Parkinson’s Therapy- Part II

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Yesterday, we discussed the history of Parkinson’s disease and the initial attempts at treatments.  Ones that didn’t seem to provide more than short term relief for the patients.   Which is why research has continued- and new theories are being tested.

Now, we think that alpha-synuclein may be the cause of some actions that are critical to the development of Parkinson’s.  The synapse- the signal exchange points at the connections between neurons- has membranes that are controlled by this compound.   Too much of the protein and communication ceases, because dopamine transfer is blocked.  Oh, and these compounds are the chief ingredient of Lewy Bodies.   These are tiny clumps of proteins within the neurons that are associated with Parkinson’s.

Lewy Bodies

This alpha-synuclein scenario seems to be similar to ancient Greek theater.  The effects, the actions involved wuth this compound,  progress in three acts.   The alpha-synuclein forms sticky clumps (amyloids) that end up destroying the neurons- these neurons are the ones that produce dopamine.  The compound is first produced in the gut or the nasal cavities- some 2 decades before Parkinson’s symptoms are manifested.  These clumps are found in the neurons in Lewy bodies.  Once this point is reached, the patients manifest loss of smell, sleep disorders, and constipation.  (Yes, these are non-specific disease precursors for Parkinson’s.)

The second act involves the alpha-synuclein operating in the brain region of the substantia nigra.   Once 70% or so of the dopamine producing neurons are destroyed  (the Lewy Bodies are replete in the basal ganglia portion of the affected brains), symptoms are manifested by the patient. Then, the third act, when the disease includes the cerebral cortex, dementia and hallucinations are the norm.

As stated above, when the Lewy Bodies accumulate in the various portions of the brain, patients manifest loss of smell, sleep disorders, and constipation.   Once the Lewy Bodies are replete in the basal ganglia portion of our brains, Parkinson’s seems full blown.  When they are replete within the brain’s cortex, the patients manifest dementia.

Which is why research has now  been focused on reducing the levels of alpha-synuclein in the brain.   Many of the compounds that destroy alpha-synuclein also seem to have merit treating Huntington’s and Alzheimer’s, because the amyloids in those disease are related to the plaques found in those syndromes.   Neurophage Pharmaceuticals (Cambridge, MA) is working on these sorts of drugs.

Neurophage Pharmaceuticals

But, given the new data that our brain has a lymph system, it is possible that the lymphatic vessels are not able to keep up with the accumulation of Lewy bodies and alpha-synuclein in the brain.  Finding a way to activate the excretion pathway may also prove to be a useful long-term treatment.

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