[Sciences/Junk Sciences] Remember the deadly turmeric IV infusion done in a holistic clinic? Lessons from the FDA report

You have remember this story of this young woman that died shortly after recieving an IV infusion of turmeric acid (aka curcumin, a bioactive compound found in Curcuma) in a holistic clinic in California few months ago (http://www.10news.com/news/team-10/encinitas-woman-dead-after-i-v-infusion-of-turmeric).
This story baffled me for many reasons. First, it was really puzzling me on how quack medicine (rebranding itself as “holistic” and “integrative” to appear more sciencey) have been moving slowly but surely into medical procedures normally held by medical staff, with some dubious claims of “IV therapy” in which the onset of an IV line and pumping up vitamins straight into your systemic circulation will help you “detox” or “rejunevate”.
Second, how turmeric acid that have been bounced by some “health/food gurus” as superfood (move on kale and quinoa, you are so 2015!) quickly moved on as therapeutics without even having the right science to back it up (until now only preclinical studies done in cells grown on Petri dishes and in rodents), with the glittery “cures-it-all” sticker all over it.
You see, turmeric acid is way far from being the next wonder drug as sold by woo peddlers. Why? Lets see some of its features (https://pubchem.ncbi.nlm.nih.gov/compound/curcumin#section=Top).
First thing, turmeric acid has a problem. A huge problem. This problem is solubility. It has a calculated xLogP of 3.2, this is already telling us this compounds is lipophilic (likes fat). It will dissolve well in oil, but not well in water (less than 0.1mg/mL according to Santa Cruz Biotechnology data sheet). If you try to go beyond that value, you will have a saturated solution with turmeric acid precipitates. These precipitates can have serious effect if injected into an IV line, if these particles are big enough to clog some capillaries.
You can circumvent things around by tweaking nanoparticles carriers. Still, even from food intake, turmeric has a very low bioavailability. From 100g of pure turmeric acid swallowed, only 1g will effectively reach the circulation and circulate through your body.
The second problem with turmeric is its pharmacokinetic profile. According to the reference cited by the FDA report, turmeric is highly unstable at physiological pH (7.4). According to this review, the elimination half-life (t1/2) for turmeric is very low (1.7+/-0.5h). By 6 hours, most of the turmeric injected via IV route will be gone. Therefore, if turmeric was considering for therapeutic, it would require multiple dosing that are either ridiculous (Dosing interval of about ~2 hours, therefore swallowing a pill every two hours) or being on a constant IV infusion (that is not realistic for everyday life).
Third problem with turmeric? Its pharmacological activity. Two important parameters have to be accounted for a drug candidate: its selectivity (does the drug targets one or several proteins?) and IC50 (what is the concentration needed to achieve 50% inhibition).
The problem with turmeric is that it is considered as a “dirty” molecule because it hits a bit of everything, with many signaling pathways affected by it. The second problem is its very high IC50. Anti-cancerous activity of turmeric swings around 10microM in various cancer cell lines in a Petri dish and have other targets at higher doses. This is not a horrible value, not a good value either. Usually we want to reach an IC50 in the nanoM range (10’000 less concentration than 10µM). Thats not the case for turmeric. Maybe by tweaking the chemical structure we may improve its IC50, but since the compound itself has so many targets trying to optimize it for therapeutic purposes maybe simply a waste of time.
If we stick to the 10µM concentration and an average molecular weight of 328g.mol-1 for turmeric, we need a concentration of 3mg/L or (0.003mg/mL) to expect some biological activity. Now the problems come in with the FDA report. There are two reported cases of adverse events, including the fatal cases. In both cases, patient had an IV line of turmeric acid. In both cases, both patients were mentioned an IV infusion of turmeric acid at 10mg/mL. First, this concentration would have made no sense. It is 300 times higher than the hypothetical dose needed to achieve a biological activity in vivo. Second, the final concentration in the IV bag was much less than this concentration, as the FDA reported only 1% of the prescribed concentration was found in the IV bag (0.00235mg/mL).
Someone has been not only been deceiving their customers by selling you less product than advertised (1% net content is honestly a huge rip-off) but also had absolutely no clues on what they were injecting. So we can blame two actors: either the compounding company that prepared the turmeric or the holistic clinic (I guess you can point who is the crook in the story).
Both cases involved ImprimisRX, a compounding pharmacy. These are laboratories under the responsibility of a pharmacist holding a specialization in compounding. He or she has to follow established rules and protocols, adhere to good manufacturing procedures in compliance with the FDA. It seems there is no wrongdoing from the compounding. The compounding produced an emulsified form of turmeric (to increase its solubility). Yet, the final concentration in the vial was about 0.205mg/mL or about 2% of the amount put on the label. Since turmeric is highly unstable under aqueous solution (even in its emulsified form) we cannot exclude a degradation of the product from the time it got compounded to the time it was administered. In aqueous protein-free solution, 90% of turmeric acid is degraded within 30 minutes (https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PharmacyCompoundingAdvisoryCommittee/UCM466380.pdf).
Now comes an another problem: was there any deception between ImprimisRX and the holistic clinic? One of the reason is the use of polyethylene glycol 40 (PEG40) castor oil in the compounding process. PEG40 may contain traces of diethylene glycol (DEG), a very well known toxic compound if ingested, with a toxicity of about 1mg/kg. DEG is a byproduct of PEG production, therefore the FDA has different quality grades of PEG whether it is destined for non-medical usage or for human consumption. DEG was found at a concentration of 0.21% (0.21g pure DEG in 100g of PEG40). The PEG40 used for the compounding was 1.25% with the clear label “CAUTION: For manufacturing or laboratory use only.” Why the compounding pharmacy used that ungraded PEG40? We don’t know yet.
PEG40 oils are used for cosmetics and considered safe for cosmetics usage  because the bioavailability of this compound is small and suited for topical application (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505343/). But you have to remember that a product that is considered safe in an administration mode is not in another administration route. This is probably explaining the adverse effect observed.
The second possible issues is a possible allergic reaction to PEG40, as the FDA cited previous reports of allergic reactions of patients exposed to PEG formulations following IV infusion of anti-cancerous agents.
By now, your enthusiasm for cur turmeric should (rightly) wind down. Turmeric is certainly great for spicing your food, not much for your health. But most of all, don’t let a “holistic clinic” perform any type of IV infusion.
IV infusion is a very delicate procedure, used for restricted applications (chemotherapy, anesthesia, infectious disease……) by a trained personnel in a medical environment (hospital or medical clinic).

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[Music/Gothic Metal] Seven Spires – Solveig (80%)

Fresh from the press, a band that came out of nowhere in my disc library: Seven Spires, a FFM band from Boston, Massachusetts. Their first album “Solveig” was released this Friday and of course it ends up being reviewed by me. I have been listening several times, interrupted by the livestream of “Wacken Open Air 2017” (thats very nice from the organizers to have a livestream of the main line-up).
This is a 15-track album, lasting 75 minutes. iTunes classified it as death metal/black metal and fairly I disagree with it. Because this album does not fit in one category. It is definitely metal but explores different facets with some gothic, some symphonic, some even sounding like some black symphonic a la “Dimmu Borgir”. So yes, it is a very schizophrenic album but it also a kind of a good showcase for Adrienne Cowan, allowing her to hear her vocal range from clean to growls.
We get into “The Siren” an introduction that really sounds like a Danny Elfman track, you know something like straight from a gothic ambience of a “Nightmare Before Christmas”. It seamlessly brings to “Encounter” blending this Elfman tunes with heavy riffs. Good stuff, really gives you a good grip on the ride. Some fresh air, it has a been a while we did not hear a good gothic metal band and Seven Spires is kind of baiting with that appeal. Then we move to “The Siren (Reprise)” that rather sounds like a revisited opening sequence for “Encounter”. I found it odd to have right in the third track, I would have put as a bonus track. The fourth “Cabaret of Dreams”, sounds a bit more rock giving this kind of abruptness in the ride. Certainly not my favorite. “Choices” sets the train back on its track, brining on some symphonic elements with a heavier tone. A very engaging song that should have been in my opinion right after “Encounter”. “Closure” continues into this very enjoying emotional riding experience, with a slower tone supported by orchestral arrangements and maybe an annoying presence of the bass guitar. Thats one thing I noted, the presence of the bass was too much accentuated in this album. I know the bass player has bad rep but the bass is part of the background unless you are Iron Maiden or Lemmy Kilmister. “100 days” is this nice melodic ballad giving a nice interlude in the album, right in the middle of the album. “Stay” brings us a power melodic tone that is very engaging, a good one. “The Paradox” brings us for the first time Adrienne on the growls into this track that brings on the excitement of a symphonic black metal straight out of a good “Dimmu Borgir” album. You know this kind of track that put your auditive and limbic cortices into fritz, with this rush of dopamine that wants to mosh into your living room by this brutal riffs blended with awesome melodics. Oh yeah! Thats my favorite! This is kind of a title that tells you this band with the right direction that breaks some charts. “Serenity” is falling into more conventional genres, even sounding like metal core. “Depths” brings us back to calmer tracks, a nice one, something similar to the chords of Alissa or Vicky style encountered in “The Agonist”. “Distant Lights” brings on the melodic power metal. Nice but nothing that impressed me. “Burn”, brings on back this “Dimmu Borgir” feels with a good spoon of power metal, sending again into a rollercoaster ride from Hell.  “Ashes” brings on this what I call “anime metal”. Dont ask me why, but this is the kind of metal that would match very well with a opening sequence of an anime. Nice! “Reflections” brings back the orchestral sounding like a ending sequence.
The overall album is good, pretty good. But it kind of misses the overall excitement that some other albums have sparked in the previous months. Maybe it is this mix of different styles and some questionable tracks. Sometimes, lesser is better.
However, this album is a great showcase of Adrienne’s vocal range and ability to sing both in clean and growls. The band also have shown its comfort in playing in different styles with ease. But lets be honest, Seven Spires enters a market highly competitive, especially if they think to take the Symphonic metal direction. Right now, melodic death and power metal are very good niches for entering FFMs. Really, their black symphonic metal composition of “The Paradox” and “Burn” really felt taking a rollercoaster from Hell, giving the thrills and chills of an adrenaline rush only to kick in the endorphins at the end of the ride, sending you in this musical euphoria.

[Metal/Melodic Death] Exalt The Throne Last Show @ Dallas, TX (O’Rileys Bar – 07/29/2017)

We are born, we live and we die. Some people call it the circle of life. I don’t, i prefer the allusion of the thread of life metaphorized by the Ancient Greek through as the Moirai (or Fates) Clotho, Lachesis and Atropos. We exist as a thread with our beginning and our end. We cease to exist with the continuum but we remains as part of the fabric (history).
Same applies for our intellectual endeavors, scientific and artistic alike.
I have seen bands being born bringing the joy and the excitement with their innocence and novelty. I have bands that have been following me through my life, becoming a sort of travel companions through my own journey. Sadly, I also have seen bands giving their last breath and close their eyes.
The announcement of a band going into hiatus or disbanding is always a sad news to hear because you know that you will not experience anymore that auditory and visual stimuli that made them listen and like their work, over and over.
One of the band that lately gave their final curtain, their “barroud d’honneur” was Exalt The Throne (Dallas, TX). I discovered the band very recently as their supported Epica second leg North American Tour following the release of “The Quantum Enigma”. It was love at first sight because of this very interesting blend of melodic death (with high-paced guitars of Charles, Tim and Kanyon and drums) with symphonic metal (clean female vocals performed by Courtney). It was neither the former nor the latter. It was its own blend that made them unique. When the band announced their final show a month ago, it was unexpected and a very sad moment to experience.
However, I decided to drive all the way to attend their final show and have a chance to collect a last souvenir from the band. The gig was short but oh boy you could feel how the band matured over the last 18 months, refining their performance.  The band played three of their songs present in their album “Long Live the King” (“Long Live The King”; “Perpetual Agony” and “Rampant Idolatry”) and one cover from Amon Amarth (I ain’t fan of folk metal but if someone can help identify the song, I would be more than happy to update this post).

If I have to find a silver lining into this final show, I would definitely cite the first law of thermodynamics that stipulates “energy is not created nor destroyed in a closed system, it is only transformed and transferred”. Same applies to the artistic energy. It is only transformed and transferred. I wish to the band members all the best and success in their endeavors and in their personal and professional careers. The king is dead! Long live the king!

 

[Neurosciences/Cancer] About Sen. McCain brain tumor……and glioblastoma multiforme

You may have heard the tragic news that broke hell under the feet of Senator McCain (R-AZ) and his family on Wednesday. According to several sources, Senator McCain biopsy taken from his recent medical examination revealed to be classified as “glioblastoma multiform” (or GBM) for short.
I am not a brain cancer specialist but I have been doing some collaboration with a research group focused on GBM and I know all too well what does it mean and what is the prognosis. This is a type of tumor I would not wish my fiercest archenemy to get. I thought it would maybe help me to make a lay summary on GBM and explain why the BBB in that case is one of our fiercest challenge for drug delivery.

1. What is glioblastoma multiforme?
Glioblastoma multiforme (aka GBM) is a primary brain tumor characterized by its heterogeneity. However, we assume that GBM is originating from tumor astrocytes. Astrocytes are an important cell type of the macroglia, outnumbering neurons from 3:1 to 5:1. For a long time, astrocytes were considered as “glue cells”, playing only a function of scaffold and nourishing cells to neurons.
However, in the last 50 years, astrocytes have been shown to play much more important roles including the induction of the blood-brain barrier phenotype, regulation of the cerebral blood flow, modulation of neuronal cell activity, ability to form a parallel signaling network and also to play an important function in terms of protection of the brain during diseases.
The World Health Organization (WHO) classify GBM as a grade IV brain tumor (https://link.springer.com/article/10.1007/s00401-016-1545-1), meaning this type of cancer is classify as highly aggressive. Because the brain is a very soft tissue, tumor cells can easily proliferate, migrate and invade the surrounding healthy tissues.
The cause of GBM remains unclear, however we know that some GBMs are evolved from other types of brain tumors that have a lesser malignancy like lower-grade astrocytomas (grade II) or anaplastic astrocytomas (grade III). GBM is considered the most common type of primary tumor (not caused by metastatic cells) but also remains pretty rare with a case of 2-3 new patients diagnosed with the condition for every 100’000 inhabitants. There is a possible sexual dimorphism, as men are more likely to be affected than women (3:2 ratio), with an increased risk with age (https://www.ncbi.nlm.nih.gov/pubmed/17373878).
There is no particular risk factor associated with GBM. So far, we assume it has a strong genetic background, as several genes have been associated with GBM including some abnormalities (including loss of DNA in a chromosome domain) on the chromosome 10, mutations in various genes including TP53 (tumor suppressor gene, its function is to repair cell DNA or to induce cell death by apoptosis if it fails to repair), MDM2 (pro-survival gene, its function is to promote cell survival), EFGR and PDGFRα (these are two receptors that induce cell growth, cell proliferation and cell survival upon stimulation by growth factors).
Also noteworthy, there has been speculation and a perpetuated myth that wireless cell phones activity are associated with an increased risk of developing brain tumors. There is no reliable studies (both on epidemiological standpoint and on animal models) that can show an association between the use of cell phones with increased risk of brain tumors.

2. What are the treatments and prognosis for patients with GBMs?

This is where I cannot have much optimism. GBM is a very aggressive type of cancer. The average survival rate is about 18 months, with less than 5% of patients making through the 5-year milestone.
Like any type of cancer, there are different options proposed: radiation therapy, surgery and chemotherapy.
Surgery is commonly practiced but have several challenges: Firstly, it is very hard to identify GBM tissue from the healthy tissue by naked eye during surgery. The neurosurgeon has to rely on the MRI cliches to resect the tumor tissue. Secondly, the neurosurgeon wants to maximize the removal of tumor tissue but also he/she wants to limit the damage to the surrounding healthy tissue to not induce further brain damage. Thirdly, GBM is prone to form glioblastoma stem cell-like cells (GSCs) that share several features with stem cells. These cells can tolerate very aggressive environment and can rapidly proliferate. This is one of the common complication occurring in GBM patients. After you remove the tumor and see no trace of it under the MRI, you conclude it got eliminated. Only to find out three months later that the tumor grew back in size and started to invade more brain tissues.
Chemotherapy arsenal for GBM is very limited. So far, temozolomide is the way to go for GBM. However, 50% of the patients will not respond to temozolomide due to a mutation in the MGMT gene capable to inactivate it (http://www.sciencedirect.com/science/article/pii/S2352304216300162). Other anti cancerous agents including EGFR inhibitors (e.g. lapatinib) fail to show any activity to the presence of a pathological form of the blood-brain barrier (BBB) called “brain-tumor barrier” (BTB). This abnormal form of the BBB involve interactions with brain tumor cells. For a long time, the scientific community thought that BBB surrounding brain tumors was leaky and therefore accessible to chemotherapeutics. However, we know that indeed there is a BTB that can act as a barrier for the penetration and delivery of drugs into the tumor region.

There are some new avenues and approaches to target GBM but they are still very experimental. Amongst them, the possibility to use oncolytic viruses like a modified form of the polio virus capable to set brain tumor cells into “auto-destruction” mode. The second avenue explored is possible use of immunotherapy. The rationale behind is to help the immune system “to learn” about the tumor cells as foreign agents and strike them. There are some success using antibodies targeting tumors and also by reprogramming patients own cells (CAR-T cell therapy).

The diagnosis of GBM is probably one of the most difficult one a neurologist or neurosurgeon has to set, as it has a very poor prognosis. Let’s be honest, it is not looking good and for someone like Senator McCain that has been facing death several times during his military duties this is probably the toughest one to overcome.

3. Concluding remarks

This is why we need to foster research in brain tumors, this is why we need funding to help research findings, this is why we need clinical trials to pick the most promising drug candidate to fight this type of cancer, this is why we need to have a public health policy that ensure healthcare coverage for everyone can have access to treatment to beat the odds and not have to decline treatment because of the huge costs associated that health insurance may simply refuse to share the burden.

I am so embarrassed to say that right now the only thing we can provide Senator McCain and anyone with GBM and their relatives are our sympathies and our wishful thinking. This is why I have colleagues, peers working days and nights, weekends to bring on a “silver bullet” capable to annihilate such condition.

If you are looking to help, the best I can advise is to support research by donating to association like ABTA (http://www.abta.org) that focuses on funding research on brain tumors. Also considerate to let your voice heard and support healthcare policies that ensure an universal coverage of the population regardless of their age, gender, socio-economic status. Because refusing treatment by fear of letting your most loved ones with a humongous amount of debt should be the last of your worry.

 

 

 

 

 

 

[Movies/Horror] George A. Romero (1940-2017)

Today, one of the masters of horror left us alone. Indeed, horde of zombies and living dead are orphan tonight. George A. Romero left us today at the age of 77.

What can I tell about Romero? He is the father of the zombies as we know it. All the zombies (not the infected ones like 28 days later) have in my opinion to follow the Romero’s canon: originated from an infectious agent, resulting in their transformation into creature solely driven by their reptilian brain and nourishing from flesh-eating.

But beyond the living dead image, Romero was indeed a very talented filmmaker, because the zombies, the living dead, were indeed us, a mirror image reflecting on our society.
Romero’s genius resided in his ability to shock and awe the viewer, but only to ask them to think about the symbolism and the meaning. Through the tetrad of the “Living Dead” (Night/Dawn/Day and Land), Romero was behind his movies stinging us in the heart of the society.

“Night” was indirectly bringing on the table the case of Vietnam war veterans and the racism that was still alive and kicking 100 years after the Civil War and just a couple of years after the Civil Rights Movement. Romero shook the American audience by having Duane Jones, an African-American, as one main character. This was a very bold and progressive move from Romero, but also a very provocative one. Jones was the hero, he was the one that set a barricade, where the “white savior complex” got slashed through the entire movie. The white man is coward, hide from the danger and will kill any non-white on sight. Duane Jones performance was fantastic and at the end of the movie *SPOILER ALERT* survived the whole living dead siege only to be shot from distance by a sheriff *SPOILER ALERT*.

“Dawn” was set about 10 years later than “Night” and at another period, another criticism of our society. That time, a virulent prosecution of the consumer society. It starts with the siege within a TV station in which the channel director fulminates on how the usual programming grid is interrupted in a middle of a major chaos. When we end with “Night”, we have this false sense that the situation is under control, that it was just some isolated incident. “Dawn” shows the gravity of the situation. Big cities are in total chaos, SWAT teams with National Guards and some enthusiastic drunken gun-totting civilians try to keep the situation in order. We see the society crumbling before our eyes, with law and order of the civil society sinking into abyss. The only refuge of all this chaos is…..a shopping mall. A f***ing shopping mall with living dead wandering around, as a reflection of their past lives. Again, another African-American takes the lead impersonated by Ken Foree. Where all people of the survival group lost themselves into their delusion, Ken stood still and focused and again one of the only one to survive, with an open-ending that keeps us with a question unanswered: with an helicopter running out of fuel and the two last survivors flying over in the horizon, did they make it safe or did they just die?
The contribution of Dario Argento resulted in two major directors cut, with my favorite is of course the Argento cut.

“Day” is again set 10 years later and again Romero’s use to fingerpointing at his best. The US is now invaded by living dead, only small pockets of resistance are maintaining their survival. This group ironically found refuge in a former ICBM silo. This one goes heavily on the US military, with the absurdity of the military in pursuing insane research, just look at Bubba experiment, such absurdity culminates at the end of the movie and only those that kept their ethics straight.

“Land” was certainly one that was the most misunderstood. It got half-bombed in the box office but was indeed one of the most visionary version 20 years early. A divided US, between those surviving in junk towns and the only happy few (a clear illustration of what we call “The 1%”) living literary in their ivory tower in a delusional world, dreaming of their “Make America Great Again” promised by the ruling class on the pleb, with pleb dreaming that one day they will also belong to that 1%.

George A Romero also had other movies that encountered much a mitigated success but George also acquired the highly distinguished title of “Master of Horror” with his collaboration on “Creepshow” with Stephen King.

Tonight, one Master of Horror gave us his latest salute. May your soul rest in peace and let your filmography haunt us with your spirit 😦

[Neurosciences/BBB] 8th GLUT1 Deficiency Conference – Summary

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Today wrapped the second and last day of the 8th GLUT1 Deficiency conference that was held in Nashville, TN this year. It was my second time I am attending this conference and honored to be a guest speaker this year.

 

The whole conference took place at the Inn at Opryland, part of the Gaylord Resort at Opryland. It is a fairly impressive complex with shuttle to the Opry Mills outlet shopping center and, the Gaylord Resort & Convention Center (in which the AACP is also holding a meeting starting today but I am just attending one day meeting there).

According to the organizers, we had about 220 attendees, with 68 families present. What I liked this year was the blending between parents, healthcare providers and scientists. In the previous conference, the first day was family and healthcare providers and the second day was the professional day. This allowed a unique interactions, questions & answers and discussion.

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It was also a very good time for updating my knowledge on the disease. Not much on the basic science, but more on the current treatment and dietary intervention with various experts of the field including Pr. Jorg Klepper (University of Essen, Germany); Pr. Juan Pascual (UT Southwestern, Dallas, TX); Pr. Eric Kossoff (John Hopkins University, Baltimore, MD) and other scientific experts.
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My learning from the conference is that the disease in an evolutive disorder. We learn more about the disease as we learn from the patients growing in. As the patient grows, he or she displays different symptoms: “funny eyes movements” during infancy, presence of absence seizures during toddler times and learning attention and deficit during early school age, presence of movement disorders in both during childhood and adulthood and migraines, hemiplegia and “writers hand fatigue” syndrome. This seems to be linked by an impaired glucose uptake in the cerebral cortex and the thalamus.  It also seems that there is at some point in the disease the presence of a sexual dimorphism, as female patients seems to experience in their teenage years a “paroxysmal dystonia” that seems triggered by moderate and vigorous exercise. So, the GLUT1DS is not a static disorder. It is a disorder evolving over time with its clinical manifestations evolving as well.
The second thing I learned is the variety of “ketogenic diets”. There is not one single “keto diet” but several variants with different dosages and variety, including a Modified Atkins Diet.

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It seems there is not a “one size fits all” but rather different types of diets that also seems to vary with age.

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The younger age appears to need the following of a strict keto diet and as the patients age, some softening and flexibility can be introduced. It seems the critical time for the keto diet is infancy and childhood. The earlier the child is introduced, the better. There are also several companies providing cookbooks, supplements like keto powders or kets-friendly products aimed for patients.

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In terms of diagnosis, some interesting news came from a French biotech startup that can measure GLUT1 levels in RBC within 24 hours using a proprietary cell assay (that looks like an antibody assay) using a flow cytometry-based approach.
Another interesting result is the outcome of the ketogenic diet for GLUT1DS patients. For the vast majority of GLUT1DS patients (95% of patients), the keno diet significantly decrease the number of seizures by at least 50%. In contrast, other types of epilepsies combined only show a 50% of patients showing a responsive outcome to keto diet. Still, 5% of GLUT1DS do not respond to keto diet and there is a fraction of patients that show a normal glucose CSF levels and/or GLUT1 expression. We certainly have a lot of patients that undergo undiagnosed or misdiagnosed for years as “drug-refractory epilepsies”. But it seems that some patients maybe falsely diagnosed as GLUT1DS. Hopefully, with the decrease in price for DNA testing (it seems 23andMe can detect some GLUT1 SNPs) may help to broaden the diagnosis and identification of patients.
Some interesting topics presented at the conference was some possible drug adverse effects reported in G1D heterozygous mice in particular to diazepam and phenobarbital but also other drugs. Some parents noted the anecdotical adverse reactions following certain treatment. However, the absence of studies directly investigating such drug adverse effects in G1D patients most of the time go under the radar, with the health practitioner attributing it to the disease condition rather than some particular drug adverse effects. Having from screening tools can greatly help.
Another interesting presentation is the study of G1D heterozygous mice. These mice seems to display a lower brain vascular density compared to wild-type. This is not surprising considering the recent work of Pr. Peter Carmeliet (Universidaed Leuwen, Belgium) on endothelial cell metabolism. According to Pr. Carmeliet, brain endothelial cells highly depend on glycolysis to function despite being in presence of plenty amount of oxygen levels.
There have been also discussion of trying to setup a comprehensive guide for parents for a consensus on GLUT1DS diagnosis and management that can help them as a source for documentation during their visit with their doctors. There is also a discussion of improving the community outreach to professionals and politicians to improve the funding and the recognition of GLUT1DS as a condition, discussing about supporting open-access options for certain papers allowing parents a free-access to these new studies and also finding ways to support GLUT1DS awareness and management among minority populations and in other geographic areas (especially South America).
The person missing at this meeting by his presence was certainly Pr. Daryl DeVivo (Columbia University, New York, NY). Little patients left him some very kind words and their name on a paper board. I found it was a very cute gesture and remembered us that his absence was felt.
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The interesting silver lining comes from Europe, as they have set now a sister association that held their first European GLUT1 meeting last fall and plan to hold it in London in 2018 and in Paris in 2020.
For me, I am looking forward to attend the 2019 meeting in Washington DC and hopefully bring on some more breaking news from my lab there.

 

 

 

[Metal] Joyeuses fete du 14 Juillet, ma liste des groupes de metal Français

Since today is the French National Holiday, I wrote down the rest of this post in my native language…..that is French! Nom de Dieu!
A l’occasion de la fete de la prise de la Bastille, qui eu lieu en ce jour, j’en profite pour mettre en avant les groupes de metal français qui peuplent ma discotheque. Si vous ne trouvez point chaussure a votre taille, il y a certainement deux raisons: soit sous êtes passe en dehors de mon collimateur, soit ne j’ai point eu un effet boeuf.
Sans trainer plus, ma liste de groupes de metal français:
Adrana (Tours, France): du metal opera avec Anne derriere la voix mezzo-soprano. Du très bon calibre.
Alkemy (Genève, Suisse): un petit groupe metal sympathique venant de nos cousins Helvetes qui font pas mal de covers, avec Katia et Jess. A découvrir.
Alwaid (Lille, France): Les chti’mis connaissent leur metal et savent l’art du raffinement. Deux albums: deux styles de metal different (le premier était dans le genre atmosphérique, le deuxième bien plus power metal) mais la meme solution détonante.
Arcadia (Mulhouse, France): Une petite pousse de l’Alsace Bossue qui avait un EP assez sympa sorti l’automne dernier.
Asylum Pyre (Paris, France): Un tres bon groupe de prog/power metal de la region IDF. Surtout de plus que Oxy Heart a récemment joint le groupe.
Au Champ des Morts (Clermont-Ferrand, France): Une découverte Bandcamp de cette année avec leur premier album intitule “Dans La Joie”. Je suis pas un fan de black metal, mais il dire que ce groupe nous fourni un sacré “sweet crude” produit raffine, surtout que c’est un des quelques bandes qui chantent en Français (ca vaut le petit coup de pouce supplémentaire). A découvrir.
Azylya (Bruxelles, Belgique): Un sacre bon groupe de gothic metal venant de nos voisins belges, avec Jamie-Lee Smit au vocal.
Blazing War Machine (Marseilles, France): Si tu cherches un groupe de metal surfant dans le black melodic a la Dimmu Borgir/power metal avec une voix feminine en premiere line, voila un groupe a découvrir. Effet cathartique assure.
Bloody Melody (Tours, France): Un petit groupe de gothic metal, alternative qui avait un son bien sympa avec leur EP. Je me demande ce que mijote dans leur marmite? Ca va faire une peu plus de deux ans et pas trop entendu de nouvelles de leur part.
Dreamslave (Lyon, France): Du power metal a la Francaise, avec memes des pépites de pirate metal. A essayer.
Ethernity (Bruxelles, Belgique): Du prog metal en provenance de Belgique, un premier album vraiment sympa.
Erzebeth/ex-Darkonelly (Dijon, France): Marion a cloture son project Darkonelly et a decide de larguer les amarres vers d’autres horizons avec son nouveau projet “Erzebeth”. Si vous êtes dans l’ambience médiévales, elle tourne actuellement avec Tony tels des troubadours quelques festivaux pour animer de sa voix suave les longues nuit d’été. En parallèle, Marion a lance son projet solo sous le nom de Marion Lamita avec deux videos en ligne: https://www.youtube.com/watch?v=OAk0Zb9lkG4 et https://www.youtube.com/watch?v=gViPbhKuajI
FT-17 (Nantes, France):  Les suédois ont Sabaton, nous on a FT-17. De plus, feru de la “Der des Ders” que je suis, aux anges de la mort fut-ce. Decouvert lors de la récente campagne Bandcamp. Du très bon calibre, avec des interludes de lettres d’un poilu décrivant les quatre années de la premiere guerre mondiale.
Heonia (Lille, France): Un autre groupe des corons. Aggressif, bimodal. A essayer!
Inhepsie (Paris, France): Un autre groupe de gothic metal chantant dans la langue de Molière.
Lethian Dreams (Paris, France): La littérature française a contribue de manière importante a la vague “romantique” du XIXe siècle, qui naturellement servi de source pour le mouvement goth et bien entendu pour le doom metal. Lethian Dreams connait son doom metal et nous en démontre sa maitrise avec trois excellent albums.
Midnight Sorrow (Strasbourg, France): Yay, un groupe de metal Strasbourgeois, symphonique de plus. De quoi être un peu chauvin, surtout que leur premier album “Pick A Tale” sorti ce printemps était un très bon robuste premier album. A essayer de toute urgence!
Pray Manticore (Toulouse, France): Un groupe de death metal de la ville rose.
Pyrah (Strasbourg, France): Un autre groupe de Strasbourg, cette fois de prog metal.
Seyminhol (Metz, France): Un groupe de power metal, si vous aimez Kamelot et chercher un equivalent Français.
Veil of Mist (Reims, France): Un groupe de metal bien sympa, a découvrir.
Whyzdom (Paris, France): La creme de la creme du symphonic metal Francais. Avec Vynce Leff derriere l’instrumentation et Marie McLeod au vocal, on a un melange detonant de baroque, d’orchestration et de rugeur de metal.