I thank Borgolibero and Joan who introduce my project in this very important forum.
The idea born on my results on amino acid anaylisis in blood of epileptic pts: I found all large neutral amino acid (LNAAs) levels to be lower respect controls. Tryptophan (trp) is an LNAAs, it's the only precursor of brain serotonin, and its brain uptake rate depend on trp/LNAA plasmatic ratio. On my data I evaluated 1/3 reduction of trp brain uptake in epileptic pts respect controls. Recently, Chugani by PET demonstred that the brain serotonin synthesis depend on the aumount of trp uptaked in the brain.
To potentiate brain serotonin was wrongly believe to be pro-convulsant, in fact antidepressant SSRIs drug were reported to be pro-convulsants. In '90s our clinical results (Albano C) domenostred SSRIs are anticonvulsants, and in 2005 Jobe wrote tha at low doses, as used as antidpressant drugs, they are anticonvulsants, at higher doses, as used in experimental models, they are pro-convulsants. Jobe have a lot of experience on serotonin and epilepsy and in this paper reported a role of serotonin as brain controller, with the aim to keep isolated bad function neurons. If this controller system fail, these neurons are used in neuronal cyrcuits and epilepsy or depression come out, depending where are localized these bad function neurons.
The original idea was to increase trp/LNAA plasmatic ratio to increase trp brai uptake and brain serotonin synthesis.
starting '70s, a lot of papers reported good anticonvulsive response in animals by trp injections in blood, but clinical studies in humans with oral adminsitration carry out controversial results both in epilepsy and depression.
Gastroenterologic studies reported that free amino acids are not absorbed by intestine, they cross intestinal membrane thanks carrier systems and all LNAAs compete with the same carrier as at BBB. In spite of about 14 million of people using trp, i found only one paper on metabolic fate of trp in humans, but the authors had to inject in blood to see an increase in blood level!
In fact, gastroenerologic studies report that the best way to increase free amino acid plasma levels is by proteins, among them why protein carry out an higher increase, because they don't precipitate in acids of stomach and demolished to peptides freely cross the intestinal membrane.
Unfortnately all protein of our diet have a low trp/LNAA ratio, then they carry out a decreasing in this plasmatic ratio.
I found alpha-lactalbumin, a whey protein of milk, in human milk, too, it have a high trp/LNAA ratio and markus studies reported it able to increase trp/LNAA ratio in blood.
In 2006 started a open study on this protein in 18 drug resistant epileptic pts, the results were very good: 5 don't responder, 7 have an 50% of decreasing of seizures, 4 more of 80% and 2 go free from seizures.
After these results I contacted prof Perucca (Pavia, Italy) vice-president ILAE that help me a lot. Thank to Perucca, prof De Sarro, Catanzaro, tested ALAC on different experimental models, more than 500 animals, more than 1 year of study. These results were very good, also in pilocarpine model (ALAC is effective both in chronic and acute seizures of this model) and they let ALAC to entry in NIH screening tests as new drug.
The De Sarro's results confirmed the need to chronic administrations to have anticonvulsant effect. A single dose was not effective at any dosage, at least 5 days of repeated adminstrations were needed to have anticonvulsant effect, no dose depending in many experimental models.
On the basis of these evidences I start a new idea: to obtain an anticonvulsant effect is not enought increase trp/LNAA ratio, but it have to keep elevated for many days, in this way the neuroendocrine system carry out the stimulation of brain synthesis of neuropeptides, as NPY. Studies on NPY direcly injected in brain of animals showed an high anticonvulsant action, in fact it's named "endogenous anticonvulsant".
Neuroendocrine system link intestinal brain to brain, it's a control system and it give high and sudden response to prolonged stimuli. They are: fasting, as reported in Bible to control seizures, intesinal nutrients as fats, ketogenic diet, triglycerid, expecially medium chain T, the MCT diet, or trp and/or serotonin.
Then, SSRIs surely increase intestinal serotonin before reach brain, many AEDs increase trp and/or serotonin in intestine, and ALAC increase intesinal trp.
The new idea is about the possibility to act on intestine to promote brain synthesis of neuropeptides, as NPY, leptine, norephineprine. All of them are showed to be anticonvulsants and antidepressants.
The mechainsm of action of neuopeptides are different from those of neurotrasmitters, they act on neurogenesys and sinaptogenesys, in this way they make more easy to keep isolated the bad function neurons, in agrrement with Jobe's theory, making new neuronal circuitations in our brain.
It's my opinion more easy use endogenous system to control seizures, by gut-brain axes, than directly act on ionic channels of neurons. Moreover often we lost that any drugs when orally adminsiterd surely act on intestinal brain.
. Years ago , epileptic patients who also had depression had their depression lessened when they had seizures. That's why some brainiac decided to simulate seizures in non epileptic suicidally depressed patients - TADA! Electroconvulsive therapy. Now they're using this as a rationale for giving serotonin in epilepsy. Hmmmm. 
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