New Lithium based therapy announced

[John1]

A new lithium (http://www.alsforums.com/definitions/lithium-als.html) based therapy for ALS was announced recently at a conference in Rome. The release is in Italian at:
http://www.diregiovani.it/gw/producer/dettaglio.aspx?id_doc=5490

I ran it through Google translator to English and then took a stab at editing the very rough output to make it more readable. I speak no Italian so my interpretation may be faulty. Results follow:

(SAY) Rome, 8 November. A new therapy can slow down the progress of ALS through the use of drugs based on lithium salts. The development team is composed of Italian scholars and researchers of Santa Lucia di Roma, Neuromed and the University of Pisa.

The news was given today during the 34th meeting of the Italian League for the Fight Against Parkinson's Disease by the same scholars, who, for 15 months, have applied the new therapy on a group of 16 patients. "In total- says Francis Bakeries, a researcher at the University of Pisa, one of the authors- the project involved 48 [ALS] patients for a period of 15 months: 16 took lithium salts with riluzole, the other 32 only riluzole" . After testing 15 months researchers have found a mortality rate of zero on patients treated with lithium salts. "The patients -explains Fornai- had been diagnosed with ALS already for a year and a high percentage had the most aggressive form of the disease,i.e. bulbar". In the other 32 patients, however, the rate of mortality "was 30%". In patients treated with lithium, then, "there was not any significant progression- continues Fornai- while in others there has been a decline of 50% in the first 3 months.
Patients were recruited from the Mediterranean neurological and neurological clinic in Pisa. The treatment is based on the following principle: the lithium could accelerate the removal mechanisms of protein and altered mitochondria and promote the genesis of new mitochondria. Another 100 patients are currently under care in a further study of the drug. Researchers will recruit others while awaiting the publication of the first results. "With this therapy is given a hope to the ill- Stefano Ruggieri, Neuromed- thanks to a drug that, among other things, costs very little."

[ZenArcher]

I've been following this since it was initially posted on the ALSTDI forums. Although I have to admit it looks extremely promising I wouldn't call it a therapy yet. A study size of only 16 patients in the test group means that chance could play a factor. Having said that since I've decided to do my own experimentation with the best test subject I know, me, I've ordered a couple bottles of lithium orotate. From what I've read the patients in this study were taking fairly high doses which I don't intend to do because I won't be under direct medical supervision for this purpose. I'm currently getting blood test done every two weeks due to elevated liver enzymes from the Rilutek and I'm hoping they'll help to catch anything amiss. Because the study size is so small and it is so early in the initial testing it's hard to cell where this will go but there have been previous theories concerning antidepressants and even some of the more skeptical researchers are showing reserved hope.

[liz]

Jeff -

It is possible to go toxic on Lithium in just a few days and it is also not uncommon. The consequences can include seizures and brain damage. If you experience dizziness, disorientation, tremors, slurred speech (worse than usual), these are signs your Lithium levels may be elevated to dangerous levels.

That said, good luck with your experiment. I'll be interested to hear if you notice a difference with your progression.

Liz

[Jamiet]

This sounds promising, Jeff, keep us informed.

do you intend to combine the lithium with the rilutek or just the lithium? If i were you, i would find a good neuro or internist to follow you, just in case.

GOOD LUCK!!!!!!!!!!!!!

If anyone here deserves to feel, get better, you are def. one of them, you are so inspirational!!

Rgds,

Jamie

[John1]

Liz, I'm glad you underscored the dangers of self-medication with lithium. In no way would I recommend anyone to try this on his/her own and the therapy is not conclusively proven yet as Jeff points out - just promising. If it does prove out, there will be no long approval period since it is already in use for other illnesses, notably schizophrenia, depressive and bi-polar disorders.

Jeff, I look forward to any results you have with your low dosage approach.

[ZenArcher]

Trust me I did my research before even thought about ordering this stuff. The levels of lithium used to treat bipolar disorder which is its normal application are much higher and are lithium carbonate not lithium orotate. I do realize there is some danger there however the dosage I'm taking is well below what is normally prescribed and is of a form that is much easier for the body to process. Lithium orotate is a supplement sold in many health food stores. I appreciate your concern and take your warning to heart.

As of right now I'm 50 mg of Rilutek so they can see what my liver enzymes do. I intend to wait until I have the results from my next blood test and then based on that I'll decide whether or not to start the lithium. I intend to inform the clinic in Hershey that I am doing this for two reasons. First so they can help keep an eye on the outcome/problems and two because I want to make sure I remain eligible for the Arimoclomol trial.

[Al]

OK guys I hate to play Devil's Advocate here but wasn't it Italy a while back that had a bunch of ALS patients sue the Gov't for access to some drug someone invented but wasn't 100% proven? and has anyone heard any good results from that? No. I'm wondering how the Italians come up with these startling new breakthroughs but only with small groups and no one else does. Makes me wonder. But I'm a skeptic by nature.
AL.

[liz]

Fair question, for sure. But at least in this case the treatment is relatively low cost and, with good monitoring, relatively low risk. When Jeff announces he's jetting off to Costa Rica for the latest in stem cell therapy, then I'll start to worry. But I'd be happy to go along for the ride :).

[ZenArcher]

No worries I have no intentions are getting any stem cell therapy at any point in the near future. Supplements I'm willing to try. The Italians recently sued the government for access to IGF and won. There are several people currently undergoing treatment with IPlex and hopefully the outcome is good and that will lead a future clinical trials but that remains to be seen. The Italians aren't the only ones that have been interested in lithium. There've been several articles written on the effects lithium has on the nervous system and even some with respect to ALS.

Shin JH, Cho SI, Lim HR, Lee JK, Lee YA, Noh JS, Joo IS, Kim KW, Gwag BJ.
Department of Pharmacology, Ajou University School of Medicine, Sawon, Korea 442-749.
The Fas pathway and oxidative stress mediate neuronal death in stroke and may contribute to neurodegenerative disease. We tested the hypothesis that these two factors synergistically produce spinal motor neuron degeneration in amyotrophic lateral sclerosis (ALS). Levels of reactive oxygen species were increased in motor neurons from ALS mice compared with wild-type mice at age 10 weeks, before symptom onset. The proapoptotic proteins Fas, Fas-associated death domain, caspase 8, and caspase 3 were also elevated. Oral administration of 2-hydroxy-5-(2,3,5,6-tetrafluoro-4-trifluoromethyl-benzylamino)-benzoic acid (Neu2000), a potent antioxidant, blocked the increase in reactive oxygen species but only slightly reduced activation of proapoptotic proteins. Administration of lithium carbonate (Li(+)), a mood stabilizer that prevents apoptosis, blocked the apoptosis machinery without preventing oxidative stress. Neu2000 or Li(+) alone significantly enhanced survival time and motor function and together had an additive effect. These findings provide evidence that jointly targeting oxidative stress and Fas-mediated apoptosis can prevent neuronal loss and motor dysfunction in ALS.

Pasted from <http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17105868&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubme d_ResultsPanel.Pubmed_RVDocSum>


I do my own research and draw my own conclusions. I understand and appreciate the caution and skepticism and I have it as well but I'm willing to spend the $12.00 and give it a try. Modern medicine has had 138 years to find a treatment and to date we of Rilutek. Do I believe this will work, maybe. Do I recommend that anyone else give this a try, of course not. As the old saying goes, "what doesn't kill me makes me stronger" and I'm not dead yet:)

[Al]

As I said I am a skeptic but just started taking a supplement that was provided to me free by the manufacturer/distributor after contacting me after seeing the Globe article. They were telling me how great their product was so I said put up or shut up more or less. So I have a 6 months trial supply. I'm not going to say what it is for a while to see if it has any benefit first. I am willing to try something that isn't going to break the bank too on the off chance it might help. Some of these supplements do work. Others are scams. Sorting out which is which is the fun part.
AL.

[Bluenadski]

I've been following this since it was initially posted on the ALSTDI forums. Although I have to admit it looks extremely promising I wouldn't call it a therapy yet. A study size of only 16 patients in the test group means that chance could play a factor. Having said that since I've decided to do my own experimentation with the best test subject I know, me, I've ordered a couple bottles of lithium orotate. From what I've read the patients in this study were taking fairly high doses which I don't intend to do because I won't be under direct medical supervision for this purpose. I'm currently getting blood test done every two weeks due to elevated liver enzymes from the Rilutek and I'm hoping they'll help to catch anything amiss. Because the study size is so small and it is so early in the initial testing it's hard to cell where this will go but there have been previous theories concerning antidepressants and even some of the more skeptical researchers are showing reserved hope.

Jeff, what dosage are you taking?
I was wondering - my mother has PBP and I've been looking at this closely. Her neuro says research has been promising but nothing groundbreaking or solid yet. Therefore, roughly translated - this therapy will not be available for at least 4-5 years under UK HC system.
Let me know. I'vebeen seeing general doses per tab at 120mg PU. Not sure if this is safe or way too much.... any info you can give will be welcomed.

Thanks,
Nada :-D

[ZenArcher]

That's about where I'm starting when/if I start. The information I got on the trial was a much higher dosage but it was also the prescription lithium carbonate. Just remember this is not something to jump into lightly. Do your research and talk with a health care professional. Even supplements can interact with one another or prescriptions. Caution and skepticism are very good traits to have under these circumstances.

[liz]

So what are you saying, Jeff? The trip to Costa Rica is off? I'm very disappointed. :|

[ZenArcher]

Australia or bust :)

[Bluenadski]

That's about where I'm starting when/if I start. The information I got on the trial was a much higher dosage but it was also the prescription lithium carbonate. Just remember this is not something to jump into lightly. Do your research and talk with a health care professional. Even supplements can interact with one another or prescriptions. Caution and skepticism are very good traits to have under these circumstances.

Thanks Luv!

What I wanted to hear...

I have been looking at this closely for the last couple of years - strangely before my mother was diagnosed. I've always had a strange interest in neurological illnesses.
My brother has Autism in mild form with borderline schizophrenia - with my mother displaying similar traits (somewhat diluted to depths of aspergers). For the depression which accompanies autism/aspergers I started looking at lithium and the effect it had on symptoms. Following on I discovered the fascination European medicine held with Lithium and treatment for such ailments.

I, as ridiculous as it may sound - feel instinctively positive about these trials. My instincts (without blowing my own trumpet) generally tend to be spot on.
Call me mad - but from what I have read on active studies etc am genuinely excited about this area of research.

My mothers neuro was not negative when I mentioned the possibility of starting lithium. He is incidentally the chairman of the MND (ALS for US) association of Scotland. To me - thats enough. :-D

[jimercat]

Good luck Jeff!

We gave this info last week to Emory ALS research nurse, who said she had not heard of anything like this.

The resident pooh-poohed Lithium saying there were horrendous side effects. HA! HA! HA! I think PALS may be willing to put with some side effects!

Please keep us informed brave soul!

[koopie33]

So, are they doing the lithium salts in the U.S.? You'd think they'd be trying absolutely everything to get this disease stopped.

[Steve100]

Any news on this? Any luck with your new treatments Jeff or AL?

Thanks

Steve

[ZenArcher]

I've been taking Lithium Orotate along with my Rilutek at 50 mg/day for a little over two weeks now. I haven't had any side effects, my blood work AST/ALT came back normal. After only two weeks I didn't really expect to see results yet. The only things I can report are after a week I had some muscle soreness in my gluts which lasted for about two days. The soreness is the kind you get after you did too much and the muscle gets sore. A few days later I had the same thing in my left shin. This could be complete coincidence and for right now I take it as that but those were the last two places I experienced weakness. If I go back to clinic in three months and have shown improvement in strength then I'll be a little more excited until then I'm assuming any perceived improvement is placebo effect.

[Steve100]

Hi - I Didn't check the date on your posts.....I can't believe its only been two weeks. My perception of time is way off, I don't even know what day it is half the time :D

Good luck

Steve

[kdnycity]

Found this on another ALS forum.

Nov 23, 2007

Lithium "to slow down, with a certainty in excess of 95%, the progression of ALS". These exceptional results came out from an Italian study on 48 ALS patients, 32 treated with standard therapy of riluzol, 16 treated with riluzol and lithium. These results have already been submitted to a well-known international journal that is now verifying the data and may publish the report shortly. "15 months after the start of the study, 30% of the patients treated only with riluzol died. In the second group there were no deaths, even though half of the patients in the group had the most aggressive form of ALS, that is bulbar". This is what one of the Italian researchers, experimenting with the use of lithium against ALS, Francesco Fornai, associate professor of the department of Human Morphology and applied biology at the University of Pisa, stated. Furthermore, utilizing parameters from the neurological scale to measure progression, there was no significant deterioration of the ALSFRS-R, while the decline was evident within 3 months in the other group. At the end of the study the decline was measured at 50%. A preview of this study was given on Nov 8, 2007 during the XXXIV LIMPE Congress, the Italian league in the fight against Parkinson's disease.
The neurodegenerative pathology and ALS, explain the researchers, have many common elements. Funds permitting, lithium will also be studied against Parkinson's disease. In the meantime, the Italian study may obscure patient's expectation of the other study due in January 2008, that is the US study on the Igf-1.
The attention on therapies against ALS has intensified in Italy since the Ministry of Health decided against the treatment of patients with the drug Igf-1 or the combination Igf-1/Igf-Bp3.
Fornai started to study medications not provided by the Healthcare system in Italy, which patients have had to go through the Courts to obtain. Fornai started to study the effect of lithium 2 years ago on mice genetically modified to develop ALS, starting with the capacity of this substance to intervene on certain cellular degenerative processes. "As I proceeded with the research I noticed how lithium would slow down other cellular damaging mechanisms."
The Italian researcher explains how, with appropriate distinctions, ALS and Parkinson are similar in the effect they have on cells. " In the first a slight compromise of the damaged neurons in Parkinson, in the latter we noticed spinal damage as in ALS". Lithium, known as a treatment for bipolar conditions, "accelerates mechanism to remove proteins and altered mitochondrion. It also increases the speed that cells dispose of signs of the decease, practically freeing themselves.
Lithium always promotes the birth of new mitochondrion. Therefore, it does not block the gene that triggers the decease but it accelerates at that point the replacement to stop the progression, a process that the third characteristic of lithium contributes to, i.e. neurogenesi. In some stem cell studies, it was observed how this substance increases the survival in the bone marrow."
Since the first tests were concluded, one hundred more patients are now under treatment, under a new protocol established with the Italian Drugs agency (AIFA). "If the positive results are confirmed by this new study, the sampling will be even larger. Likely, colleagues in the rest of the world will do the same".
The Italian scientist will continue his research in this area but adds: "we have to try other molecules such as Rapamycin (sirolimus) that in contrast to lithium is more expansive" Although the road is clearer, the hunt is not over. It is a project that the University of Pisa is undertaking with IRCCS Neuromed, the west Piedmont University, the IRCCS Santa Lucia and the teaching polyclinic Sant'Andrea in Rome.

The link to the Italian publication is as follows:
http://staminali.aduc.it/php_newsshow_0_6473.html

This article was published in a publication called
Stem Cells
bi-weekly publication
Cellule Staminali ( http://staminali.aduc.it)
bi-weekly news on therapeudic cloning
Edited by: ADUC ( association for the rights of users and consumers)
Via Cavour, 68 -50129 Florence Italy
Tel 055-290606 Fax 055-2302452
aduc@aduc.it

Year 2007 Number 153 of Nov 23,2007

Best,
Kathy

[mikebharrington]

Good news! The Italian study has been accepted for publication in the Proceedings of the National Academy of Sciences. This is an important step that really speaks to the quality of the study.

Best,

Mike

[ses76]

I was looking at this link the other day and was interested in the information. The link is not working now....any info on this???
Thank you

[Al]

Just worked for me.
AL.

[ses76]

Works for me now too.... must've been down for some reason. Thank you!

[vmd]

If I'm reading the information correctly on the link provided above, those who are taking part in the informal study of lithium are doing well. That is, their scores have either improved or remained stable. I do see one problem, however. the ALSFRS-R score can only go up to 40, which identifies no problem, yet some of the participants have scores higher than 40?

[ZenArcher]

The ALSFRS-R has a high score of 48. 12 questions scored from 0 to 4.

[vmd]

Zen:

I took the scale on the link provided and selected normal for all questions just to see the highest score and it was 40. What am I missing?

[ZenArcher]

I haven't checked the one at that page. PatientsLikeMe uses the ALSFRS-R in its calculations and the high is 48. I think the original ALSFRS had a high of 40 but I'm not sure. Sorry didn't read the whole thing the first time.

[vmd]

Jeff:

Yes, I see. I probably took the older version, then. Do you have a link to the newer version?

[ZenArcher]

https://psg-mac43.ucsf.edu/als/ALSFRS.asp

[ilgal]

Yesterday I went to my GP's PA who is my primary care provider. I took all the info I could find on the lithium and she agreed to prescribe and monitor via blood tests. She wrote script for lithium carbonate 150 mg twice a day. I'm getting from my insurance company's mail order pharmacy and a 90-day supply will only be $11. It will be about a week before it arrives and I begin taking it.
I'm definitely not a person who would fly off to a foreign country and spend beaucoup bucks on an unproven therapy. But low cost and a physician who will monitor (bless her!)--why not?!!
Keep your fingers crossed!

[vmd]

Jeff:

Thanks for the link.

Ilgal:

Let's pray that it helps. By the way, most of the research that I have seen is with lithium combined with riluzole. Are you taking both or just the lithium? I also read that it needs to be lithium carbonate, not lithium orotate, as dosage levels have been established only for the carbonate form.

[ilgal]

I am not taking riluzole. I opted not to at the beginning because the benefits are so negligible. I can't find anything that would indicate it is the combination that is effective, but I do plan to ask neurologist when I go in April.

[vmd]

I am not certain whether it is the combination that is effective either. I'm sure that future trials will compare different treatment groups, including a lithium only condition.

[bala80]

Hi Jeff,

I was wondering why you opted for the lithium orotate rather than the carbonate as used in the study.... also are you being monitored for blood lithium levels to be 0.4 mg/L as mentioned in the study?

I know it is natural to be skeptical about this, but if I'm not mistaken it was mentioned that "there was no progression in the lithium group, whereas there was a 50% decline in 3 months in the riluzole group". That is a pretty massive statement, and my first reaction was to be skeptical as well. But since hearing the study has been accepted into PNAS my hope has risen enormously. I say that because I have been a biochemistry researcher into Type 2 Diabetes and known how prestigious this journal is, and how precise and important a study must be before it is accepted.

And as for side effects, bring on any side effect under the sun, as long as it stops progression I don't care.

[ZenArcher]

I started on lithium orotate simply because I didn't have enough information at the time to think that I would be able to get a prescription for lithium carbonate. Also the element of concern is lithium which exists in both the orotate and carbonate forms. You can do a search on PubMed and find several studies on orotate. I am awaiting a standing order from my GP now that the blood levels have a little more fact behind them and will update once I get the results.

[ilgal]

My lithium carbonate arrived in yesterday's mail so I took my first dose this a.m. I will continue twice a day and have blood test Mon. a.m. My fingers and toes are crossed!

[vmd]

I'm pulling for you ilgal. How are you going to keep track of the change in symptoms? Use the ALSFRS scale?

[janetraden]

Dear Nada,

In a message a while back you said: "My mothers neuro was not negative when I mentioned the possibility of starting lithium. He is incidentally the chairman of the MND (ALS for US) association of Scotland. To me - thats enough".
May I ask yo uif he since has prescribed lithium? I'm asking because my husband's neurologist was aaginst prescribing lithium, however when I mentioned what I remembered from your message he bacame interested. So I'm thinking, if your mother's neurologist did end up prescribing it, and if you could possibly passs me his name, this might help persuade our neurologist. Do you think you could help?
Thank you!
Maren

[ilgal]

vmd,
Yes I'm going to use the ALSFRS scale. There is an informal "study" tracking scores of people taking lithium at the ALS-TDI website, so I'm going to periodically send them my scores and have it added to their database. The dau of a PALS is doing it and she is a PhD research scientist so she will be doing some statistical analyses of the numbers. I think the important thing for those taking lithium is to get to and keep the correct blood level. I have my first blood test Mon. morning and hope I'm reaching the possibly effective level quickly.

[vmd]

Yes, the blood levels are critical in making certain you are in the right level with gaining the therapeutic effect and yet keep the toxic effects under control.

[dbw]

I have some concern about the creditability of the Italian Lithium trial. First, it was not list on the NIH's ALS clinical trails site (http://clinicaltrials.gov/ct2/results?term=Amyotrophic+Lateral+Scleros is), where some Japanese, French and other foreign countries' clinical trials have been listed there. Second, how come the control group has 32 patients while lithium group has only 16 patients? Third, I wonder if the patient in the control group has ever been given the placebo.

[AHands]

a california newspaper reporter dx'ed with als ran a story on Li today: http://www.sbsun.com/news/ci_8088813

are there decent food sources of Li? most of the stuff i've read just gives the broad "vegetables and grains". some mention lemons, but others say "no" and that citrus plants do poorly in Li-rich soils. Tap water in some parts of the world is high in Li. Perhaps "which vegetables" varies widely depending on groundwater Li where they were grown?

[Mark]

Hi,


I doubt that you will an adequate fóod source for lithium. I have prescribed it for years for patients with mood disorders. It never seen anything in the literature about deriving this from food. It doesn't mean it isn't possible. If you do find any information that would be interested in seeing it. The Italian lithium study how to be published in the next few weeks in what I understand is a credible. Góod luck.

Mark

[Mark]

I just reread my post from yesterday. The errors are due to my voice recognition program which has difficulty on this and other web sites. At any rate if you find information about lithium from food sources please let me know. Also, as I was trying to say, the Italian study on lithium ought to be published within the next few weeks and it is my understanding that he is in a reputable journal.

Mark

[vmd]

dbw:

Experimental and control groups do not have to have the same exact numbers of subjects. However, it is a good idea. I would be more comfortable if I knew that there was random assignment to the experimental and control groups in the study. If those that were chosen for the lithium group were systematically selected to be in the experimental group, that would certainly compromise the results of the study. Apparently, as Mark says, the Italian study will be published in a very reputable journal here soon. Let's pray for the best.

[sharonca]

I plan on seeing my GP to get started on Lithium on Thursday. I'm taking him all the info I can find on the study and he will monitor my blood levels, etc. Anyone know what Lithium costs? I have not paid up my deductible yet this year. I do take Riluzole and will continue with that. I've been pulling everything I can find on the subject. Wish me luck!

Sharonca

[bala80]

Lithium carbonate in the States is very cheap for 150mg pills:

http://www.drugstore.com/pharmacy/prices/drugprice.asp?ndc=00054252625&trx=1Z5006

Good luck getting a script for it. I've read on the ALS-TDI forum some PALS have been having problems getting a script from their neuros. Bloody outrageous if you ask me.

[AHands]

Food sources

Lithium in vegetables depends on
1. the species,
2. the soil they grew in and
3. the time of year harvested.

Species

Citrus plants do poorly in Li soil. Alfalfa accumulates almost no Li.
Tobacco concentrates a lot of Li.
High Lithium has been reported in cabbage, kale, chard, spinich, onion and raddish.

Soil

Lithium is highest in acidic igneous alumino-silicate sedimentary rocks
earths crust: 20ppm
Clay & shale deposits: 100ppm
Limestone & sandstone: low
Clayton valley Nevada: 1600ppm - 10000ppm (enclosed basin). Similar areas are reported in California and Arizona.
Largest accumulations: salt lakes on the Tibetan plateau
Andes, Rift Valley, Red Sea, Persian Gulf, Ethiopia, Turkey
elevated levels of groundwater Li are found in the southwestern united states, Florida and S Dakota

Harvest

Li content in plants is highest in the dry season



A study from India found high levels in: coriander leaves, tamarind, tomato and garlic.

Spices such as nutmeg, cummin seeds and coriander seeds had high lithium content. The lithium content was high in various cereals and pulses like pearl-millet, black-gram, and chawli seeds; while rice and wheat contained very little lithium.
Lithium content was also found to be high in rock salt and commonly used crude sea salt as compared to refined table salt.
The highest amount of lithium (12 µg/gm) was detected in tobacco.

They also found a nonvegetarian diet to contain nearly twice as much Li as a vegetarian diet.

[AHands]

I got an Rx for Lithium and will start in a few days, after switching to a Lithium-compatible blood pressure med.

[mikebharrington]

Here's a link to the study on the PNAS website:

http://www.pnas.org/cgi/reprint/0708022105v1

Finally, no more speculation about the study results! Not a cure, but the results look very promising.

[joe stockton]

First, reading the Italian trial report and then reading through the posts. I'd like to ask a few questions. From my understanding there is no accurate blood test or way to determine a person has ALS other than sometimes exhaustive testing. 1) How would these Italian Scientists determine that the progression of ALS has slowed in the 16 patients? Would this be through comparative observation or other methods?

Secondly, due to the drastic natural of ALS. Will this force ALS patients on to the blackmarket or foreign countries (in US) to aquire lithium or do you think doctors will allow patients to us the combo, under supervision? thoughts. Joe

[AHands]

1) How would these Italian Scientists determine that the progression of ALS has slowed in the 16 patients? Would this be through comparative observation or other methods?


It's my understanding that in both the mice and human study, there were clearly observable deaths in the control group. In the mice, they observed spinal cells under the microscope and found that lithium increased the number of healthy mitochondria in the both the ALS and healthy mice. In the human study, efficacy was demonstrated in:
observations (ALSFRS-R, Norris scale, MRC scale), and
measured breathing capacity (FVC),
in addition to survival (30% of the control group was dead at the end of the fifteen months).

Secondly, due to the drastic natural of ALS. Will this force ALS patients on to the blackmarket or foreign countries (in US) to aquire lithium or do you think doctors will allow patients to us the combo, under supervision? thoughts. Joe

I went to my family doctor and got a prescription.

[Al]

Quite a few on the forum here have started the treatment so it can't be too hard to get a script.
AL.

[joe stockton]

Can someone please explain how these researchers arrived at a reluzole/lithium combo This just cant be random? Is it routine to pair a wide array of drugs with an approved ASL drug? So where they testing various combinations with reluzole in the mice study and just hit on one (lithium)?

This really is an exciting event. It reminds me when the first AIDS cocktails came out and showed promise...look where that research is today. Let keep our fingers crossed! And a little prayer too.

[ZenArcher]

The Rilutek, lithium combination was tested because researchers can not make some stop taking Rilutek because it is the only approved drug for the treatment of ALS. Because of that almost every test you see includes Rilutek (creatine, minocycline, arimoclomol, etc). Lithium was tested because it has show many neuroprotective properties in the past as well as affecting other suspected mechanisms of ALS.

Arimoclomol a co-inducer of HSP-70. http://www.ncbi.nlm.nih.gov/pubmed/17656567
Lithium an inducer of HSP-70. http://www.ncbi.nlm.nih.gov/pubmed/16797496 and http://www.ncbi.nlm.nih.gov/pubmed/12732732

Minocycline appears to inhibit GABA production. http://www.ncbi.nlm.nih.gov/pubmed/3382463 also there was a study done showing that permethrin based pesticides at high enough exposures could cause a motor neuron disorder which mimics ALS http://www.ncbi.nlm.nih.gov/pubmed/17130437. Permethrin based pesticides work by inhibiting GABAA receptors http://www.safe2use.com/poisons-pesticides/pesticides/permethrin/cox-report/cox.htm.
Lithium increases plasma and CSF GABA. http://www.ncbi.nlm.nih.gov/pubmed/6403063

Lithium inhibits glutamate uptake. http://www.ncbi.nlm.nih.gov/pubmed/9653192

Last but not least is oxidative stress http://www.ncbi.nlm.nih.gov/pubmed/17548157

None of this proves anything, it was just some of the research that I did before talking to my neuro about taking lithium.

[Al]

Thanks for the fill in Jeff.
AL.

[JustMe]

Specifically to ZenArcher - -

- as you are local, have you or anyone you know of locally been able to get our local ALS people to put you/them on Lithium? I have no tried our friends at Hershey - I'm pretty sure I know what thqat answer would be. I have approached my GP - PPCP about it, but no answer from him as yet after two weeks.

THis is rather rediculous - help is just NOT available here in PA. YOYO - You're On Your Own.

ROY

[ZenArcher]

Roy,

I went to clinic last Wednesday and walked out with a script for Lithium without having to argue at all. Dr Simmons and I had a short discussion and that was it. I was the first that much I know.

[kmgy]

I really like Dr. Simmons. You are under great care. Did Dr. Simmons say he was going to continue to prescribe lithium? I went with my father to all his appointments with Dr. Simmons. Susan is wonderful too.:mrgreen:

[ZenArcher]

In all honesty I didn't ask. I had sent him the report as soon as it was published and he had talked with another neuro about it prior to my visit. I know that in discussing other possible treatments such as low dose naltrexone he had always been willing to go off label if it made sense.

I was with Susan, Shelley and Judy as well as a good portion of the Philly crew in Harrisburg yesterday for PA ALS Awareness day at the capitol building. I was one of four PALS there. We had a good time and I believe helped personalize the disease and the legislature for quite a few of our state reps. I would highly recommend it to all that are able.

[vmd]

Jeff:

Thanks for posting a pic of yourself, and, who, I presume is, your better half.

[Al]

Naw. That must be his daughter.
AL.

[ZenArcher]

Yup, that's the ole ball & chain (Tam) just don't tell her I said that.

As for Al, she's mine back off :-D

[Al]

Cute. Her, not your comment. Much too young looking for an old fart like you. By the way 6 went and got scripts today. No problem.
AL.

[ZenArcher]

Just for that old fart comment:

Old is when... (http://www.alsforums.com/forum/showthread.php?p=37551#post37551)

[joe stockton]

seems several prominent italian soccer players have come down with ALS, so over the last few years its been getting media attention over there...maybe this prompted a greater demand on italian researchers...dont know...but the lays out more detail as to how they arrived where they are today. good read and very promising.


http://www.ansa.it/site/notizie/awnplus/english/news/2008-02-07_107179176.html

[joe stockton]

http://cbs4.com/topstories/ALS.Lou.Gehrig.2.395410.html

the above story relates to italian soccer star in significant numbers coming down with ALS. I remember what impact Magic Johnson had on AIDS research when he announce he had the virus. It was a national headline here. Needless to say, these Italian Soccer plays are pretty prominent, many are stars. Do you suppose this had an impact on developing this agressive research in Italy?

[Jeliota]

I'm kind of inwardly groaning to post this here, as what I have CFS is really nothing in the whole big scheme of things, but I thought that some of you might find it interesting that I started taking lithium orotate (bigger molecule, less lithium than carbonate--if you have ALS, don't self-treat with orotate) a couple of months ago and my symptoms are very, very nearly non-existent right now. I'm only taking 20 mg of elemental lithium per day, and it's the only thing (other than the craziest placebo effect I've ever heard of) that I can think of that would have stopped this thing. I had non-stop, bodywide twitching and endless muscle pain. Now, nothing.

In addition, looks like they are already looking at lithium in a number of other neurodegenerative conditions. I'm betting this stuff is for real, no matter how small this first study was.

[ZenArcher]

Given the limited amount I know about CFS I don't have a problem believing it would have an impact. Lithium has been researched as a neuroprotective for years. PubMed has articles referring to lithium as a neuroprotective dating back to 1991 so seeing it go to trial for other neurological conditions makes sense. Since the Italian study has been published I'm willing to bet you'll see trials for several others surface in short order.

I am cautiously optimistic as I said to Jamie in a PM earlier today. Lithium has impacts on several of the proposed mechanisms of ALS which I posted earlier in this thread.

[kelly]

Jeff,
Thanks for all your great research and investigative work. Your postings encouraged me to request lithium for my husband. From what you have posted, you sound like you are at the same stage phsyically. Who knows.....lets hope for our miracle. Kelly

[ZenArcher]

Kelly, I'm hoping for the best. I see you're from Saratoga Springs. I lived in Ballston Spa right on route 50 for 4 years. There was a little diner, I can't remember the name, on the left hand side if you are going south of 50 and my driveway came off their parking lot. It was two blocks before the McDonalds. Of course this was more than 10 years ago now.

If you saw me walking down the street you wouldn't know. In fact I was at PA ALS Awareness day in Harrisburg on Monday and several of the ALSA people that work at a different clinic didn't know I was a patient until I told them. I'm not complaining in the least :) My left hand is weak but workable. My biceps are weakening as are my shoulders. Other than that I'm starting to get some fatigue in my shins which leads to "foot slap". All in all considering my first symptoms were 2 1/2 years ago I'm not going to complain one bit :-D

[Jeliota]

Given the limited amount I know about CFS I don't have a problem believing it would have an impact. Lithium has been researched as a neuroprotective for years. PubMed has articles referring to lithium as a neuroprotective dating back to 1991 so seeing it go to trial for other neurological conditions makes sense. Since the Italian study has been published I'm willing to bet you'll see trials for several others surface in short order.

I am cautiously optimistic as I said to Jamie in a PM earlier today. Lithium has impacts on several of the proposed mechanisms of ALS which I posted earlier in this thread.


Hey, thanks for that great link. I'm going to go and look at that in depth here in a minute, but it looks very well done at quick glance.

The thing about CFS is that we don't know what causes it. Some claim it's in the muscles, others claim there is something irritating the nerves, others claim it is a potassium ion channel problem. Given that we don't know the exact mechanisms of Lithium, either, (though it does appear to be protective against glutamate excitability and has some other documented functions) I figured that, hey, my nervous system is not acting normally for unknown reasons, and since all of lithium's mechanisms are not fully understood--heck it makes the grey matter in very particular parts of the brain grow--I would give it a try. I had little to lose at the levels I was taking. My symptoms were fatigue, cramps, constant bodywide twitching and weakness--all common for CFS. Yet my EMG/NCV and nuerological exams were normal. I didn't even have a hint of any fibs, for instance. So I tried it ,and it worked for me. Now, I haven't recommended it to any other CFS'ers. If this were aboutcfs.com, I wouldn't have mentioned it at all. One person is not a trial. Plus, CFS can spontaneously go into remission, though that's pretty rare.

Anyway, you are probably right, but my symptoms were severe and now they are gone. If it were something like sleeplessness, I could go with the placebo effect. Actually, that would be fine--whatever works. But, as I said, I had very severe CFS symptoms and now I have nothing. I have to think that something specifically stopped it, and the only changed I made was lithium.

Anyway, wherever the truth lies, I'll not quit it, that's for sure.

Again, thanks for the site. Can't wait to go through it.

[Jeliota]

Ah, Zen Archer, apparently the lithium isn't helping my reading skills. You said you DIDN'T doubt it, so I guess you weren't intersted in my thought processes, huh?:-D

Oh, well, I always look for chances to engage in uncontested soliloquies.

Just finished looking at that site. Just fantastic work.