Has the holy grail for Parkinson’s disease been found?

Will the horribly named SynuClean-D treat Parkinsonism?  Here is the structure described  verbally.  Start with pyridine.  In the 2 position put benzene with a nitrogroup in the meta position, position 3 on pyridine NO2, position 4 CF3, position 5 CN (is this trouble?) position 6 OH.  That’s it.  Being great chemists you can immediately see what it does.

Back up a bit.  One of the pathologic findings in parkinsonism in the 450,000 dopamine neurons we have in the pars compacta at birth, is the Lewy body, which is largely made of the alpha-synuclein protein.  This is thought to kill the neurons in some way (just which form of alpha-synuclein is the culprit is still under debate — the monomer, the tetramer etc. etc).  Even the actual conformation of the monomer is still under debate (intrinsically disordered) etc. etc.

The following paper [ Proc. Natl. Acad. Sci. vo. 115 pp. 10481 – 10486 ’18 ] claims that SynuClean-D inhibits alpha-synuclein aggregation, disrupts mature amyloid fibrils made from it, prevents fibril propagation and abolishes the degeneration of dopamine neurons in an animal model of Parkinsonism.  Wow ! ! !

Time for some replication — look at the disaster from Harvard Med School about cardiac stem cells, with 30+ papers retracted. https://www.nytimes.com/2018/10/15/health/piero-anversa-fraud-retractions.html.  Ghastly.

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Comments

  • John Wayne  On October 22, 2018 at 9:09 am

    No contemporary medicinal chemist would put forth a compound like that, but contemporary medicinal chemistry has not had much success with amyloid diseases. If it works, we will be better off.

    From the description, it sounds more like this compound is a fancy detergent than a typical therapeutic. That could be interesting.

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