Lauren Elman, M.D., associate professor of neurology at the Hospital of the University of Pennsylvania and Penn Medicine, discusses her research with primary lateral sclerosis (PLS), a rare motor neuron disease often mistaken for ALS. #PrimaryLateralSclerosis #JohnsHopkins https://www.hopkinsmedicine.org/neurology_neurosurgery/clinical-trials/als-clinical-trials/
CHAPTERS:
2:15 PLS History
6:48 Natural History of PLS
14:31 Clinical Care in PLS
15:37 What’s needed to conduct PLS clinical trials?
18:06 Neuropathology of PLS
27:23 Consensus Diagnostic Criteria
35:32 Neurobiology of PLS
38:19 Genetics of PLS
39:03 Are ALS and PLS part of a spectrum of disease?
40:22 Biomarkers in PLS
43:34 Neuroimaging in PLS
47:24 Measuring PLS Progression
54:16 Clinical Trial Targets — Symptomatic
55:31 Clinical Trial Targets — Disease Modifying
1:03:20 Conclusion
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Concerning the etiology of PLS, are there studies of the possible role of the expansion of trinucleotide repeats in PLS?
Sometimes an inadvertent methylation of a cytosine in a CAG triplet, followed by spontaneous deamination of said cytosine, may transform it in thymine, producing then a stop codon ( TAG instead of the original CAG that codes for glutamine ).
Perhaps the inadvertent formation of stop codons could produce smaller peptides that could mimic nuclear localization signal peptides that would allow the intrusion of neuron nuclei. Ribosomal slippage events inside mitocondrial DNA should also be investigated as a possible source of instructions to produce peptides which, in the event of reaching the cell cytoplasm, might account for neuronal degeneration.