On Monday, Dr. Josh Schwartz came and spoke to our Nanoscience class about the development of preclinical cellular models of syndromic Autisms Spectrum Disorders (ASDs) in regards to nano-electrode arrays. Dr. Schwartz is from around my same hometown so it was interesting to see someone who came from the same place go and do different things. This was a very fascinating and dense in information talk so I will just be focusing on the things that I found especially interesting.
Perhaps the most interesting point was that a lot of the mutations in genes occur in synaptic genes. Synapses are where two nerve cells meet and are correlated to a lot of important developmental factors. In general psychology classes, one of the first things discussed is the anatomy of the brain: the different cortexes, the spinal cord, and neurons. One of the second things learned is how important neural health is especially in development. We learn how children who have less physical contact with their mother have poor myelin sheath development causing neurons to fire slower and have developmental and social delays. Synapses are the basis of communication neurologically and are of the utmost important. Therefore, they are incredibly sensitive to mutations. It truly makes a lot of sense that synaptic genes could be involved in autism which usually is hallmarked by social communication deficits. Dr. Schwartz talked about how mutations in syndromic ASD cases often disrupt synaptic biology and brain growth. If the synapses are not being formed, or are being formed incorrectly, the brain will not develop completely or correctly, leaving the patient with uncontrollable neurological challenges.
F. 1 Normal versus Fragile X chromosome in appearance
Fragile X syndrome is one of the most common genetic mutations associated with ASDs. Fragile X syndrome is caused by a mutation in the FRM1 gene which makes a protein necessary for synaptic plasticity. It was named fragile due to the appearance of its chromosomes under a microscope, shown above. The mutation is a CGG repeat, and the number of repeats controls the severity of the Fragile X. Because the FRM1 mutation has neurological impacts, one of the symptoms or the effects of the syndrome can be seizures. Dr. Schwartz discussed some therapeutic possibilities that researchers are experimenting with in order to "treat" the ASD. One of the issues with this is saying that an ASD is something that needs to be treated, however seizures are one symptom that would make an ASD enough to look for treatment. The main treatment discussed is amplifying the wild type or the "correct" version of the gene by blocking the miRNA from binding. miRNAs usually are inhibitory and repress protein synthesis, therefore by blocking the miRNA from binding, more protein is made. I have a few thoughts in regards to this with Fragile X. This syndrome mostly impacts males, they only need 1 copy of the mutation to have Fragile X syndrome. Additionally, they only have 1 copy of the FRM1 gene — they do not have a wild type that can be amplified. Thus, my thoughts are this: assuming that the FRM1 gene mutation was simply repressing the protein synthesis rather than making a wrong protein, the miRNA therapy could work. However, if the mutation makes the wrong protein, that therapy does not work, there is no correct protein to amplify. This goes to show the challenges of treating these syndromes, and the challenges of treating X linked diseases in males. Yet, I think there needs to be more work dealing with the ties to synaptic health and developmental delays, even with genetic causes. By identifying synaptic genes, and screening for carriers, I think potentially a lot of impactful work could be done. More so, looking at those synaptic genes and trying to find therapeutic solutions even to cope with the symptoms would help mitigate some of the challenges that patients face.
Works Cited:
“How Fragile X Syndrome Is Inherited.” Centers for Disease Control and Prevention, 3 June 2022, www.cdc.gov/ncbddd/fxs/inherited.html.
Sidorov, Michael S, et al. “Fragile X Mental Retardation Protein and Synaptic Plasticity - Molecular Brain.” BioMed Central, 8 Apr. 2013, molecularbrain.biomedcentral.com/articles/10.1186/1756-6606-6-15.
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