Excessive levels of calcium mark brains of individuals with Autism

Writing in Molecular Psychiatry, L. Palmieri of the Laboratory of Biochemistry and Molecular Biology, Department of Pharmaco-Biology, University of Bari (Bari, IT) and colleagues reported the results of a small-n study of levels of metabolic transporters in the brain tissue of individuals with and without Autism. They compared the contents of samples from the brains of individuals with Autism and individual without Autism (matched on the bases of sex, age, and time after death that the samples were obtained). They found aspartate-glutamate carrier activity was increased by excessive calcium levels in brains of the Autistic individuals.

Note bene: Although the authors speculate about the potential for this finding to lead to therapies, they expressly warn against certain possible applications: “In particular, our findings in no way support the use of [calcium] chelation as a therapeutic approach in autism. [Calcium] chelation has not only been purported of benefit in few anecdotal reports and small-sized open trials, but also carries a substantial risk to produce hypocalcemia, resulting in recent deaths of autistic children.”

Autism is a severe developmental disorder, whose pathogenetic underpinnings are still largely unknown. Temporocortical gray matter from six matched patient–control pairs was used to perform post-mortem biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier (AGC), which participates in the aspartate/malate reduced nicotinamide adenine dinucleotide shuttle and is physiologically activated by calcium (Ca2+). AGC transport rates were significantly higher in tissue homogenates from all six patients, including those with no history of seizures and with normal electroencephalograms prior to death. This increase was consistently blunted by the Ca2+ chelator ethylene glycol tetraacetic acid; neocortical Ca2+ levels were significantly higher in all six patients; no difference in AGC transport rates was found in isolated mitochondria from patients and controls following removal of the Ca2+-containing postmitochondrial supernatant. Expression of AGC1, the predominant AGC isoform in brain, and cytochrome c oxidase activity were both increased in autistic patients, indicating an activation of mitochondrial metabolism. Furthermore, oxidized mitochondrial proteins were markedly increased in four of the six patients. Variants of the AGC1-encoding SLC25A12 gene were neither correlated with AGC activation nor associated with autism-spectrum disorders in 309 simplex and 17 multiplex families, whereas some unaffected siblings may carry a protective gene variant. Therefore, excessive Ca2+ levels are responsible for boosting AGC activity, mitochondrial metabolism and, to a more variable degree, oxidative stress in autistic brains. AGC and altered Ca2+ homeostasis play a key interactive role in the cascade of signaling events leading to autism: their modulation could provide new preventive and therapeutic strategies.

This study originally appeared online in 2008, but even before then, some researchers had speculated that certain forms of Autism may be caused by the chemicals responsible for regulation of neural development. For example, Krey and Dolmetsch (2007) suggested that “mutations of several voltage-gated and ligand-gated ion channels that regulate neuronal excitability and [calcium] signaling have been associated with [Autism Spectrum Disorders; ASDs]. In addition, [calcium]-regulated signaling proteins involved in synapse formation and dendritic growth have been implicated in ASDs.”

Palmieri, L., Papaleo, V., Porcelli, V., Scarcia, P., Gaita, L., Sacco, R.,… & Persico, A. M. (2010). Altered calcium homeostasis in autism-spectrum disorders: Evidence from biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier AGC1. Molecular Psychiatry, 15, 38–52; doi:10.1038/mp.2008.63

Krey, J. F., & Dolmetsch, R. E. (2007). Molecular mechanisms of autism: A possible role for Ca2+ signaling. Current Opinions Neurobiology, 17(1), 112-119.

5 Responses to “Excessive levels of calcium mark brains of individuals with Autism”


  • My name is David Summers of Murfreesboro, TN and I have had MS for 16 years. I am 37 years old and as of January 2012, was effectively an 8.0 on the EDSS scale. Originally RRMS, my disease progression had become SPMS (very progressive) within 4 years of onset. Normally anyone in my position and with my bleak diagnosis is limited to a short future, absolutely no quality of life and a painful end…possibly prior to my 40th birthday if the current progression of the disease continued (without the slightest hesitation or glimmer of hope, my Neurologist just told me: “ Prepare to deteriorate”). But after I heard about Dr. Zamboni’s ‘liberation therapy hypothesis’ in 2010, I began my search for the vein-widening therapy. This put me into a clinic in Duluth, Georgia where they were doing the liberation procedure. I received immediate positive results post-procedure…along with the surgeon’s warning that 50% of the MS patients who undergo the liberation therapy suffer a re-narrowing of the jugular veins within a year or so. Sure enough, within 3 months I knew that I was going to be among the unlucky 50%; all of the original improvements disappeared as I relapsed.

    I felt the only way forward was to get it done again, hopefully this time with more enduring results. But where would I go to get this done again and how would that be possible? If my neck veins restenosed after the first treatment, what was to prevent that from happening again…and again? I began to read the Internet blogs and forum chats placed on the many new CCSVI sites by MS patients about where to go and what their experiences were. In this respect, the Internet became a valuable educational tool for me. On several of the blogs, I discovered a New York clinic where they placed a stent during the procedure to keep the jugular veins open, and that positive results were being seen. Grimly, I also discovered that although rare, the prospect of death as a result of this procedure was also a risk. At least one person in a recent study had died when the stent migrated to his heart. But I was willing to put those thoughts and the risks aside. What did I really have to lose? I was dying a slow death. As long as someone was able to treat me there was a chance to hope, and I was down for it. But that wasn’t the main question I was asking myself.

    As my disease rapidly progressed and my disabilities became more overwhelming, the question I was asking myself was, was it too late for me? Although I was happy with the fact that my original liberation therapy had diminished most of the symptoms above my waist, I had to ask myself if getting stents was merely settling for a compromised improvement. Having had some success, if I had this done again, I wanted more! Don’t get me wrong, I think the liberation therapy is a miracle discovery from God. As soon as I had my first procedure my cog fog lifted, the vision in my right eye improved greatly, the numbness in both hands dissipated by a few degrees, my ability to taste food returned, my energy levels were ’off the charts’, and my sleep was so sweet. Also, because MS had robbed my body of the ability to regulate body temperature by sweating, I had not been able to handle the hot, humid Southern summers where I live, except to blast cold AC non-stop as a survival method during those sickly ‘dog days’. After the procedure this changed too. I knew it when deodorant suddenly became necessity for my personal hygiene once again!
    For more information please visit our site http://davidsmsstemcelljourney.blogspot.in/

  • But it ended by the 90-day point and I was right back where I started. Immediately following the procedure I had dreams of rising from the wheelchair I’d been confined to for ten years and walking like a real man; but even with the incredible improvements overall, it seemed that the only healing occurred above the waist. Perhaps I would just have to accept that even if I could improve to what the full extent of the liberation therapy would allow, I would always be in a wheelchair. While researching the New York clinic and other places, my parents and I came upon CCSVI Clinic through a Google search. We discovered that they are essentially a research clinic operating under an IRB but with a major difference. For the past year, having seen even better results than just doing the liberation therapy alone, they have also been transplanting adult autologous stem cells, cultured and re-injected into the body shortly after the neck venoplasty. If I chose to go there instead of New York, the procedure would be done at CCSVI Clinic at Noble Hospital in Pune India and I would have to get there essentially as a partially paralyzed patient transported in a wheelchair. There would also be a requirement to stay in the hospital for 10-12 days. But after researching the improvements demonstrated in MS patients in stem cell clinical trials, I simply decided that as long as they would take me, nothing was going to stop me from making that trip. On calls with the clinic, it was also explained that stents were not necessary as the stem cells injected intravenously could be enough to keep my veins from restenosing. My confidence in their method increased when I discovered that Dr. Gupte, the neurosurgeon, had been transplanting autologous stem cells for 4 years for a number of different neurodegenerative conditions, including MS and based his therapies on completed stem cell trial methods done in a number of hospitals and universities outside of the US (to be absolutely sure, I confirmed this through searches on Google Scholar). He had already done over 2000 successful transplants! Regarding my communications with CCSVI Clinic, I need to confess here that we did not tell the doctors the truth originally. My mother, who arranged the treatments, told them that I was an EDSS 6.5 in order to qualify. Basically she knew that they wouldn’t accept me into the program if she said I was higher. But if they saw my actual physical condition could they refuse me on the clinic steps? I hoped not.

    So in late March it was off to India with my father who is a strong man, and my capable assistant. We arrived on March 26, 2012, and met Surjo Banerjee, CCSVI Clinic’s Managing Director at the airport. He drove us from the airport to Pune, a surprisingly modern city just south of Mumbai. I was amazed to see that the hospital and the CCSVI Clinic itself, (a full wing of suites within the hospital complex) was as clean and modern as any hospital here in the States. After checking in with a number of other patients, I was triaged for the procedures. However, based on my new assessment, it was determined that I would need about twice the amount of stem cells that they had originally programmed, figuring my EDSS scale requirement of 6.5. But paying more was out of the question. We are not rich and had basically ‘sold the farm’ to get here in the first place, and the recommended additional stem cells were going to cost another $12,000 that we had not planned for. Not their fault…I didn’t tell them the extent of my condition in the first place. So the first miracle happened when CCSVI Clinic management offered to personally cover these additional costs. I had never even met some of them, but as a result of their generosity, I received an additional 50,000,000 mesenchymal stem cells and I cannot thank them enough for the difference they have made to my life.For more information visit our site http://davidsmsstemcelljourney.blogspot.in/

  • Four days later I underwent a lower lumbar puncture, but this time not simply to gather information on whether I have MS. This time, stem cells cultured from my own body were on their way to do what God designed them to do, and that is to heal. For all of you that might be skeptical about this, I am here to tell you that is exactly what they are doing. The positive changes were noticed as soon as I returned to my suite in the clinic and anyone who is paralysed below the waist will understand this next part. To manoeuvre myself as I usually do, I went to pick my leg up from a sitting position and throw it in front of me. The hope here is that the ‘dead-weight’ of the leg will land just right and in a position where I can best situate myself to haul my body into a position where I can further awkwardly throw my whole body into my wheelchair. If you’ve ever seen a spinal patient do this or are unlucky enough to have to do this yourself, you know what an ugly, uncomfortable process this is. But this time the ‘throw’ of the leg proved to be an over-compensation. To my absolute shock and delight my leg lifted itself just as it’s supposed to work…without aid from my helpful hands and placed itself exactly where my brain told it go! At first I didn’t think much of it…this was a fluke, maybe my imagination, but it was something sure not to last. But it has to this day without any hint of regression as I work out and get stronger. This was the first sign of any recovery whatsoever that has occurred below the waist in over ten years, and it happened only hours after the stem cell transplant!

    Upon returning home on April 14, 2012, I closely followed the Clinic’s physiotherapy program. Since then I have been working out at levels I had been told by my doctors here in the states would not be possible again. When exercising before I had stem cell therapy, I always had to be careful not to overdo it because I would get a sickness that sometimes lasted 2 days, completely wiping me out. This even occurred after the first liberation therapy, but no more. I’ve been working myself silly and have not yet felt sick. Real strength has returned and muscles have been popping out in places on my body where I haven’t seen them in many years. As of this writing today, and for about the last two weeks my right hand has been functioning normally in every respect. I’m not saying it has improved some, I’m saying it is now completely NORMAL! I can hardly believe it myself.For more information visit our site http://davidsmsstemcelljourney.blogspot.in/

  • Since I returned, and after only one month, the positive changes have been happening regularly and most every day. Most significantly, I think, my incontinence has completely improved and I am now able to almost totally control my urinary and elimination functions. All other disabilities aside, I think that this is one of the most important deficits that anyone with MS wishes they could get back! Incontinence is so embarrassing and not having control of that particular function somehow makes you feel lesser as a person. So I’m very happy to see the improvements there. My speech is back to normal. Although I never slurred my words, the thought process was oh-so-slow. Now my words come so quickly that I sometimes find myself stumbling over them…trying to say too much at once. I can’t complain about that!

    I am convinced that CCSVI Clinic is on to important discoveries about MS. They have figured this out and are doing the sequence of therapies correctly and the addition of the stem cells completes the need to repair the nerve damage that’s been done by the disease. In retrospect what they are doing suddenly makes complete sense to me. It’s still early yet and I guess time will tell to what extent my motor functions will come back, but if the last month is any indication, it could be everything, which excites me so much. I don’t know if that’s too much to hope for, but it’s the first time in 10 years that I’ve even really allowed the thought to cross my mind. The first fleeting thoughts of this after the original liberation therapy 2 years ago weren’t realistic. The good changes didn’t last. And consider this; a few months ago, I was in a wheelchair, in a permanent brain fog losing more of my independence and quality of life on a daily basis. All I had to look forward to was a deteriorating condition where others would have to take care of my every bodily function. Now I can’t wait to wake up every morning to check myself out. If anything I’m too impatient and working out too hard. But at least I can! Given my current state of health and ability to live and function on my own, the thing that is very certain is that I have a much better quality of life back and that wouldn’t have even been possible if it hadn’t been for the lucky discovery of CCSVI Clinic through an Internet search. My family and I will be eternally grateful for what has happened no matter how this turns out. Thanks to Dr. Gupte, the other doctors, the medical team and staff at the Clinic who made this all happen for me, I’m looking forward to each day with new health and optimism! May God Bless them all!For more information visit our site http://davidsmsstemcelljourney.blogspot.in/

  • I have a long way to go, but as long as my jugular veins are wide open and the stem cells continue to clean up the mess those narrowed veins left behind, and damaged nerves continue to regenerate, I believe the sky is truly the limit! My main focus at this point is not only to rebuild muscle but to get my legs to work together, which will restore my balance.

    Every day is a new gift that allows me more recovery. I can hardly wait for each morning to see the next improvement! There’s so much more happening in my body than I’ve even mentioned in this writing but I hope I’ve related the main message here…MS was my previous diagnosis.

    I will be starting a blog on my progress in a week or two if anyone wants to contact me or follow my improvement. I’m sure there are many of you out there who are skeptical or would want to know how this is going for me. I’ll post the site information back here once I have it up.For more information visit our site http://davidsmsstemcelljourney.blogspot.in/

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