrome, a most frequent form of genetic autism and intellectual disability.
No disease will be cured without a proper understanding of the molecular function of the causative gene. Chapter two of the book Fragile X Syndrome, edited by myself and Rob Willemsen, was written by key researchers involved in the identification and functional studies of the gene involved is a very elegant introduction into the field of genetic discoveries. It is highly interesting, from a scientific as well as from a historic viewpoint. Authors David L. Nelson, Michael R. Santoro, and Stephen T. Warren take us back 25 years and more in time to describe how they discovered the first repeat expansion disorder. The concept that a disorder was due to “growing” DNA was completely new in that era. Yet this knowledge helped to solve some of the mysteries of the genetic anticipation that runs in some families. In addition, many oddities associated with the discovery of this gene are highlighted. We are pleased to share this chapter “Fragile X Syndrome Genetics” with you.
No theory has raised higher expectations for a cure than the so-called mGluR theory of fragile X. Based on the observation that protein translation in neurons of patients is exaggerated; the elegant theory that restoring cellular homeostasis could correct the symptoms of the disorder was unanimously welcomed in the field. Animal work showed the validity of the theory and many symptoms of fragile X animals could be restored in animal models. This success led to the initiation of clinical trials, a “primeur” in neurodevelopmental disorders. A first trial on a selected group of patients showed a glimpse of hope for an improvement of some of the behavioral symptoms of patients, be it in a subgroup of patients only. Subsequent larger scale studies could not confirm the initial successes. In the chapter “The mGluR Theory of Fragile X: From Mice to Men” key investigators involved in the theory explain how they came to the theory and argue that, despite the initial disappointment of the clinical trials, the theory is as alive as when it was first described.
No neurodevelopmental disorder has faced more trials than the fragile X syndrome. Even for the investigators directly involved, it is difficult to keep track of all the clinical initiatives. The MIND Institute in Davis, California, and the Rush Medical Center in Chicago, Illinois, have been involved in almost all of these trials and needless to say there are no better authors to select for an overview of trials than the lead clinicians from these sites. The authors of this chapter “Overview of Targeted Double-Blind, Placebo-Controlled Clinical Trials in Fragile X Syndrome” present a dazzling overview of all of the targeted treatment initiatives following the identification of the drug targets as described elsewhere in this volume.
If you found this sample chapter interesting, you can access additional chapters online via ScienceDirect. If you prefer to purchase your personal print or e-copy, visit the Elsevier store. Apply discount code STC317 at checkout and receive up to 30% off the list price and free global shipping.
The scientific study of the nervous system is entering a new golden age. Researchers and clinicians continue to advance the treatment of conditions such as Alzheimer’s syndrome, Parkinson’s disease, epilepsy, and traumatic brain injury. Public initiatives like the federal Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) program in the United States, announced in April 2013, ensure that funding and resources will continue to be applied to this rapidly growing field. Elsevier’s journals, books, eBooks, online references, and tools are respected around the world for everything from physiology and pathology to behavioral genetics and nerve repair. Our publications are a gateway to the latest advancements in neuroscience research and leading-edge data for professionals, students, and academics alike.