Sharry Edwards
Category: Sound Research

Identifying Triggers for Gluten Sensitivity

Identifying Triggers for GlutenSensitivity

Is it greed, ignorance or an attempt to make things better, thatis poisoning our population?

Find The Full Article At



The August 14th,2010 issue of Science News, reported that a research team, led bygastroenterologist Robert Anderson of the Walter and Eliza Hall Institute ofMedical Research in Parkville, Australia, had identified the triggers forceliac disease (gluten sensitivity).


Since the Sound HealthResearch Institute often evaluates clients who exhibit gluten sensitivity and amyriad of associated diseases, it was clear that this information needed to beadded to our databases. I decoded the three proteins as BioAcousticbio-frequencies (biomarkers) and was immediately involved in an avalanche ofnovel data.  The metabolic pathways distorted by these proteins aremultifaceted and link with nearly all systems of the human body; causing immunedistortion and acute cellular inflammation.


The article listed onlythree proteins, w-5 gliadin (wheat), g-3 hordein (barley) and g secalins (rye)that were responsible for the production of the specific anti-gliadin antibodyreactions.  These proteins, which were responsible for the allergicreactions, are associated with grain glutens from which they derive.


Patent records indicatedthe grains are clones developed in a laboratory by Monsanto.  This mayindicate that the present-day epidemic of gluten sensitivities/allergies stemfrom man-manipulated grains.  These gluten-containing, allergiccausing, grain clones are being used to create foods that we eat everyday; bread, cereals, crackers, pastry, seasonings, even some chips containwheat.  As I developed the BioAcoustic correlations I was aghast with therealization of how thoroughly our health is being negatively influenced bythese genetically modified foods. 


Further investigationrevealed that the cloned genes contained two substitutions that distorted theway the body processes two sulfur rich amino acids: proline andglutamine. This allergy creating substitutions result in thenon-methylation of these two amino acids. 


Glutamine distortionsseem to be the most destructive.  The enzyme required to utilize glutamineis glutamate decarboxylase (GAD).  Glutamate is a key molecule in cellularmetabolism and the most abundant excitatory neurotransmitter in the vertebratenervous system.

In mammals, GAD existsin two isoforms encoded by two different genes- GAD1 and GAD2 are expressed inthe brain where GABA is used as a neurotransmitter, GAD2 is also expressed inthe pancreas and has been associated with diabetes.


This led to anevaluation of the GAD genomes and what happens when these genes areactivated: 


Glutamate decarboxylase aka glutamic acid decarboxylase (GAD)is an enzyme that catalyzes the decarboxylation (part of the process ofbreaking down for use by the body) of glutamate to GABA (gamma aminobutyricacid) and CO2.


GABA is a naturaltranquilizer and an important inhibitory neurotransmitter that helps regulateneuron activity of the body’s nano sensors.  Starting with the GAD enzymeresponse and moving toward GABA along with the active form of B6, these Nanotransmitters of the body are created and regulated.  The movement ofelectrical energy and hence magnetic potential within the body are controlledby these Nano transmitters.


GAD uses PLP (pyridoxal50-phosphate) as a cofactor.  PLP was granted a patent by the USgovernment patent office to the Canadian company, Medicare.  PLP is nowunder the control of the pharmaceutical industry and is often associated withblood clotting issues, migraines, neural disorders and seizures.


Nano transmittersproduced in conjunction with GAD metabolism directly show associations withthese diseases: diabetes, autism, arthritis, Parkinson's, AL,S MultipleSclerosis, joint pain and deterioration, auditory disorders, Celiac Disease,Cohn’s, Irritable Bowel syndrome, diverticulitis, schizophrenia,  bipolarand anxiety disorders, aspartame sensitivity, MSG reactions, Lupus,Fibromyalgia, depression, seizures, brain signaling, the use of calcitonin(cancer related), histidine function (seasonal allergies), cellularinflammation and vaccination reactions.


Glutamate is an analoguefrequency of aspartame and is part of MSG (mono-sodium glutamate).  JamesOschman in his publication, Energy Medicine, states that cells emitfrequency based signals as a request for needed biochemicals to gather at thesite of the cell. Since Glutamate and Aspartame are the analog frequencies,this may explain why Aspartame has been implicated in so many muscle and jointdisorders.


These observations arebased on the mathematical matrix of biological BioAcoustics developed over thelast twenty years.  The system allows for the evaluation of itemsassociated with the body in terms of numeric Mathways.   I expectthis information will be the impetus that opens the world to the potential ofBioAcoustic Biology and the hope of allowing access to Self-Health care; evenafter the fact. 


Is it greed, ignoranceor an attempt to make things better, that is poisoning our population? Is Mathas Medicine our hope for the future?




July 2, 2017 -      AFTERTHOUGHT


Wheat has beenidentified as a major lectin (ANTINUTRIENT) that can cause significantdigestive upset. Humans are unable to digest lectins efficiently. *Researchshows lectins bind to cells on the gut wall causing a range of issues includingimmune dysfunction and inappropriate cell growth.


The lectins in wheat arephytohemagglutinins which cause the issues with the digestion of wheat. I’m wonderingif plant phytohemagglutinins that cause digestive lectinupset are the same or similar to the hemagglutinin added tovaccines since they both seem to cause the same issues.


NATHAN SEPPA.2010. Separating wheat from chaff in celiac disease. [ONLINE] Availableat: [Accessed 11 July 2017].

Alessio Fasano.2009. Celiac Disease Insights: Clues to Solving Autoimmunity Study of apotentially fatal food-triggered disease has uncovered a process that. [ONLINE]Available at: [Accessed 11 July 2017].

Editor. 2017. [ONLINE] Available at: [Accessed 11 July 2017].

Editor. 2017. [ONLINE] Available at: [Accessed 11 July 2017].

Alexandra Rowles, RD.2017. 6 Foods That Are High in Lectins. [ONLINE] Available at: [Accessed 11 July 2017].


SharryEdwards © 07/2017
























ReferencedArticle Abstracts




Quoted: “This pathway depicts the diverse metabolic fates androles that glutamate plays in the body. As seen from this diagram, glutamatecan serve as a precursor or substrate molecule for many compounds. Forinstance, glutamate can be generated from glutamine with the concomitantproduction of ammonia through the action of the enzyme glutaminase. Glutamatecan also be oxidatively deaminated through glutamate dehydrogenase to produce2-oxoglutarate and ammonia. Additionally, glutamate can be generated fromalanine or aspartate in combination with 2-oxoglutarate using the enzymetransaminase. The resulting byproducts (pyruvate and oxaloacetate) are keycomponents in glycolysis, gluconeogenesis and the TCA cycle. Glutamate andproline metabolism are also connected. In particular, 1-pyrroline-5-carboxylateis a biosynthetic metabolite that is synthesized from proline by the enzymepyrroline-5-carboxylate reductase and converted into the amino acid glutamateby the enzyme 1-pyrroline-5-carboxylate dehydrogenase. Glutamate also plays animportant role in the body’s disposal of excess nitrogen through the reactioncatalyzed by glutamate dehydrogenase, which converts glutamate and NADP into2-oxoglutarate, NADPH and ammonia. The ammonia is then excreted predominantlyas urea. Glutamate can also participate with glutamine and ATP in the synthesisof several other phosphorylated compounds such as carbamoyl phosphate,phosphoribosylamine and glucosamine 6-phosphate. These molecules can serve asprecursors for purine and polysaccharide metabolism. Another enzyme,glutamate-cysteine ligase (GCL), will conjugate glutamate and glycine withcysteine to produce glutathione, a key redox regulatory molecule in the cell.Glutamate also serves as the precursor for the synthesis of theneurotransmitter known as GABA (gamma-Aminobutyric acid) in GABA ergic neurons.This reaction is catalyzed by glutamate decarboxylase (GAD), which is mostabundant in the cerebellum and pancreas. Glutamate also serves as the mostabundant fast excitatory neurotransmitter in the mammalian nervous system. Atchemical synapses, glutamate is stored in vesicles. Nerve impulses triggerrelease of glutamate from the pre-synaptic cell. The glutamate then travelsacross the synapse, binding to glutamate sensitive receptors such as NMDAreceptors on the post-synaptic cell, activating the cell.” – end of quote

ScienceNews, August 14th, 2010; Vol. 178 #4 (P 8), Separating wheat from chaff inceliac disease.

GAD and Diabetes

The Diabetic Antigen Glutamic AcidDecarboxylase (GAD 65) in the Human Peripheral Blood

G.P. Tilza,b, J. Dausseta, M. Wiltgenc

InternationalArchives of Allergy and Immunology – Vol 152, No 2, 2010

Int ArchAllergy Immunol 2010; 152:184-194 (DOI: 10.1159/000265540)


Background: Glutamic acid decarboxylase (GAD 65) is adiabetes-associated antigen which is generally considered to be strictlyintracellular. In order to better understand autoimmunity, this studydemonstrates the appearance of GAD 65 in the peripheral human blood andpresents implications for the diagnosis and therapy of some autoimmunediseases. Methods: The GAD 65 molecules are detected by their interaction withmonoclonal antibodies labeled with dyes in an experimental setup withfluorescence correlation spectroscopy (FCS). These interactions result inchanges in Brownian motion measured as fluorescence fluctuations. Sera from 153patients with diabetes mellitus type 1 and controls were investigated. Toenable the representation of the molecule as a model for further discussions,we present structural visualizations of its hydrophobic properties, leading topossible interactions with the cell membrane lipids and epitope locations.Results: The GAD65 antigen could be measured with a sensitivity of 2.65 µg/mlin ‘clean systems’ resulting from spiking experiments and human sera. The GAD65 antigen could be identified in 8 patient sera: 4 children with diabetesmellitus type 1 and 4 adults initially taken as controls but whoretrospectively showed signs of autoimmunity. Conclusion: We conclude that thesefindings are of significance for the concept of autoimmunity, i.e. in aninitial step the immune system is primed by its accessibility to GAD 65. Ourexperimental results may also be important for the therapy of diabetes mellitustype 1 and other autoimmune diseases by the passive administration of GAD 65antibodies.

Copyright ©2009 S. Karger AG, Basel


GAD and Diabetes/Calcitonin:

GAD andCalcitonin - Calcitonin is a 32–amino-acid peptide with a ... Calcitonin is ahormone that participates in calcium and phosphorus metabolism.   BioAcoustically calcitonin is a major playerin the role of how the body handles cancer threat.

Immunohistochemicallystaining of alternate consecutive sections revealed numerous glutamate decarboxylase-likeimmunoreactive Purkinje cells that also contained calcitonin gene-relatedpeptide.

 It can be postulated that acetylcholine,?-aminobutyric acid, dopamine, calcitonin gene-related peptide, enkephalins anddynorphins (whose coexistence with choline acetyltransferase and enkephalinshas been previously described immunocytochemically) coexist in lateral efferentneurons.

Title: Diabetes mellitus decreases the expressionof calcitonin-gene related peptide, gamma-amino butyric acid and glutamic aciddecarboxylase in human pancreatic islet cells.

Al-Salam S,Hameed R, Parvez HS, Adeghate E.

Departmentof Pathology, Faculty of Medicine & Health Sciences, United Arab EmiratesUniversity, Al Ain, United Arab Emirates.


OBJECTIVES: The pattern of distribution ofcalcitonin-gene related peptide (CGRP), a neuropeptide, gamma-aminobutyric acid(GABA), a neurotransmitter and GABA-converting enzyme, glutamic aciddecarboxylase (GAD) in the pancreas of diabetic patients was investigated todetermine whether diabetes mellitus influences the expression of thesebiological transmitters.

METHODS: Pancreatic tissue samplesretrieved, during pancreatectomy, from cancer patients with and without Type 2diabetes were paraffin embedded. The expression of CGRP, GABA and GAD wasexamined in pancreatic tissue using immunofluorescence techniques.

RESULTS: CGRP, GABA and GAD were observed inmany cells located in the central as well as the peripheral regions ofpancreatic islet. The expression of CGRP, GABA and GAD decreased dramaticallyin pancreatic islet cells of diabetic patients compared to control. CGRP andGABA co-localized with glucagon in some pancreatic islet cells of both normaland diabetic patients. The pattern of distribution of CGRP, GABA and GAD innormal and Type 2 diabetic patients was similar to that of insulin.

CONCLUSION: The number of human pancreatic isletcells expressing CGRP, GABA and GAD decreased significantly after the onset ofType 2 diabetes. These neuropeptides and neurotransmitters may play a role inthe regulation of pancreatic beta cell function.

PMID:20010500 [PubMed - indexed for MEDLINE]

GAD and Autoimmune Diabetes

J DiabetesSci Technol. 2009 March; 3(2): 320–330.

Publishedonline 2009 March.

The Role ofImmunomodulation Therapy in Autoimmune Diabetes

Johnny Ludvigsson,M.D., Ph.D.

for theLinköping Diabetes Immune Intervention Study Group

Division ofPediatrics and Diabetes Research Centre, Department of Clinical andExperimental Medicine, Linköping University, Sweden

Correspondenceto: Johnny Ludvigsson, M.D., Ph.D., Department of Clinical and ExperimentalMedicine, Division of Pediatrics and Diabetes Research Centre, Faculty ofHealth Sciences, Linköping University, SE-581 85 Linköping, Sweden; emailaddress

Funding:These studies have been supported by the Swedish Research Council, the SwedishChild Diabetes Foundation (Barndiabetesfonden), the NovoNordisk Foundation, DiamondMedical, the Söderbergs Foundation, the County Council of Östergötland, and theRegional Research Fund of Southeast Sweden (FORSS).

Disclosure: DiamydMedical has sponsored the phase-2 trial on GAD (Diamyd) treatment and supportedthe mechanistic studies. There is no other connection to Diamyd Medical, andtherefore there exists total independence in research. I have in recent yearsalso had funding from NovoNordisk for studies on antibodies toward insulinanalogs and honoraria for lectures from NovoNordisk, Sanofi-Aventis, and EliLilly.


Type 1diabetes (T1DM) is characterized by loss of virtually all endogenous insulinsecretion. If residual insulin secretion is preserved, this will lead toimproved metabolic balance, less acute and late complications, improved qualityof life, and, in case of pronounced improvement of residual insulin secretion,complete remission and even cure of the disease.

Immunesuppression or immune modulation have been demonstrated as a proof of principleto stop/decrease the destructive process and thereby preserve beta-cellfunction. Several methods to save residual beta-cell function have been triedfor more than three decades with little or no evidence of efficacy. Positiveeffects have been seen mainly in adult patients but have been minimal or absentin children with diabetes. Furthermore, the safety of these immune interventionsand/or their benefit to risk relationships have not been found to justifyclinical use.

Morespecific immune modulation with anti-CD3 monoclonal antibodies has resulted inmore encouraging postponement of C-peptide decline, but with frequent and seriousadverse effects. Still more promising are the autoantigen therapies, of whichglutamic acid decarboxylase (GAD) vaccination has shown significantpreservation of residual insulin secretion in 10–18-year-old type 1 diabetespatients with recent onset. Efficacy was most impressive in the subgroup ofpatients with diabetes of short duration (<3 months). The treatment wassimple, well tolerated, and showed no treatment-related adverse events. Ifthese results can be confirmed, there is a realistic hope that GAD vaccination,perhaps in combination with vaccinations with other autoantigens and/or othertherapies, will result in remission for some patients. The prospects of cureand prevention of T1DM will become less remote.

Keywords:autoantigen treatment, C-peptide, glutamic acid decarboxylase vaccination,immune intervention, immunomodulation, type 1 diabetes

Physiol Res.2004;53(3):279-86.

Anti-GAD-positivepatients with type 1 diabetes mellitus have higher prevalence of autoimmunethyroiditis than anti-GAD-negative patients with type 1 and type 2 diabetesmellitus.

  H,Perusicová J, Hill M, Sterzl I, Vondra K, Masek Z.

ThirdDepartment of Medicine, General University Hospital, First Faculty of Medicine,Charles University, Prague, Czech Republic.


The aim ofour study was to evaluate antibodies against thyroglobulin (anti-TG) andthyroid peroxidase (anti-TPO) - markers of autoimmune thyroiditis - in severalgroups of adult patients with type 1 and type 2 diabetes mellitus (DM). We wereparticularly interested whether the presence of thyroid antibodies is relatedto the positivity of glutamic acid decarboxylase antibodies (anti-GAD). Wefound elevated anti-GAD in 46 % (97/210) patients with type 1 DM. All patientswith type 2 diabetes were anti-GAD-negative. At least one thyroid antibody(anti-TG and/or anti-TPO) was found in 30 % (62/210) patients with type 1 DMand 27 % (22/83) type 2 diabetes patients. The patients with type 1 DM werefurther grouped according to their anti-GAD status. The anti-GAD-positivepatients had a higher prevalence of anti-TG antibodies than theanti-GAD-negative patients (25 % vs. 12 %, p=0.03) as well as anti-TPOantibodies (32 % vs. 12 %, p<0.001). At least one thyroid antibody wasdetected in 39 % (38/97) of anti-GAD-positive but only in 21 % (24/113) ofanti-GAD-negative patients with type 1 DM (p=0.006). No significant differencein the frequency of thyroid antibodies was found between anti-GAD-negativepatients with type 1 and type 2 DM (21 % vs. 27 %, p=0.4). The groups with orwithout thyroid antibodies in both type 1 and type 2 diabetic patients did notdiffer in actual age, the age at diabetes onset, duration of diabetes, bodymass index or HbA1c level. Patients with elevated thyroid antibodies had significantlyhigher levels of TSH than those without thyroid antibodies (1.86 vs. 3.22mIU/l, p=0.04 in type 1 DM; 2.06 vs. 4.89 mIU/l, p=0.003 in type 2 DM). Weconclude that there is a higher frequency of thyroid-specific antibodies inanti-GAD-positive adult patients with type 1 DM than in anti-GAD-negativepatients or in patients with type 2 DM. Patients with or without thyroidantibodies do not differ in age, DM onset and duration, BMI or HbA1c. Thyroidantibodies-positive patients have higher levels of thyroid stimulating hormone(TSH).  PMID: 15209535 [PubMed - indexedfor MEDLINE]


GAD and Autism

 Acta Neuropathological

Volume 113,Number 5, 559-568, DOI: 10.1007/s00401-006-0176-3


Title: Decreased GAD67 mRNA levels incerebellar Purkinje cells in autism: pathophysiological implications

Jane Yip,Jean-Jacques Soghomonian and Gene J. Blatt


The recentidentification of decreased protein levels of glutamate decarboxylase (GAD) 65and 67 isoforms in the autistic cerebellar tissue raises the possibility thatabnormal regulation of GABA production in individual neurons may contribute tothe clinical features of autism. Reductions in Purkinje cell number have beenwidely reported in autism. It is not known whether the GAD changes also occurin Purkinje cells at the level of transcription. Using a novel approach, thepresent study quantified GAD67 mRNA, the most abundant isoform in Purkinjecells, using in situ hybridization in adult autistic and control cases. Theresults indicate that GAD67 mRNA level was reduced by 40% in the autistic group(P < 0.0001; two-tailed t test), suggesting that reduced Purkinje cell GABAinput to the cerebellar nuclei potentially disrupts cerebellar output to higherassociation cortices affecting motor and/or cognitive function. These findingsmay also contribute to the understanding of previous reports of alterations inthe GABAergic system in limbic and cerebro cortical areas contributing to amore widespread pathophysiology in autistic brains.


GAD and Multiple Sclerosis (MS) andAspartame

 The Connection Between MS and Aspartame

 By Russell L. Blaylock, MD



Recently, much controversy has surrounded a claim thataspartame may produce an MS-like syndrome. A current review of recentpeer-reviewed scientific studies has disclosed a pathophysiological mechanismto explain this connection. As far back as 1996 it was shown that the lesionsproduced in the myelin sheath of axons in cases of multiple sclerosis wererelated to excitatory receptors on the primary cells involved calledoligodendroglia. Recent studies have now confirmed what was suspected backthen. The loss of myelin sheath on the nerve fibers characteristic of thedisease is due to the death of these oligodendroglial cells at the site of thelesions (called plaques). Further, these studies have shown that the death ofthese important cells is as a result of excessive exposure to excitotoxins atthe site of the lesions.

Normally, most of these excitotoxins are secreted frommicroglial immune cells in the central nervous system. This not only destroysthese myelin-producing cells it also breaks down the blood-brain barrier (BBB),allowing excitotoxins in the blood stream to enter the site of damage.Aspartame contains the excitotoxin aspartate as 40% of its molecular structure.Numerous studies have shown that consuming aspartame can significantly elevatethe excitotoxin level in the blood. There is a common situation during whichthe excitotoxin exposure is even greater. When aspartate (as aspartame) iscombined in the diet with monosodium glutamate (MSG) blood levels are severalfolds higher than normal. With the BBB damaged, as in MS, these excitotoxinscan freely enter the site of injury, greatly magnifying the damage. So, we seethat dietary excitotoxins, such as aspartame and MSG, can greatly magnify thedamage produced in multiple sclerosis. Likewise, excitotoxins have been shownto break down the BBB as well.

Of equal concern is observation that we know that about 10%of the population (based on autopsy studies of elderly) have MS lesions withoutever developing the full-blown disease, a condition called benign MS. A diethigh in excitotoxins, such as aspartame, can convert this benign, subclinicalcondition into full-blown clinical MS. The amount of excitotoxins consumed inthe average American diet is considerable, as shown by several studies. Inaddition, the toxin methanol is also in the aspartame molecule. Methanol is anaxon poison. Combined toxicity of the aspartate and the methanol adds up toconsiderable brain toxicity and can convert benign, subclinical MS intofull-blown MS. Once the MS becomes full-blown, further consumption ofexcitotoxins magnifies the toxicity, increasing disability and death.

Recent studies have also shown that even single exposures tothese food-based excitotoxins can produce prolonged worsening of neurologicallesions. In addition, it has been demonstrated that autoimmune reactions (asoccur with MS) greatly magnify the toxicity of aspartate and glutamate (theexcitotoxins). We also know liquid forms of excitotoxins are significantly moretoxic because of rapid absorption and higher blood levels. In the face of thisconnection between excitotoxicity and the pathophysiology of MS, it would beludicrous to allow further use of this excitotoxin containing sweetener.



1.Sannchez-Gomez MV, Malute C. AMPA and kainate receptors each mediateexcitotoxicity in oligodendroglial cultures. Neurobiology of Disease 6:475-485,1999


2. YoshikaA, et al. Pathophysiology of oligodendroglial excitotoxicity, J NeuroscienceResearch 46: 427-437, 1996.


3. Singh P,et al. Prolonged glutamate excitotoxicity: effects on mitochondrialantioxidants and antioxidant enzymes. Molecular Cell Biochemistry 243: 139-145,2003.


4.Leuchtmann EA, et al. AMPA receptors are the major mediators of excitotoxindeath in mature oligodendrocytes. Neurobiology of Disease 14:336-348, 2003.


5. TakahashiJL, et al. Interleukin1 beta promotes oligodendrocyte death through glutamateexcitotoxicity. Annal Neurology 53: 588-595, 2003.


6. Pitt D,et al Glutamate uptake by oligodendrocytes: implications for excitotoxicity inmultiple sclerosis. Neurology 61: 1113-1120, 2003.


7. Soto A,et al. Excitotoxic insults to the optic nerve alter visual evoked potentials.Neuroscience 123: 441-449, 2004.


8. BlaylockRL. Interactions of cytokines, excitotoxins and reactive nitrogen and oxygenspecies in autism spectrum disorders. Journal of American NutraceuticalAssociation 6: 21-35, 2003.


9. BlaylockRL. Chronic microglial activation and excitotoxicity secondary to excessiveimmune stimulation: possible factors in Gulf War Syndrome and autism. JournalAmerican Physicians and Surgeons, Summer, 2004.



 Journal of the Neurological Sciences

Volume 47,Issue 3, September 1980, Pages 353-364

 Abnormal glutamic acid metabolism in multiplesclerosis are open

Westall CorrespondingAuthor Contact Information, a, b, Angela Hawkinsa, b, George W. Ellisona, b andLawrence W. Myersa, b

At the SalkInstitute, San Diego, CA U.S.A.

by theMultiple Sclerosis Research Clinic, Department of Neurology, UCLA School ofMedicine, Los Angeles, CA U.S.A.

Received 18February 1980;

accepted 16April 1980.

Availableonline 18 March 2003.


We havefound extensive amino acid abnormalities in multiple sclerosis sera. The mostconsistent abnormality is an elevation in serum glutamate, which is moststriking during relapses. The increase in glutamate in the patients does notoccur sharply during the onset of the relapse. Instead it appears to risegradually within a month or two prior to the onset of the clinical relapse, toreach a peak during the relapse and then to slowly decline.

This workwas supported by NIH grants NS-12391 and NS-08711.


GAD and Irritable Bowel Syndrome

Scand JGastroenterol. 2007 Nov;42(11):1289-93.

GAD and GutMotility

 Autoantibodies in patients with gut motility disordersand enteric neuropathy.

Törnblom H,Lang B, Clover L, Knowles CH, Vincent A, Lindberg G.

Karolinska Institute,Department of Medicine, Karolinska University Hospital, Huddinge, Stockholm,Sweden.


OBJECTIVE: Enteric neuropathy with mildinflammation (ganglionitis) has been described in several motility disordersincluding irritable bowel syndrome (IBS), enteric dysmotility (ED),slow-transit constipation (STC) and chronic intestinal pseudo-obstruction(CIPO). The purpose of this study was to test the hypothesis thatautoantibodies directed against specific neural antigens including ion channelsmay be associated with this finding.

MATERIAL AND METHODS: Comprehensive routine andimmunohistochemical analyses of full-thickness jejunal laparoscopic biopsieswere performed on patients fulfilling the international criteria for IBS, ED,STC and CIPO. Patients with ganglionitis had sera screened for specificantibodies to voltage-gated calcium channels (VGCCs) of P/Q- and N-type,voltage-gated potassium channels (VGKCs), glutamic acid decarboxylase (GAD) andneuronal alpha3-AChR by validated immunoprecipitation assays.

RESULTS: Thirty-three patients were includedin the study. Two of them, both with IBS, were found to have positive antibodytitres. One had anti-VGKC antibodies and one had anti-alpha3-AChR antibodies.No antibodies were detected in GAD or VGCCs (case reports presented).

CONCLUSIONS: A small proportion of patients withinflammatory enteric neuropathy have antibodies directed towards neuronal ionchannels. The pathogenic role of such antibodies requires determination but mayrepresent a possible aetiology of severe functional symptoms in these groups ofpatients.

PMID:17918010 [PubMed - indexed for MEDLINE]


GAD and Parkinson’s

European Neurology– Vol 12, No. 1, 1974Brain Glutamic Acid Decarboxylase Activity in Parkinson’sDisease

U.K. Rinne,H. Laaksonen, P. Riekkinen, V. Sonninen

Departmentof Neurology, University of Turku, Turku

Address ofCorresponding Author

Eur Neurol 1974;12:13-19 (DOI: 10.1159/000114599)

The activityof glutamic acid decarboxylase (GAD), the enzyme involved in formation of theinhibitory neurotransmitter ?-aminobutyric acid (GABA), was studied in autopsybrain samples from six parkinsonian patients and 13 controls. There wasrelatively good postmortem stability of GAD in deep-frozen brain samples over a3-week period. The activity of GAD was significantly reduced in brain samplesof patients with Parkinson’s disease, being about 50&percnt; of that incontrols. Moreover, levodopa treatment showed a tendency to increase theactivity of GAD. The results suggest the involvement of GABA neurons inParkinson’s disease.

Copyright ©1974 S. Karger AG, Basel


GAD and Parkinson’s/Epilepsy

Neurology.1971 Oct;21(10):1000-7.

Title: Glutamic acid decarboxylase inParkinson's disease and epilepsy.

McGeer PL,McGeer EG, Wada JA.

PMID:5165300 [PubMed - indexed for MEDLINE]


GAD and Aspartame

Eur J ClinNutr. 2008 Apr;62(4):451-62. Epub 2007 Aug 8.

GAD and Aspartame

Direct andindirect cellular effects of aspartame on the brain.

Humphries P,Pretorius E, Naudé H.

Departmentof Anatomy, University of Pretoria, Pretoria, Gauteng, South Africa.

Eur J ClinNutr. 2009 May;63(5):698-9; author reply 695-8.

Eur J ClinNutr. 2009 Aug;63(8):1044.


The use ofthe artificial sweetener, aspartame, has long been contemplated and studied byvarious researchers, and people are concerned about its negative effects.Aspartame is composed of phenylalanine (50%), aspartic acid (40%) and methanol(10%). Phenylalanine plays an important role in neurotransmitter regulation,whereas aspartic acid is also thought to play a role as an excitatoryneurotransmitter in the central nervous system. Glutamate, asparagines andglutamine are formed from their precursor, aspartic acid. Methanol, which forms10% of the broken-down product, is converted in the body to formate, which caneither be excreted or can give rise to formaldehyde, diketopiperazine (acarcinogen) and a number of other highly toxic derivatives. Previously, it hasbeen reported that consumption of aspartame could cause neurological and behavioraldisturbances in sensitive individuals. Headaches, insomnia and seizures arealso some of the neurological effects that have been encountered, and these maybe accredited to changes in regional brain concentrations of catecholamines,which include norepinephrine, epinephrine and dopamine. The aim of this studywas to discuss the direct and indirect cellular effects of aspartame on thebrain, and we propose that excessive aspartame ingestion might be involved inthe pathogenesis of certain mental disorders (DSM-IV-TR 2000) and also incompromised learning and emotional functioning.

PMID:17684524 [PubMed - indexed for MEDLINE]


Gad and Anxiety

MolPsychiatry. 2006 Aug;11(8):752-62. Epub 2006 May 23.

Title: Association between glutamicacid decarboxylase genes and anxiety disorders, major depression, andneuroticism.

Hettema JM,An SS, Neale MC, Bukszar J, van den Oord EJ, Kendler KS, Chen X.

Departmentof Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics,Virginia Commonwealth University, Richmond, VA 23298-0126,

Erratum in:

MolPsychiatry. 2006 Aug;11(8):794.


Abnormalitiesin the gamma-aminobutyric acid (GABA) neurotransmitter system have been notedin subjects with mood and anxiety disorders. Glutamic acid decarboxylase (GAD)enzymes synthesize GABA from glutamate, and, thus, are reasonable candidatesusceptibility genes for these conditions. In this study, we examined the GAD1and GAD2 genes for their association with genetic risk across a range ofinternalizing disorders. We used multivariate structural equation modeling toidentify common genetic risk factors for major depression, generalized anxietydisorder, panic disorder, agoraphobia, social phobia and neuroticism (N) in asample of 9270 adult subjects from the population-based Virginia Adult TwinStudy of Psychiatric and Substance Use Disorders. One member from each twinpair for whom DNA was available was selected as a case or control based onscoring at the extremes of the genetic factor extracted from the analysis. Theresulting sample of 589 cases and 539 controls was entered into a two-stageassociation study in which candidate loci were screened in stage 1, thepositive results of which were tested for replication in stage 2. Several ofthe six single-nucleotide polymorphisms tested in the GAD1 region demonstratedsignificant association in both stages, and a combined analysis in all 1128subjects indicated that they formed a common high-risk haplotype that wassignificantly over-represented in cases (P=0.003) with effect size OR=1.23. Outof 14 GAD2 markers screened in stage 1, only one met the threshold criteria forfollow-up in stage 2. This marker, plus three others that formed significanthaplotype combinations in stage 1, did not replicate their association with thephenotype in stage 2. Subject to confirmation in an independent sample, ourstudy suggests that variations in the GAD1 gene may contribute to individualdifferences in N and impact susceptibility across a range of anxiety disordersand major depression.


PMID:16718280 [PubMed - indexed for MEDLINE]


GAD and Arthritis

Ann RheumDis. 2008 Jul;67(7):1051-2.

Methotrexateand its effect on the anti-GAD titre in two patients with rheumatoid arthritisand diabetes mellitus.

van DeutekomAW, Nurmohamed MT, Peters MJ, van Eijk IC, Dijkmans BA, Hamann D, Heine RJ,Simsek S.

PMID:18556448 [PubMed - indexed for MEDLINE]

 GAD and Migraines

Migraine prevention by targeting glutamatereceptors?

When migraine strikes, because of severe pain, oftenaccompanied by nausea and sensitivity to light and sound, sufferers areeffectively disabled for up to 72 hours. Since they are forced to stop whatthey are doing until the pain and other symptoms subside, migraine causes asignificant loss in productivity at work and the personal lives of thoseaffected. Migraineurs especially the 25% of migraineurs who experience morethan three migraine attacks per month are looking to drug developers to providenew drugs to prevent migraine attacks before they start. In the U.S. alone,approximately 30 million people suffer from migraines and the cost to employershas been estimated at $13 billion annually in lost productivity. Currently,several types of drugs, like generic beta blockers, calcium channel blockers,tricyclic antidepressants and anti-epileptic drugs, some of which are usedoff-label, are given to prevent migraines. However, many patients have only apartial response to these products, many of which have troubling side effects.Nevertheless, many migraine patients use existing drugs, illustrating how badlynew drugs are needed.

Given therole of glutamate in the pathophysiology of migraine, the future of migraineprophylaxis, may lie in modulating one of the receptors in the glutamatesystem, mGluR5.

At theforthcoming annual meeting of the American Academy of Neurology in Seattle(April 25 May 2), Addex Pharmaceuticals (SIX: ADXN) will present Phase IIa dataon ADX10059, a negative mGluR5 allosteric modulator, which shows efficacy intreating acute migraine attacks and provides evidence that inhibition of thisglutamate receptor subtype could play a role in stopping migraine attacksbefore they start.

Preclinicalexperiments and small-scale studies in migraineurs with drugs like ketamine,which acts on glutamate signaling through NMDA receptors (functionally relatedto mGluR5) and the NMDA antagonist memantine.

Contact:Mike Sinclair



Source: Eurekalert


GAD and Epilepsy

Clinical andExperimental Medicine

Volume 3,Number 1, 32-36, DOI: 10.1007/s102380300013

Anticardiolipin,glutamic acid decarboxylase, and antinuclear antibodies in epileptic patients

A. Verrotti,R. Greco, E. Altobelli, G. Latini, G. Morgese and F. Chiarelli


To explorethe hypothesis that raised anticardiolipin antibodies, glutamic acid decarboxylase,and antinuclear antibodies may be associated with epilepsy and/orpharmacoresistance, we studied titers in 74 epileptic patients and 50 controls.Epileptic patients were divided into two groups according to their response toanticonvulsant therapy. Group I included 52 children (30 females and 22 maleswith a mean age ± SD of 7.0±2.4 years) suffering from different types ofepilepsy who were treated with various anticonvulsants. Group II included 22children (10 females and 12 males with a mean age of 6.2±3.6 years) sufferingfrom therapy resistant epilepsy. We found that the prevalence ofanticardiolipin antibodies was significantly higher in epileptic patients thanin controls, while there was no significant difference between patients who wereseizure free and those with uncontrolled epilepsy. No significant differencewas found in glutamic acid decarboxylase antibodies between epileptic childrenand controls, and between patients who were seizure free and those withuncontrolled epilepsy. A significant difference in the incidence of antinuclearantibodies was found between epileptic children and controls, while nodifference was found between well-controlled and drug-resistant epilepsy. Inconclusion, the prevalence of anticardiolipin and antinuclear antibodies washigher in patients with epilepsy than in controls. There was no significantdifference in serum glutamic acid decarboxylase antibodies between epilepticchildren and controls, and between patients who were seizure free and those withuncontrolled epilepsy.

Key wordsAnticardiolipin antibodies - Glutamic acid decarboxylase antibodies -Antinuclear antibodies - Epilepsy

Received: 10October 2002 / Accepted: 18 February 2003

Correspondenceto A. Verrotti


 Gad and Schizophrenia

Possible implicationof an inosine triphosphate metabolic error and glutamic acid decarboxylase inparanoid schizophrenia are open

Bernardo S.Vanderheidena, b

A EasternPennsylvania Psychiatric Institute, Henry Avenue and Abbottsford Road,Philadelphia, Pennsylvania, 19129 USA

Departmentof Psychiatry and Human Behavior, Jefferson Medical College, Philadelphia,Pennsylvania 19107 USA


A micromethod for the determination of l-glutamic acid decarboxylase activity isdescribed. It is based on the direct determination of radioactivity by liquidscintillation counting of paper strips containing the labeled products,following incubation of the enzyme with uniformly [14C] labeled substrate, andsubsequent separation of the products by high voltage paper electrophoresis.The method was used to determine the effect of ITP on brain glutamic acid decarboxylase.ITP was found to be inhibitory to the enzyme.


The abilityto synthetize ITP was demonstrated in cell-free extracts of the human braincortex and various regions of the cat brain.

Based onthese observations, and the fact that a significantly lower erythrocyte ITPpyrophosphohydrolase activity is found among paranoid schizophrenics, ahypothesis is presented linking ITP pyrophosphohydrolase deficiency to paranoidschizophrenia through an accumulation of ITP in brain and its inhibitory effecton glutamic acid decarboxylase.

star, openPreliminary reports of this work were presented at the XII Latin-AmericanCongress of Physiological Sciences, Bogotá, Colombia 1975, and at the 172ndAmerican Chemical Society National Meeting, San Francisco, Calif. 1976.

 Biochemical Medicine

Volume 21,Issue 1, February 1979, Pages 22-32


Gad and Allergies

Clinical& Experimental Allergy

Volume 40,Issue 5, pages 820–830, May 2010

Title: The role of interleukin-4Ra inthe induction of glutamic acid decarboxylase in airway epithelium followingacute house dust mite exposure

J. A.Hirota1,


D. Smith2,

B. Lipsky2,

R. Ellis1,

Y-Y. Xiang3,

W-Y. Lu3,

M. D. Inman1

Articlefirst published online: 12 MAR 2010


Background Asthma is a disease characterized byairway inflammation, remodeling and dysfunction. Airway inflammationcontributes to remodeling, a term that is used to describe structural changesincluding goblet cell metaplasia (GCM), matrix deposition, and smooth musclehyperplasia/hypertrophy. GCM has been implicated in asthma mortality bycontributing to mucus plugs and leading to asphyxiation. In animal models, thisprocess is highly dependent on IL-13. Recently, we have described anIL-13-dependent up-regulation of a GABAergic signaling system in airwayepithelium that contributes to GCM. The mechanism by which IL-13 up-regulatesGABA signaling in airway epithelium is unknown.

Objectives To test the hypothesis that IL-4Ra signalingis required for allergen induced up-regulation of GABAergic signaling and GCM.

Methods BALB/c mice were exposed to an acutehouse dust mite (HDM) protocol and received vehicle, anti-IL-4Ra-monoclonalantibody, or control antibody. Outcomes included airway responses to inhaledmethacholine (MCh), histology for eosinophilia and GCM, phosphorylated STAT6levels using immunohistochemistry and immunoblot, and glutamic aciddecarboxylase (GAD) 65/67 and GABAAß2/3 receptor subunit expression usingconfocal microscopy.

Results Acute HDM exposure resulted inincreased airway responses to MCh, lung eosinophilia, STAT6 phosphorylation,elevations in GAD65/67 and GABAAß2/3 receptor expression, and GCM that wereinhibited with anti-IL-4Ra-monoclonal treatment. Control antibody had noeffect.

Conclusion The IL-4Ra is required forallergen-induced up-regulation of a GABAergic system in airway epitheliumimplicated in GCM following acute HDM exposure.


 Gad andStiff Man’s Syndrome 

Archives ofNeurology – Vol 61, No 6, June 2004

Anti–GlutamicAcid Decarboxylase Antibodies in the Serum and Cerebrospinal Fluid of Patients withStiff-Person Syndrome

Correlation withClinical Severity

GoranRakocevic, MD; Raghavanpillai Raju, PhD; Marinos C. Dalakas, MD

Arch Neurol.2004; 61:902-904.






GAD and Lupus/Fibromyalgia

Lupus. 2005;14(6):486-8.

Gad and Lupus

Anti-glutamicacid decarboxylase antibodies in a patient with systemic lupus erythematosusand fibromyalgia symptoms

Taylor-GjevreRM, Gjevre JA.

Division ofRheumatology, Royal University Hospital, University of Saskatchewan, Saskatoon,SK, Canada.


We reportthe case of a 29-year old female nurse with a five-year history of systemiclupus erythematosus (SLE) involving multiple systems and on chronic prednisonetherapy. This patient has a coexisting diagnosis of fibromyalgia fulfilling ACRcriteria. A recent deterioration in her level of functioning in addition to aflare of her inflammatory disease led to further evaluation. During the courseof investigation an anti-glutamic acid decarboxylase antibody was found to bepresent and significantly elevated. A therapeutic trial of baclofen did resultin improvement of her subjective myalgias. We raise the possibility of anautoimmune contribution to myalgic symptoms in a portion of SLE patients.

PMID: 16038114[PubMed - indexed for MEDLINE]


Gad and ALS

Journal ofNeurological Sciences - Volume 250, Issue 1, Pages 124-132 (1 December 2006)

GABAA-receptor mRNA expression in the prefrontal and temporal cortex of ALSpatients

Susanne PetriCorresponding Author Information email address, Katja Kollewea, ClaudiaGrotheb, Akira Horic, Reinhard Denglera, Johannes Buflera, Klaus Krampfla

Received 9March 2006; received in revised form 4 August 2006; accepted 8 August 2006.


There isevidence that excitotoxic cell death is involved in the pathogenesis ofamyotrophic lateral sclerosis (ALS). Electrophysiological and histologicalstudies support the pathophysiological concept of an impaired inhibitory,namely GABAergic, control of the motoneurons in the cerebral cortex of ALSpatients. Recently, pathological, neuropsychological and functional imagingdata have challenged the view that ALS is a disorder restricted to the motorsystem. The aim of our study was to investigate the expression of the mostabundant GABAA-receptor subunit mRNAs and the GABA synthesizing enzyme glutamicacid decarboxylase (GAD) in the prefrontal, temporal, occipital and cerebellarcortex of ALS patients compared to tissue of control persons. We performed insitu hybridization histochemistry (ISH) on human post-mortem cortex sections ofALS patients (n=5) and age-matched controls with no history of neurologicaldisease (n=5).

In theprefrontal and temporal cortex of ALS patients, we detected significantlyreduced mRNA expression of the a1-subunit, while the GABA synthesizing enzymeglutamic acid decarboxylase (GAD) was significantly upregulated in theseregions. In the occipital and cerebellar cortex, we did not seedisease-specific differences of the mRNA expression of the investigated subunits.


Gad and Celiac

Frequency ofAutoantibodies in Celiac Disease

Celiac.com01/29/2010 - A team of researchers recently set out to compare levels ofglutamic acid decarboxylase antibody (anti-GAD), islet cell antibody (ICA),thyroperoxidase antibody (anti-TPO), thyroglobulin antibody (anti-TG), antinuclearantibodies (FANA), antibodies to double-stranded DNA (anti-ds DNA), antibody toSjögren syndrome A antigen (anti-SSA), antibody to Sjögren syndrome B antigen(anti-SSB), Smith antibody (anti-Sm), smooth muscle antibodies (ASMA), andantimitochondrial antibody liver-kidney microsome (AMA-LKM) in patients withceliac disease against healthy control subjects,  and autoimmune hypothyroid patients.

 The research team included Erkan Caglar,Serdal Ugurlu, Aliye Ozenoglu, Gunay Can, Pinar Kadioglu, and Ahmet Dobrucali.They are affiliated variously with Faith Sultan Mehmet Education and ResearchHospital, the Cerrahpasa Medical Faculty at the University of Istanbul, andOndokuz Mayis University in Samsun, Turkey. They studied a total of 31 patientswith celiac disease, 34 patients with autoimmune hypothyroidism and 29 healthysubjects.

The teamused immunofluorescence to assess anti-SSA, anti-SSB, anti-Sm, anti-ds DNA,anti-GAD, anti-TPO and anti-TG were studied by enzyme-Linked ImmunosorbentAssay (ELISA), and AMA-LKM, ASMA, ANA and ICA.

Researchersused retrospective analysis to assess clinical data and the results of freethyroxine-thyroid stimulating hormone (FT4-TSH). The team used SPSS ver. 13.0for data analysis, and the ?2 method for comparisons within groups.

They foundthat the frequency of anti-SSA, anti-SSB, anti-GAD, anti-Sm, anti-ds DNA,AMA-LKM, ASMA, ANA and ICA did not differ significantly between the groups.


They foundlevels of anti-TPO and anti-TG antibodies to be markedly higher (<0.001) inautoimmune hypothyroid patients as compared with other groups.

Previousstudies have shown an increased frequency of autoimmune diseases of othersystems in people with celiac disease. Autoimmune antibodies specific for other autoimmune diseases appeared nomore frequent in people with celiac disease.

Source: U.S.National Library of Medicine, National Institutes of Health

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