Study--Type of glucose that may help treat seizures

[Zoe]

This study showed some promising results in using a type of glucose treat seizures. I wrote to DogtorJ and asked him to comment on the science of it and how this might be done with diet.
It's a good read.



"Experimental Agent Shows Promise as Safe, Effective Antiepileptic

Medscape Medical News 2006. © 2006 Medscape

Caroline Cassels

December 7 2006 (San Diego) — An experimental agent is showing promise as an effective and safe replacement for the ketogenic diet and may pave the way for a new class of drugs to treat temporal lobe epilepsy (temporal lobe epilepsy), a new study suggests.

Presented here at the First North American Regional Epilepsy Congress and published in the November 2006 issue of Nature Neuroscience (Garriga-Canut M et al. Nat Neurosci. 2006;9:1382-1387), researchers at the University of Wisconsin, in Madison, found the glycolytic inhibitor 2-deoxy-D-glucose (2DG) has anticonvulsant and antiepileptic properties in rodent models of epilepsy.

Although still in the experimental stages, the study's principal investigator, Avtar Roopra, PhD, told Medscape the study's findings are "very exciting" and may represent a breakthrough in temporal lobe epilepsy, which is commonly drug resistant."

Link to full article:
http://www.medscape.com/viewarticle/548977_print

[RobinN]

Okay, where can we sign up. This is rather interesting/exciting news.

[Bernard]

It's a year old now. The abstract for the original article can be found here:

Temporal lobe epilepsy is a common form of drug-resistant epilepsy that sometimes responds to dietary manipulation such as the 'ketogenic diet'. Here we have investigated the effects of the glycolytic inhibitor 2-deoxy-D-glucose (2DG) in the rat kindling model of temporal lobe epilepsy. We show that 2DG potently reduces the progression of kindling and blocks seizure-induced increases in the expression of brain-derived neurotrophic factor and its receptor, TrkB. This reduced expression is mediated by the transcription factor NRSF, which recruits the NADH-binding co-repressor CtBP to generate a repressive chromatin environment around the BDNF promoter. Our results show that 2DG has anticonvulsant and antiepileptic properties, suggesting that anti-glycolytic compounds may represent a new class of drugs for treating epilepsy. The metabolic regulation of neuronal genes by CtBP will open avenues of therapy for neurological disorders and cancer.

http://www.nature.com/neuro/journal/...bs/nn1791.html

[Zoe]

I'm looking and not finding recent information about it. I sent a note to a friend who may know more and will post any new information that turns up. It does point back to what we eat. The long term effects of poor diet in relation to seizures is not much studied, we have to just figure it out on our own.

[brain]

Okay, where can we sign up. This is rather interesting/exciting news.

Robin:

You can go to:

medscape.com

or emed.com

and you can register there.
I've been registered.

Here's some other places:

nature.com <-- this is brand new & is hot hot hot
blackwell-synergy.com
lancet.com
pubmed.com
wiley.com
webmed.com

I can't think anything on the top
of my head, 'cause I'm in a hurry
right now, my good neighbor's
about to come anytime to take
me to the Pharmacy so I can pick
up my anti-epileptic drug's.

[RobinN]

Sharon I signed up for Medscape, but I was more inclined to to want to sign up for the study.

Dr. Roopra said if all goes well, clinical testing of 2DG could begin as early as next year.

those are all great sites... thank you, I will study them, when I get a chance.

[Bernard]

You can check for current clinical trials for epilepsy at clinicaltrials.gov

[brain]

Sharon I signed up for Medscape, but I was more inclined to to want to sign up for the study.


those are all great sites... thank you, I will study them, when I get a chance.

Nature.com also has an EMAIL OPTION.

I use the email option - cause it's easier
that way.



You can select all the options you want
and WHEN you want them and HOW you
want them. And through those, you get
the latest of the latest. That's how I
get the info. It also includes Research
as well.

*BOOM*

It's in my email box!

[Dutch mom]

Reading this discussion I remembered having saved this one in our files on our Dutch forum.
Still not allowed to post links, sorry , I'm doing my best to get to 50 posts.

Experimental Agent Shows Promise as Safe, Effective Antiepileptic

By Caroline Cassels
Medscape Medical News 2006.
© 2006 Medscape
December 7 2006 (San Diego)

An experimental agent is showing promise as an effective and safe replacement for the ketogenic diet and may pave the way for a new class of drugs to treat temporal lobe epilepsy (temporal lobe epilepsy), a new study suggests.

Presented here at the First North American Regional Epilepsy Congress and published in the November 2006 issue of Nature Neuroscience (Garriga-Canut M et al. Nat Neurosci. 2006;9:1382-1387), researchers at the University of Wisconsin, in Madison, found the glycolytic inhibitor 2-deoxy-D-glucose (2DG) has anticonvulsant and antiepileptic properties in rodent models of epilepsy.

Although still in the experimental stages, the study's principal investigator, Avtar Roopra, PhD, told Medscape the study's findings are "very exciting" and may represent a breakthrough in temporal lobe epilepsy, which is commonly drug resistant.

The findings emerged unexpectedly when Dr. Roopra and colleagues were investigating the regulation of genes in the nervous system. Interested in exploring the relationship between neuronal excitability, gene-expression patterns, and metabolism, the investigators used 2DG simply as means of altering metabolism to reduce the rate of glycolysis in cells and ultimately determine the effect of altered metabolism on gene expression.

Dramatic Seizure Reduction

At the same time, he said, his colleague Tom Sutula, MD, an epileptologist, was trying to determine how metabolism in general and the ketogenic diet in particular affects the nervous system in epilepsy. For almost a century it has been known that the ketogenic diet, which eliminates carbohydrates, can be effective in treating epilepsy. However, the mechanisms by which it works are still unclear.

"We realized we were both looking at the same question from different angles, and that's when we got together and began to consider whether 2DG, which is the main glycolytic inhibitor, might not only control genes but may also be of therapeutic importance in epilepsy," said Dr. Roopra.

To explore this hypothesis, the researchers subjected rats to a kindling model of epilepsy. Repeated application of electrical stimuli generates brief electrographic seizures or afterdischarges, explained Dr. Roopra. Over time, focal behavioral seizures gradually evolve into generalized tonic-clonic seizures, causing permanent alterations in the neuronal circuitry.

When the investigators added 250-mg/kg 2DG to the rats' daily diet for 2 weeks before and during kindling, they observed a dramatic increase in the number of stimuli required to induce a given severity of seizure.

No Toxicity

"The whole [epileptogenic] process seemed to reverse itself. The amount of electric current required to induce a seizure actually went up and stayed up, and that was very, very exciting," said Dr. Roopra.

The mechanism behind the antiepileptic effect of 2DG lies in its ability to reduce glycolysis in the brain. This in turn reduces the expression of genes involved in epilepsy — specifically, brain-derived neurotrophic factor and track-B receptor.

"Basically we found we could control metabolism, and in doing so we could control genes involved in epilepsy, which resulted in epilepsy itself being controlled," he said.

Perhaps even more exciting, added Dr. Roopra, was that at 6-month follow-up there was no toxicity and no weight loss or effect on cognitive performance in the 2DG animals compared with controls. "This appears to be a very safe agent with no toxicity," he said.

Palatable Alternative

Up to 50% of epilepsy patients are refractory to drug treatment, and, of these, 50% respond to the ketogenic diet. However, this mode of treatment has several drawbacks.

Adherence to the high-fat, high-protein ketogenic diet — particularly in children, where it is often used — is a major challenge. Furthermore, deviation from the ketogenic diet can result in very severe seizures. 2DG, which has the added benefit of being sweet tasting, may offer patients a much more palatable alternative if it can be administered orally.

In addition, said Dr. Roopra there are major concerns regarding the long-term impact on overall health of consuming a high-fat, high-protein diet. However, if the animal-study results bear out, he said, the simple addition of 2DG to patients' daily regimen may make it possible for them to consume a normal, healthy diet.

Dr. Roopra said if all goes well, clinical testing of 2DG could begin as early as next year.


First North American Regional Epilepsy Congress: 60th Annual Meeting of the American Epilepsy Society
Abstract 4.098.
Presented December 4, 2006.

Mom of an 8-year old boy with Lennox-Gastaut Syndrome syndrome, succesfully on the ketogenic diet

[Dutch mom]

Found more, so let's try a 'broken link', you have to glue it together yourselves and have to add www dot (I love breaking rules )


thresholdpharm.com / sec / pipe_2deoxyglucose (just delete the holes before and after the slashes.)

[brain]

Found more, so let's try a 'broken link', you have to glue it together yourselves and have to add www dot (I love breaking rules )


thresholdpharm.com / sec / pipe_2deoxyglucose (just delete the holes before and after the slashes.)

Sneaky aren't you!