semagacestat fails to treat Alzheimer's

Yesterday, Gina Kolata in the NYT wrote that a large PHARMA is abandoning its drug semagacestat that decreases the production of amyloid in patients with Alzheimer's. IMHO I believe that this was a failed concept from the start.  Alll neurodegenerative diseases (multiple sclerosis, ALS, Huntington's, Parkinson's and many many more) occur when the central nervous system is stressed and reacts excessively. The answer for all these conditions is the same, rein in this excessive response. Treat these conditions at the source..I wrote this about Parkinson's years ago. I think PURSOR could work equally as well on other neurodegenerative disorders. It is at least worth a try.

Elsewhere, researchers at NIH have declared that mood altering drugs appear to partially protect the brain against neurodegenerative diseases  I am glad to see that mainstream medicine is coming around to this axiom.

All mood altering drugs influence the immune system (immunomodulate)

Mechanisms of Glucocorticoid Receptor Action in Noninflammatory and Inflammatory Cells

Glucocorticoids differ from serotonin. The latter suppresses the inflammatory response (T_h1 driven) but augments T_h2. Glucocorticoids suppress either or both responses. Therefore, if you wish to manage an immune condition, the use of PURSOR^TM is far more specific than using the GLU sledgehammer. This is an extremely well-written article and, therefore, deserves a Frank McLynn award.

"Glucocorticoids exert profound and diverse physiological effects on a wide range of cell types. Produced and released from the adrenal cortex in response to stress, levels of glucocorticoids are under the control of the hypothalamic–pituitary–adrenal axis.

Glucocorticoids participate in numerous physiological processes such as glucose homeostasis; protein, lipid, and carbohydrate metabolism; development; neuorobiology; and programmed cell death. Glucocorticoids exert potent immunosuppressive and anti-inflammatory actions in a cell type–specific manner largely through the interruption of cytokine-mediated pathways. These anti-inflammatory actions are also complemented by the ability of glucocorticoids to induce apoptosis in many cells including thymocytes, blood monocytes, and peripheral T cells.

As a class of drugs, glucocorticoids are among the most widely prescribed in the world for the treatment of immune and inflammatory diseases, including asthma, rheumatoid arthritis, ulcerative colitis, and allergic rhinitis. They are also a component of many chemotherapy regimens for the treatment of leukemias, lymphomas, and myelomas because of their role in the induction of apoptosis. However, long-term use of glucocorticoids has been limited by adverse side effects ranging from suppression of the hypothalamic–pituitary axis and growth retardation to osteoporosis, in addition to the development of glucocorticoid resistance. These undesired side effects of glucocorticoids are hypothesized to occur mainly through activation of gene transcription, whereas the beneficial anti-inflammatory effects of glucocorticoids involve mainly mechanisms of gene repression.

Understanding the molecular basis of glucocorticoid-induced side effects requires an understanding of their actions on homeostatic signaling processes in all cell types. In this review, we discuss the basic cellular and molecular signaling mechanisms of glucocorticoid action during noninflammatory and inflammatory situations."

Mechanisms of Glucocorticoid Receptor Action in Noninflammatory and Inflammatory Cells -- Necela and Cidlowski 1 (3): 239 -- Proceedings of the American Thoracic Society:

Why 5-HTP and the PURSOR Protocol May Improve Parkinson's Disease Rx

Summary

The inevitable progression of Parkinson’s Disease (PD) is unresponsive to treatment. Dopamine (DA) agonists may promote the underlying neurodegenerative process. Combined 5‑hydroxytryoptophan (5-HTP), the immediate precursor of serotonin (5-HT), and levodopa therapy should block DA induced PD progression because DA and 5­­-HT have countervailing actions in the immune system. While DA promotes inflammatory Th1 cytokines, neurotoxicity and neural apoptosis (programmed cell death), 5-HT promotes anti-inflammatory Th2 cytokines, acts as a neuroprotectant, and is antiapoptotic. Combined DA and 5-HT precursor therapy (PURSOR) with levodopa and 5-HTP suspensions titrated by taste, already associated with unprecedented partial remissions in another neurodegenerative disorder, amyotrophic lateral sclerosis, should markedly improve symptomatic Parkinson’s treatment, decrease the incidence of levodopa toxicity, and, by restoring Th1/Th2 balance and putatively decreasing QUIN induced excitatory neurotoxicity, alleviate or even halt the progression of PD.

Seven Reasons:

A.      The buccal mucosal route permits both precursors to pass through the blood-brain barrier directly without first passing through the general circulation. Since this markedly diminishes the decarboxylation of either precursor prior to its entering the CNS, carbidopa is no longer necessary.
B.       Maximum therapeutic levodopa doses to assuage nigrostriatal DA deficiency should now be realized promptly and safely. Prior to the proprietary PURSOR protocol, the responsible clinician, concerned that increasing the levodopa dose could at any time induce severe adverse effects, knowing that the only clinical endpoints were the onset of levodopa toxicity or PD clinical improvement, recognizing there was no procedure to ameliorate levodopa toxicity except the passage of time, increased levodopa dosage slowly and gingerly. One can assume that many a PD patient never achieves maximal levodopa intervention because of this understandable concern. The PURSOR protocol permits one to increase levodopa more acutely since the administration of 5-HTP reverses the toxic symptoms of levodopa excess
C.      The neurotoxicity associated with PD and increased by levodopa administration presumptively can be reversed by the increase of 5-HT, a glutamate antagonist and a neuroprotectant with the ability to diminish excessive QUIN toxicity and cellular apoptosis associated with hyperstimulation.
D.      The PURSOR protocol, by promoting CNS 5-HT levels, should decrease or ablate the Th1>Th2 imbalances associated with autoimmune disorders and suppress or halt the underlying neurodegenerative PD process.
E.       The unprecedented and rapid partial remissions noted by patients with ALS treated with the PURSOR protocol strongly suggests that 5-HT is modulating the EAA-associated neurotoxicity endemic in neurodegenerative disorders.
F.      Approximately 15% of DA treated PD patients develop obsessive/compulsive disorders. The addition of 5-HT to the regimen potentially ablates this as a problem.
G.       PD destroys both dopaminergic and serotoninergic cells. If for no other reason, the joint administration of both 5-HT and DA precursors makes empiric sense.

(Full text) More Formal Presentation