Research
At Stanford, the battle against SMA is in the Clinic and in the Lab.
Laboratory Research
Overview
Publications
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Overview
Currently in our laboratory, we are looking to achieve a greater understanding of Spinal Muscular Atrophy and also investigating potential therapeutic treatments for SMA.
First, we are looking specifically at the process of Survival of Motor Neuron (SMN) Protein production. So far we've already learned a great deal about the process. For example we know that in people without SMA, the SMN1 genes produce the majority of their SMN Protein. Because people with SMA lack both SMN1 genes copies, for them the process must start from the "back-up" SMN2 genes only. From only those, they must create SMN mRNA and then ultimately the protein itself. Unfortunately, more times than not this alternative version of the process results in a key piece of the protein getting left out, "exon 7." There has also been evidence to suggest that the more copies of the SMN2 gene a person with SMA has, the less severe their symptoms will be. There's still more to be discovered, however. We want to know exactly what is happening in these patients' cells and the precise reasons why they don't produce as much SMN Protein in the end as their non-SMA counterparts.
Second, we are also looking at how different molecules, Hydroxyurea for example, or groups of molecules may affect pieces of this process. Our lab is one of many throughout the US and globally working towards building a more complete picture of what is going on in the cells of people with SMA, with and without these extra molecules. Ultimately, of course, we all hope that this may bring us one step closer to being able to provide actual FDA-Approved treatments to our patients and help ease their suffering from this terrible disease.
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One project currently going on seeks to identify the actual mechanism by which Hydroxyurea may help increase the level of SMN protein in cultured cells. Additionally, as part of the Pilot Therapeutic Trial of Hydroxyurea on Spinal Muscular Atrophy here at Stanford, the SMA Research Laboratory is essential in determining the progression of certain efficacy biomarkers, namely the levels of SMN Protein and SMN mRNA. These could tell us how well the Hydroxyurea may be "working" on a cellular level. Once the studies are finished, we can compare this data with the clinical data from the study visits to see how well the two match up. We can also compare the effects of various doses and how they affect the protein and mRNA levels differently.
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Cultured motor neurons |
Publications
Grzeschik SM, Ganta M, Prior TW, Heavlin WD, and Wang CH. Hydroxyurea Enhances SMN2 Gene Expression in Sipnal Muscular Atrophy Cells. Ann Neurol. 2005 Aug;58(2): 194-202.
Gavrilov DK, Shi X, Das K, Gilliam TC, Wang CH. Differential SMN2 Expression Associated with SMA Severity. Nature Genetics. 1998;20: 230-231.
Yuan N, Wang CH, Trela A, Albanese CT. Laparoscopic Nissen Fundoplication During Gastrostomy Tube Placement and Noninvasive Ventilation May Improve Survival in Type I and Severe Type II Spinal Muscular Atrophy. J Child Neurol. 2007 Jun; 22(6):727-31.
For more information about SMA laboratory and clinical research, the PubMed Database has the most up-to-date publications and thousands of articles on SMA. Simply type in "Spinal Muscular Atrophy" on the main page and click "go."
