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  "documentTitle": "Harmony Biosciences (HRMY)",
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      "text": "Altogether these data suggest that despite the increased number of HDC cells, extracellular histamine levels are likely normal in patients with narcolepsy.",
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      "text": "Scammell 2019 paper rejects histamine link; Histamine: neural circuits and new medications; Histamine Is Not a Reliable Biomarker for Narcolepsy and Other Central Hypersomnias",
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      "text": "...citing various studies showing no link to sleepiness; Histamine and tele-methylhistamine quantification in cerebrospinal fluid from narcoleptic subjects by liquid chromatography tandem mass spectrometry with precolumn derivatization",
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      "text": "furthermore, histamine levels did not correlate with subjective (Epworth Sleepiness Scale) and objective (Multiple Sleep Latency Test) measures of sleepiness or CSF orexin-A levels [85]. These results were in agreement with the normal cortical levels of tele-methyl histamine in orexin-/-mice compared with wild-type mice [20]. In a small number of patients with narcolepsy, CSF was collected again several months after the first sample; yet, histamine and tmHA levels showed no consistent change [86]. Altogether these data suggest that despite the increased number of HDC cells, extracellular histamine levels are likely normal in patients with narcolepsy.",
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      "text": "selective requirement to quantify these amines in human CSF. No significant difference was found in the mean±standard error levels of these amines between a group of narcoleptic patients (histamine=392±64pM, tele-methylhistamine=2431±461pM, n=7) and of neurological control subjects (histamine=402±72pM, tele-methylhistamine=2209±463pM, n=32).",
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      "text": "CEO Jeff Dayno has previously highlighted Thomas Scammell on a HRMY earnings call, a neurology professor and sleep expert at Harvard Medical School. Scammell wrote a paper in 2019 which summarized supportive studies that undermine the histamine hypothesis, beyond the 2012 Dauvilliers/Schwartz paper. For example, he cites another paper – on which Dauvilliers/Schwartz are ironically co-authors – that found no difference in histamine or T-meha levels between narcolepsy vs. control patients.",
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      "text": "Histamine Is Not a Reliable Biomarker for Narcolepsy and Other Central Hypersomnias — Thomas Scammell (2019 paper).",
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      "text": "Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335869/pdf/zsy183.pdf; https://www.sciencedirect.com/science/article/abs/pii/S0003269710006433?via%3Dihub",
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      "text": "We find it stunning that the lack of correlation between histamine levels and narcolepsy is an open secret in Harmony/Bioprojet’s inner circle of founders, trial investigators, and key scientific advisors.",
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