The following is based on the proposition that changes in motor neuron response occurs initially through Transient receptor Potential Ion Channels(TRPs). TRPs are the body's fdetector system. They control, temperature, pressure and toxic ingress and inflammation and immune response.
The problem with this proposition is that long term changes in cellular responses occur over time in response to the original activation of TRP. However there is also evidence from other Neurodegenerative diseases that modifying the TRP response significantly reduces symptoms.
Proposed Treatment fof SOD1 MND
The defective SOD1 allows a build up of Reactive Oxygen Species (ROS)in the Motor neurons which causes an ingress of Calcium ions into the cell that results in the death of Motor Neurons. Ideally treatment should involve correcting the misfolding of SOD1 so that it works properly to mop up ROS. However there is limited scientific evidence that this is possible. Heat shock proteins may well correct this misfolding and as the proposed approach increases heat shock proteins it might be possible to achieve this on a temporary basis (once treatment stops misfolding would reoccur).
Excess ROS in a cell opens an ion port TRPM2 which accelerates cell death by ingress of Calcium. As MND is caused by an excess of ROS this port needs to be closed. St Johns wart contains compounds that are Anti-oxidant and are capable of closing this port.
Resveritrol has been shown to prolong the life of mice in a mouse model of MND. It is a powerful anti-oxidant and has also been shown to increase heat shock proteins . It also blocks an ion port associated with neuron inflammation and ingress of Calcium.(TRPA1 Ion channel)
Ginger contains a number of components that have been shown to increase heat shock proteins and to desensitise an ion port associated with Inflammation(TRPV1 ion channel) and calcium ingress. It also reduces natural killer cells in the immune system associated with death of injured cells. Natural Killer cells are up regulated in MND.
TRPV 4 is up regulated in degenerative neuron diseases and cloves contain a compound capable of desensitising TRPV4 ion port. It is also capable along with ginger in reducing Natural Killer cells that are up regulated in MND and associated with bad progressive outcomes.
TRPM8 is a cold sensitive port that is associated with creating non-inflammatory immune response. It down regulating the immune system from an excitatory state to a healing state. Extract of Eucalyptus up regulates TRPM8 and down regulates TRPA1 and must be included.
By using a rub on product the idea is to keep the active ingredient isolated in Brain and Spinal Fluids. This should greatly limit side effects but not entirely as some leakage is possible.
Likely Side Effect
1. As TRPs are involved in thermo regulation down or up regulation of them can cause sensation of hot or cold and these can be quite strong.
2. TRPs regulate numerous biochemical pathways in the body. Take TRPM8 it is up regulated in Prostate cancer, this helps the cancer to avoid being killed by the immune system. All fruit and vegetables contain compound that effect the operation of TRPs hence the need for a good balanced diet to maintain health.
3. There are numerous ion ports activated in neuron inflammation that cause some of the cellular problems in disease and I have made the assumption that these are turned on by TRPs, this may not be the case even though the evidence points to this. Thus the treatment proposed may not work at all or be only partially successful and may take some time to reach full effect.
The scientific evidence points to this type of structured approach being likely to tick most of the boxes in MND and most neurodegenerative diseases.
TRP Channels in Neuronal and Glial Signal Transduction
Christian Harteneck and Kristina Leuner
Edited by Richard Williams, Alexander Fliigel and Wilhelm Just
Current Drug Targets, 2011, 12, 724-736
Properties and Therapeutic Potential of Transient Receptor Potential
Channels with Putative Roles in Adversity: Focus on TRPC5, TRPM2 and TRPA1
Modulation Of Oxidative Stress And Ca(b+) Mobilization Through Trpm2Channels In Rat Dorsal Root Ganglion Neuron By Hypericum Perforatum.
Resveratrol Improves Mitochondrial Function and Protects against Metabolic
Disease by Activating SIRT1 and PGC-1a
ntioxid Redox Signal. 2011 Sep 15; 15(6): 1549–1565.
Role of Reactive Oxygen Species and Redox in
Regulating the Function of Transient Receptor