Long term ceftriaxone for ALS?

Topics with information and discussion about published studies related to Lyme disease and other tick-borne diseases.
Joe Ham
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Long term ceftriaxone for ALS?

Post by Joe Ham » Sat 27 Oct 2007 2:45

What's Old is New Again - Antibiotic Protects Nerves By Removing Excess Glutamate

National Institute of Neurological Disorders and Stroke
For release: Monday, February 07, 2005

A new study shows that a common antibiotic used to treat bacterial infections increases survival rates and delays nerve damage in a mouse model for amyotrophic lateral sclerosis (ALS). The antibiotic works by activating or "turning on" the gene encoding the glutamate transporter in neurons.  This finding may lead to new drug treatments for ALS and other neurodegenerative diseases.

Jeffrey Rothstein, M.D., Ph.D., director of the Robert Packard Center for ALS Research at Johns Hopkins University in Baltimore ,Maryland , and his colleagues reported the beneficial effects of the antibiotic ceftriaxone in a mouse animal model of ALS in the January 6, 2005 , issue of Nature .* Ceftriaxone treatment, started at the onset of the disease in the mouse model, delayed the loss of neurons and muscle strength while increasing survival time.  The study was funded in part by the National Institute of Neurological Disorders and Stroke (NINDS).

The initial focus on antibiotics for ALS resulted from the NINDS-led Drug Screening Consortium, an effort in which 27 investigators, including Dr. Rothstein, screened 1040 existing drugs to assess their potential to treat a variety of neurodegenerative disorders.  Co-sponsored by The ALS Association and two Huntington's disease groups, the purpose of this cooperative drug screening approach was to use rapid technology to find new uses for existing drugs.  Ceftriaxone was one of the drugs that showed promise for ‘crossing-over' into neurodegenerative diseases.

The potentially therapeutic properties of ceftriaxone for ALS have little to do with its antibiotic effects but instead result from its ability to increase the number of glutamate transporters.  Glutamate transporters are proteins that vacuum up the excitatory neurotransmitter glutamate. Normally, glutamate acts to excite nerves so that electrical signals can travel from one to the next.

Too much glutamate has a toxic effect on nerve cells and has been implicated in neurodegenerative diseases such as ALS, Huntington's disease, Alzheimer's disease, epilepsy and stroke.

[Has excessive glutamate been shown to be present in neuroborreliosis?]

Removing glutamate through the transporter prevents nerve damage caused by excessive amounts of glutamate. "Increasing the glutamate transporter expression and removing the excess glutamate is essentially like turning on a fan to clear a smoke-filled room," says Dr. Rothstein.

As part of the Drug Screening Consortium, Dr. Rothstein found that 15 drugs from the penicillin family, named beta lactams, increased glutamate transport in cultures of spinal cord slices and therefore increased removal of this excitatory neurotransmitter.

Because this class of antibiotics can increase removal of excess glutamate, researchers hypothesized this could lead to better drug treatment therapies for neurodegenerative disorders like ALS.
"We're very excited by these drugs' abilities," says Dr. Rothstein.  "These studies show for the first time that drugs, not just genetic engineering, can increase the numbers of specific transporters in brain cells.  Because we study ALS, we tested the drugs in a mouse model of that disease, but this approach could be valuable to other conditions.  It has potential applications in numerous neurologic and psychiatric conditions that arise from abnormal control of glutamate." 

[Could this be partly responsible for Lyme Rage? Perhaps in combination with demyelination or some other mechanism(s)? ]

As a result of these recent findings, the NINDS will fund a multi-center clinical trial in ALS patients that is slated to start in spring 2005.  The placebo-controlled clinical trial will determine the safety and efficacy of long-term ceftriaxone treatment in patients with ALS. 

[This trial started enrollment July 2006. http://www.alsconsortium.org/ ]


"The discovery of new uses for antibiotics in ALS validates the drug screening approach as a rapid and effective method of finding new uses for existing drugs," says Jill Heemskerk, Ph.D., NINDS' program director for the screening program. "There are currently no effective drugs for these diseases, and the study of compounds identified by this approach will provide desperately needed inroads into this uncharted territory," added Dr. Heemskerk.

ALS and other neurodegenerative diseases are currently poorly understood, lack successful treatments and cause progressive disability in affected patients.  Dr. Rothstein and others in the field believe that having the ability to selectively target the glutamate transporter will be a powerful tool not only for treating neurodegenerative diseases but also for developing an important new class of drugs.  Since long-term antibiotic treatment could lead to antibiotic resistance or toxic side-effects, researchers are working to develop novel, less toxic drugs that are more selective in removing excess levels of glutamate. Future research will also test other beta-lactam antibiotics that may be more effective.  If successful, these drugs will shed new light on treatments for neurodegenerative disorders and help to prevent nerve damage and death in patients.

The NINDS is a component of the National Institutes of Health within the Department of Health and Human Services and is the nation's primary supporter of biomedical research on the brain and nervous system.

References: 

*Rothstein JD, Patel S, Regan MR, Haenggel C, Huang YH, Bergles DE, Jin L, Dykes Hoberg M, Vidensky S, Chung DS, Vang Toan S, Bruijn LI, Su Z-Z, Gupta P, Fisher PB.  "b-Lactam antibiotics offer neuroprotection by increasing glutamate transporter expression."  Nature ,January 6, 2005 , Vol. 433, pp.73-77.

**Miller TM, Cleveland DW.  "Treating neurodegenerative disease with antibiotics."  Science ,January 21, 2005 , Vol. 307, pp. 361-362.

By Michelle D. Jones-London, Ph.D.

Date Last Modified: Wednesday, March 09, 2005

Nick
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Re: Long term ceftriaxone for ALS?

Post by Nick » Sat 27 Oct 2007 15:25

this sounds a bit like the IDSA view on Lyme disease; if you want to know more I suggest you check this excellent website of a longtime ALS patient, Steven Shackle: http://home.goulburn.net.au/~shack/lyme.htm (also check his latest progress reports).

This site discusses a lot of ALS research, including the possible link between ALS and Lyme. The author found out at a late stage that he probably was infected with Bb and definitely improved on antibiotics (and some other treatments that help for lymies as well). A significant number of ALS victims is infected with Bb, but the medical community ignores the smoking gun and more-or-less tells patients that they have to accept that they are going to die in a few years (a bit like with MS).

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LymeEnigma
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Re: Long term ceftriaxone for ALS?

Post by LymeEnigma » Sun 28 Oct 2007 18:41

I have read that study before, and I think it really goes well with the recent study finished by Fallon et al. at the Columbia Lyme Research Center: antibiotics have a number of properties beyond their antimicrobial effects, and said properties can benefit people suffering from specific diseases and disorders beyond those that are infectious in nature. For those with chronic Lyme, this can imply a lot: the chance of chronic infection always exists, but some of us may truly be suffering no more than sequelae triggered by the infection ... but treatment options might still be available. Think about what a breakthrough it would be if Dr. Fallon and his team could isolate the part of the antibiotic that benefited these people; maybe they could eliminate a few of the side effects, as well as the threat of antibiotic resistance, while providing a viable medication with which everyone could be happy....

This is not "siding" with the IDSA. As far as I'm concerned, there are no sides; there is simply right and wrong ... and I think both the IDSA and ILADS claim a little of each. I don't think we're ever going to move forward in this controversy until we're able to rid ourselves of this black and white thinking. I believe the truth lies in one of the many shades of gray.

Or is it more important to be "right" than to find the truth?

Nick
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Re: Long term ceftriaxone for ALS?

Post by Nick » Sun 28 Oct 2007 19:31

LymeEnigma wrote: This is not "siding" with the IDSA. As far as I'm concerned, there are no sides; there is simply right and wrong ... and I think both the IDSA and ILADS claim a little of each. I don't think we're ever going to move forward in this controversy until we're able to rid ourselves of this black and white thinking. I believe the truth lies in one of the many shades of gray.
I agree that it is possible (although I have seen NO direct evidence of that yet, despide hundreds of studies from the Wormser clan that have tried to prove some kind of supposed auto-immunity problem in chronic lyme) that there are other problems besides persistent infection.

But you should acknowledge the BIG danger in these views. IDSA (and apparently this study as well) TOTALLY IGNORES the evidence for persistent infection. If they recognize that Bb causes Lyme disease, why do they ignore the persistence of the organism when talking about curing chronic Lyme? If the presence of Bb in chronic Lyme patients it not important, why bother researching Lyme at all? Why not just state that it is a fantasy disease? (probably a bit difficult as it has been proven in laboratory animals that Bb inoculation reliable induces Lyme disease ...).

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LymeEnigma
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Re: Long term ceftriaxone for ALS?

Post by LymeEnigma » Mon 29 Oct 2007 4:28

I really don't think the IDSA is ignoring the issue of chronic Lyme ... but I'd be willing to bet that they're ignoring some people, for various personal and non-personal reasons. Some of them have chips on their shoulders, but I think some of them are just as eager for the truth as we are.

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Re: Long term ceftriaxone for ALS?

Post by CaliforniaLyme » Tue 30 Oct 2007 15:51

I"ve corresponded with Halperin and was surprised to see his inclusion in the NEJM article AND that preface
in Neurology darn him because he wrote me (WISH I had kept those letters) that he was open regarding
longterm tx- that it had not been proved yet but that he was open to it being proven.

Locally we have had 4 ASlers- ONE died. Two were diagnsoed Lyme and then developed ALS years after
Lyme diagnosis, 1 diagnosed ALS one day, Lyme next (was my ex husbands business partner, had him
at Lyme doc NEXT DAY after ALS diagnosis- ONLY ALSer I know who has recovered on orals, actually just
diagnosed Babesiosis, treated with Mepron & Zith ONLY and then Doxy when relapsed later). I am SURE
it was because he was caught so early-

3 of 4 did IV Rocephin, 2 for 9-10 months, 1 died in second week of IV Rocephin, late stage bulbar onset
ALS guy who was very very weak- died of c. difficile.

THE TBE VIRUS CONNECTION (?)
3 of 4 that lived used Ledum as well as IV Rocephin.
Ledum is herb extrcat- used to be Trappers Tea used by fur trappers who got mysterious fur trapper wasting
disease. Same herbal extract discoverd by Russians to inactiviate the TBE virus. Same TBE virus that
Russians found associated with ALS. TBE viruses are flavivirae like Schu virus which was inoculated into
mice for Kochs postulates for ALS- and succeeded-hmm!!

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LymeEnigma
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Re: Long term ceftriaxone for ALS?

Post by LymeEnigma » Tue 30 Oct 2007 16:11

TBE, what is that? And Trapper Wasting Disease ... is that another name for co-infections? I know babesia made my body slowly waste away.

I think researchers will definitely find a pathogen connection to many diseases we currently take for granted as autoimmune and/or "of unknown cause."

cave76
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Re: Long term ceftriaxone for ALS?

Post by cave76 » Tue 30 Oct 2007 21:33

TBE = Tick-borne Encephalitis

Trapper's Wasting disease? --- I don't know. But I can come up with an interesting theory. :)

Wasting? Mad Cow Disease? Prions? 'TRAPPER'?

CaliforniaLyme
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Re: Long term ceftriaxone for ALS?

Post by CaliforniaLyme » Tue 30 Oct 2007 23:59

Enigma, my special interest, one of them, is ALS/Lyme. I used to web The ALS/Lyme page & need to resurrect it-

Trappers Tea!! FUR trappers!!! The gentlemen in the Old West who traded in furs, who spent days scraping skins free of ticks!!!!!! They used to (how surprising- we have a taxidermist on the meemorial page btw) come down with a sickness that fits the profile of Lyme/AlS. And Ledum was the herb they used to treat it- they found they needed to continually drink it to stay symptom free. Trappers Tea.

The RUssians studied TBE thoroughly and they found that Ledum inactivated the TBE virus.
A coincidence? I doubt it... They studied Lyme/TBE coinfection and found that many oral abx ACTIVATE the TBE virus which is what we found inthe old ALS/Lyme group- many abx speed up ALS. I have rec'ded Ledum to lcoal ALSers because one found it matetred whether he was off or on it. & I used it while on IV Rocephin when I began to have bulbar issues-

TBE virus can be sexually transmitted which fits because they have documented spousal ALS
****************************************************************************************************************

1: Zh Nevropatol Psikhiatr Im S S Korsakova. 1983;83(8):1173-9. Links

Structure of progressive forms of tick-borne encephalitis

Article in Russian
Umanekii KG, Dekonenko EP.

On the basis of long-term follow up (from 2 to 22 years) of 175 patients with various syndromes of progressive forms of tick-borne encephalitis (TBE), evaluation criteria of TBE progression are
systematized. Two basic forms of disease progression are identified: amyotrophic and hyperkinetic, each of them breaking down into a series of leading syndromes. Important for characterizing progressive forms of
tick-borne encephalitis (PFTBE) are the time when the disease began to progress and the pattern of progression as well as its stage and severity. PFTBE are correlated with the acute period syndromes.

***********************************************In long-term follow-up, 68% of patients with PFTBE display transformation of clinical forms of the disease, with the formation of the lateral amyotrophic sclerosis syndrome in the overwhelming majority of these patients.!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!(**+ ! added by me)

PMID: 6414202


1: Vopr Virusol 1991 Jan-Feb;36(1):18-21 Related Articles, Books

Experimental phytotherapy of tick-borne encephalitis.

Article in Russian

Fokina GI, Frolova TV, Roikhel' VM, Pogodina VV.

The virucidal effect of aqueous extracts of a number of plants was studied in tick-borne encephalitis (TBE) virus titration in SPEV cell culture in microplates, as well as their capacity to induce resistance in virus-infected mice. The aqueous extracts of

ledum,

motherwort, celandine, black currant, cowberry and bilberry

inactivated TBE virus practically completely,


and those of St. John's wort, pot marigold, tansy, chamomile, milfoil, and inula only partially. Studied in vivo, the extracts of motherwort, ledum, tansy and black currant induced resistance of mice to TBE virus infection assessed by the increased survival rate of the animals and significant prolongation of the average longevity. The degree of antiviral activity depended on the preparations used and the routes of their administration.


PMID: 1858353

Nick
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Re: Long term ceftriaxone for ALS?

Post by Nick » Thu 1 Nov 2007 20:47

CaliforniaLyme wrote:I"ve corresponded with Halperin and was surprised to see his inclusion in the NEJM article AND that preface
in Neurology darn him because he wrote me (WISH I had kept those letters) that he was open regarding
longterm tx- that it had not been proved yet but that he was open to it being proven.
if anything the preface in Neurology proves that he does NOT (anymore) have an open mind; his version of the story shows a totally unacceptable, unscientific, bias

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