Neuroinflammation and Neurodegenerative Diseases: One Condition One Therapy

Does neuroinflammation fan the flame in neurodegenerative diseases?:

Microglial activation is the response to multiple traumatic insults whether triggered by infection, trauma or hypoxia. This common stress response can become self-feeding and can become chronic. The authors postulate that the particular presentation (PD, ALS, Huntingtons, etc) depends on genetic variation of environmental variability.

I believe and have so believed for more than a decade that all these conditions can be remitted by blocking the perpetuation of microglial activation by the use of dopamine and seotonin precursor therapy (PURSOR).

Summary

It is becoming increasingly evident that neuroinflammation plays a crucial role in the development and progression of many neurodegenerative diseases. Glia and in particular microglia are central to mediating the effects of neuroinflammation. While neuroinflammation and microglia provide an attractive therapeutic target in the treatment and prevention of neurodegenerative diseases investigators face several challenges ahead (Appendix 2) which must be overcome before one can advocate in favor of large-scale anti-inflammatory trials in the clinic. Some of these include developing approaches to improve the access of drugs to CNS tissue as well as developing therapies that maintain or optimize the beneficial effects of neuroinflammation while eliminating or minimizing its detrimental effects.

Key Observations

1. Neurodegenerative diseases are associated with signs of chronic neuroinflammation
2. A variety of initiating triggers (some as yet unknown) associated with the different neurodegenerative disorders converge at a common intersection point - activation of microglia.
3. While the initial neuroimmune response may be aimed at limiting the disease process, chronic neuroinflammation driven by persistent microglia activation is likely to aid in the progression of the disease and the hastening of neuronal demise.
4. How the inflammatory response affects specific neuronal and glial populations and contributes to specific neurodegenerative diseases remains a critical and unanswered question

Critical challenges involved in developing neuroprotective anti-inflammatory therapeutic strategies

1. Identify internal and external factors that trigger chronic neuroinflammatory responses, with a focus on how acute immune responses become chronic.
2. Identify inflammatory mediators that compromise survival of specific neuronal populations.
3. Develop therapeutic compounds that cross the blood brain barrier (BBB)
4. Selectively target destructive inflammatory mediators without compromising beneficial survival-promoting effects and overall immune function.
5. Develop inclusion and exclusion criteria for human subjects to be enrolled in clinical trials taking into account their immune status."

Lyme Arthritis: Current Concepts and a Change in Paradigm

The ability of B. burgdorferi, the spirochete responsible for Lyme Arthritis, to avoid clearance by the immune system may be attributed in part to an inadequate innate immune response upon infection. However, innate cells such as monocytes, macrophages, and dendritic cells display a vigorous response against borrelial infection and play a major role in the activation of the adaptive immune response against the spirochete. Despite these efforts, though, arthritis still develops in a significant number of patients infected with B. burgdorferi. It appears that the robust response elicited by monocytes, macrophages, and dendritic cells against the spirochete may be viewed as insufficient in early infection but excessive in the later stages. Paradoxically, in mounting such a strong defense against the organism, these cells may inadvertently be contributing to the induction of Lyme arthritis.

Lyme disease is associated with a chronic inflammatory bias with excessive T helper 1 cytokines. This condition has responded to PURSOR therapy in a Rhode Island lady who had not responded to antibiotic treatment at Yale under the care of my medical school classmate Allen Steere who has deservedly earned a reputation in this field.

Lyme Arthritis: Current Concepts and a Change in Paradigm

A Wide Specrum of Maladies are Associated with Immune Imbalance

I have a strong belief that the PURSOR protocol can correct the basic imbalance in both the innate and adaptive immune systems. I have compiled a list of just some of the many conditions whose symptoms and signs are directly associated with this imbalance. You can find at this site a new type of bibliography that I have created at the National Library of Medicine. One can retrieve all the references and then select whether you wish to select all the review articles or those articles with free full texts

Many investigators have postulated that were we to correct this underlying imbalance, commonly referred to as biased Th1/Th2 cytokine dysregulation, the chance of a remission would be likely I offer here two relevant and well-written articles. Moss, R.B. et al (2004) and Lucey, Clerici, & Shearer (1996).