Editing Proleariat Protocol - added text after copying the original. To be edited before translation.
Warning: You are not logged in. Your IP address will be publicly visible if you make any edits. If you log in or create an account, your edits will be attributed to your username, along with other benefits.
The edit can be undone.
Please check the comparison below to verify that this is what you want to do, and then save the changes below to finish undoing the edit.
Latest revision | Your text | ||
Line 1: | Line 1: | ||
− | |||
− | |||
− | |||
== The Pile of Pills == | == The Pile of Pills == | ||
Line 19: | Line 16: | ||
<li> '''Vitamin E complex''' (natural mixed tocopherols and tocotrienols). These can be purchased separately, but my personal preference is "TOCO-SORB", Jarrow #112026, which has everything in one softgel that's small enough to actually swallow. LEF has recently introduced Gamma E Tocopherol/Tocotreinols #00559 which as far as I can tell is the same thing. </li> | <li> '''Vitamin E complex''' (natural mixed tocopherols and tocotrienols). These can be purchased separately, but my personal preference is "TOCO-SORB", Jarrow #112026, which has everything in one softgel that's small enough to actually swallow. LEF has recently introduced Gamma E Tocopherol/Tocotreinols #00559 which as far as I can tell is the same thing. </li> | ||
<li> '''B-complex.''' Most so-called "B-50" formulations (for one a day dosing) seem fairly good, but read the label details before buying. B6 (pyridoxine) is important, but don't supplement more than 50 mg/day: http://www.als.net/forum/yaf_postst53654_Vitamin-B6.aspx Be warned also that quite a few nutritional supplements you wouldn't expect B-6 in contain B-6: read the fine print on the label. ...There's a whole slew of B-vitamins with different possible impacts on ALS, and it's going to take years to figure out what sort of combination is optimum. Some people are really big on B-12: if you're going to bother, go all the way to 5 mg/day methylcobalamin separately from your B-complex. ....12 April 2014 I started a new thread on B-vitamins: http://www.als.net/forum/yaf_postsm384696_B-vitamin-supplementation-in-ALS.aspx#384696 | <li> '''B-complex.''' Most so-called "B-50" formulations (for one a day dosing) seem fairly good, but read the label details before buying. B6 (pyridoxine) is important, but don't supplement more than 50 mg/day: http://www.als.net/forum/yaf_postst53654_Vitamin-B6.aspx Be warned also that quite a few nutritional supplements you wouldn't expect B-6 in contain B-6: read the fine print on the label. ...There's a whole slew of B-vitamins with different possible impacts on ALS, and it's going to take years to figure out what sort of combination is optimum. Some people are really big on B-12: if you're going to bother, go all the way to 5 mg/day methylcobalamin separately from your B-complex. ....12 April 2014 I started a new thread on B-vitamins: http://www.als.net/forum/yaf_postsm384696_B-vitamin-supplementation-in-ALS.aspx#384696 | ||
− | + | ||
− | + | B-1 (Thiamine) deserves special attention (see http://www.als.net/forum/yaf_postst44708_Foot-drop-and-thiamine.aspx ). Here's a summary I posted about page 5 in that thread: | |
Most of the posting relating to thiamine is over my head, but I do skim through it anyhow hoping to absorb some information by osmosis. The encouraging PubMed is tempered by an anecdotal report of benfotiamine toxicity. | Most of the posting relating to thiamine is over my head, but I do skim through it anyhow hoping to absorb some information by osmosis. The encouraging PubMed is tempered by an anecdotal report of benfotiamine toxicity. | ||
− | + | ||
Here's my tentative summary of what I think I've seen so far. | Here's my tentative summary of what I think I've seen so far. | ||
− | + | 1. Thiamine deficiency is very common in ALS, probably because of genetic abnormalities and/or disease processes rather than inadequate dietary intake with food. | |
− | + | ||
− | + | 2. Therefore supplementation is advisable at a level many times the RDA (1.6 mg). So-called "B-50" formulations usually contain 50 milligrams, or nearly 35 times the RDA. | |
− | + | ||
− | + | 3. Because benfotiamine is lipophilic (and perhaps for other reasons also), it has pharmacological actions of types believed to be beneficial in ALS, which go beyond what you get from regular thiamine. Therefore benfotiamine is the preferred form of thiamine supplementation. | |
− | </li></ol> | + | |
− | + | 4. Ordinary B-complex vitamin "pills" always include thiamine but to my knowledge never include benfotiamine. Therefore benfotiamime supplementation has to be done separately. | |
− | http://www.als.net/forum/yaf_postst49608_dl3nbutylphthalide-Another-Drug-With-Exciting-Preclinical-Result.aspx#353299 | + | |
− | + | </li></ol> | |
+ | |||
+ | 14. Trimethylglycine (TMG, Betaine). The addition of TMG to the list emphasizes lower motor neurons: see Persevering's "Fasciculations" thread for more details. http://en.wikipedia.org/wiki/Trimethylglycine TMG is also a methyl donor which (like methylcobalamin B-12 and methylfolate helps to suppress the inflammatory factor homocysteine. | ||
+ | |||
+ | 15. 3nB (celery seed extract) anti-inflammatory, gliosis inhibitor | ||
+ | http://www.als.net/forum/yaf_postst49608_dl3nbutylphthalide-Another-Drug-With-Exciting-Preclinical-Result.aspx#353299 | ||
+ | |||
+ | 16. ibuprofen anti-inflammatory, anti-gliosis, disinhibits neuron repair. http://www.als.net/forum/yaf_postst53530_pain-med-suggestions.aspx | ||
http://www.ncbi.nlm.nih.gov/pubmed/17428993 | http://www.ncbi.nlm.nih.gov/pubmed/17428993 | ||
http://www.nsaids-list.com/2012/07/25/ibuprofen-may-help-prevent-parkinsons-disease/ | http://www.nsaids-list.com/2012/07/25/ibuprofen-may-help-prevent-parkinsons-disease/ | ||
http://www.sciencedirect.com/science/article/pii/S0304394004013722 see also apigenin. | http://www.sciencedirect.com/science/article/pii/S0304394004013722 see also apigenin. | ||
− | http://www.als.net/forum/yaf_postst53590_Ibuprofen.aspx | + | http://www.als.net/forum/yaf_postst53590_Ibuprofen.aspx |
− | |||
− | |||
− | |||
− | |||
− | |||
+ | 17. Peony root http://www.als.net/forum/yaf_postst48193_Peony-root-and-paeoniflorin-long-essay.aspx http://www.als.net/forum/yaf_postst53592_Licorice.aspx | ||
+ | Peony is usually taken with non-DG licorice, which enhances its effects. Two anecdotal reports here of benefit, good underlying science. Usually thought of in terms of HSP up-regulation, peony is also a sodium channel inhibitor, which makes it a promising therapeutic for lower motor neuron disease particularly: see Persevering's "Fasciculations" thread. | ||
− | = | + | 18. Resveratrol + nicotinamide NOTE: nicotinamide = niacinamide. http://en.wikipedia.org/wiki/Nicotinamide http://en.wikipedia.org/wiki/Resveratrol |
+ | Check your B-complex vitamin for its niacinamide content (if any). For more detailed discussion regarding this combo, see the paragraph below on "Nicotinamide riboside + resveratrol". WARNING: if you're taking riluzole, be aware that resveratrol and several other natural substances may increase the toxicity of riluzole. I'd argue that if you're doing things that make sense, you shouldn't be taking riluzole anyhow. ......See also the thread http://www.als.net/forum/yaf_postsm384855_Resveratrol-delays-Wallerian-degeneration-in-a-NAD-and-DBC1-dependent-manner.aspx wherein we discuss ideal dosing of resveratrol and come to a tentative conclusion that the customary high dosages found in most supplements nowadays are inappropriate, and that dosage should probably not exceed more than several tens of milligrams. Another link supporting the assertion that high doses are a bad idea: http://www.resveratrolnews.com/how-modern-medicine-obfuscates-resveratrol-science/833/ | ||
+ | |||
+ | CANDIDATES FOR ADDITION TO THE LIST | ||
The following are under consideration for addition to the list. Of course nobody needs my permission to go ahead and decide on their own to take them! ....The ones I regard as most promising (based on what I think I know at the moment) are at the top of the list, less promising stuff on the bottom. | The following are under consideration for addition to the list. Of course nobody needs my permission to go ahead and decide on their own to take them! ....The ones I regard as most promising (based on what I think I know at the moment) are at the top of the list, less promising stuff on the bottom. | ||
− | + | Gastrodin | |
http://www.als.net/forum/yaf_postst53416_Gastrodin.aspx | http://www.als.net/forum/yaf_postst53416_Gastrodin.aspx | ||
− | + | Ethyl alcohol (the beverage kind) | |
http://www.als.net/forum/yaf_postst52660_ethyl-alcohol-booze.aspx | http://www.als.net/forum/yaf_postst52660_ethyl-alcohol-booze.aspx | ||
http://www.news-medical.net/news/20120813/ALS-risk-markedly-lower-among-alcohol-consumers.aspx Glutamate antagonist, GABA agonist, synergistic with glycine. "Candy is dandy but liquor is quicker", you'll know real soon if it provides symptomatic relief for you, plus it's cheap and needs no Rx. Epidemiological study showed drinkers are only half as likely to develop ALS as non-drinkers: the benefit would presumably extend to reduced rate of progression among those who get ALS anyhow. ......WARNING: Too much booze can be bad for you, I hope everyone knows that. Plus, some people readily become addicted to the stuff, which probably results from upregulation of NMDA receptors which would be a bad thing in ALS. So-- I'm not recommending getting smashed every day; and, if you have a family history of alcohol addiction, alcohol may be bad medicine for you. As I sometimes say, "Some people should drink, and some people shouldn't." It's up to you to figure out which category you're in. .......If you drink on a daily basis, it's a good idea to quit cold turkey for a week every now and then. Some people will experience withdrawal symptoms and others won't. If you experience withdrawal symptoms, probably the best thing to do is to taper off the drinking over a period of several weeks in order to detox without landing in the hospital, and thereafter don't touch the stuff. (Yep, I know this is contrary to AA dogma.)........ Going on a ketogenic diet? Sorry, the liver metabolizes alcohol into glucose, that's gonna work against you. .......If you drink, quaff a few pints (not all at once!) to support ALS research, no I'm not kidding: http://www.alesforals.com/ Since this is all about the hops, some pretty good IPA's are likely to come out of that project. | http://www.news-medical.net/news/20120813/ALS-risk-markedly-lower-among-alcohol-consumers.aspx Glutamate antagonist, GABA agonist, synergistic with glycine. "Candy is dandy but liquor is quicker", you'll know real soon if it provides symptomatic relief for you, plus it's cheap and needs no Rx. Epidemiological study showed drinkers are only half as likely to develop ALS as non-drinkers: the benefit would presumably extend to reduced rate of progression among those who get ALS anyhow. ......WARNING: Too much booze can be bad for you, I hope everyone knows that. Plus, some people readily become addicted to the stuff, which probably results from upregulation of NMDA receptors which would be a bad thing in ALS. So-- I'm not recommending getting smashed every day; and, if you have a family history of alcohol addiction, alcohol may be bad medicine for you. As I sometimes say, "Some people should drink, and some people shouldn't." It's up to you to figure out which category you're in. .......If you drink on a daily basis, it's a good idea to quit cold turkey for a week every now and then. Some people will experience withdrawal symptoms and others won't. If you experience withdrawal symptoms, probably the best thing to do is to taper off the drinking over a period of several weeks in order to detox without landing in the hospital, and thereafter don't touch the stuff. (Yep, I know this is contrary to AA dogma.)........ Going on a ketogenic diet? Sorry, the liver metabolizes alcohol into glucose, that's gonna work against you. .......If you drink, quaff a few pints (not all at once!) to support ALS research, no I'm not kidding: http://www.alesforals.com/ Since this is all about the hops, some pretty good IPA's are likely to come out of that project. | ||
− | + | Nicotinamide riboside plus resveratrol | |
+ | http://www.als.net/forum/yaf_postst53368_Nicotinamide-riboside-NR.aspx | ||
+ | http://www.als.net/forum/yaf_postst53465_What39s-the-take-on-NADH.aspx | ||
+ | http://www.als.net/forum/yaf_postst53532_NAD-nicotinamide-adenine-dinucleotide-available-to-reserve-now-by-Biotivia.aspx | ||
+ | see also http://www.als.net/forum/yaf_postsm384855_Resveratrol-delays-Wallerian-degeneration-in-a-NAD-and-DBC1-dependent-manner.aspx#384855 | ||
Looks fairly promising, see especially the -NR thread. The related Nicotinamide is also worth investigation. The related NADH is so far looking like something we do not want to take. Although resveratrol seems to be the most popular candidate as a co-factor for NR, other molecules such as fisetin and even telmisartan have been proposed. NOTE: both theory and anecdotal reports indicate that NR should not be taken without a suitable co-factor. | Looks fairly promising, see especially the -NR thread. The related Nicotinamide is also worth investigation. The related NADH is so far looking like something we do not want to take. Although resveratrol seems to be the most popular candidate as a co-factor for NR, other molecules such as fisetin and even telmisartan have been proposed. NOTE: both theory and anecdotal reports indicate that NR should not be taken without a suitable co-factor. | ||
− | + | Baicalin (Baical Skullcap extract) Complex interactions (apparently mostly favorable) in molecular pathways involved in ALS. http://www.als.net/forum/yaf_postst52727_Baicalin.aspx http://examine.com/supplements/Scutellaria+baicalensis/ | |
− | + | Idebenone Synthetic analogue of CoQ10 said to be much improved over the natural stuff. It'd be on "the list" except that its commercial availability has diminished probably due to harassment by the FDA. | |
− | + | Creatine (long history of use in ALS, probably slightly beneficial, but several grams a day are needed) | |
− | + | Forskolin (cAMP agonist, information scattered, use search tool to search cAMP as well as forskolin) http://en.wikipedia.org/wiki/Forskolin UPDATE: there's now a forskolin thread here: http://www.als.net/forum/yaf_postst53906_forskolin-and-cAMP.aspx | |
− | + | Methylcobalamin B12 (methylating agent etc., info scattered, use search tool) | |
− | + | Vinpocetine There was a flurry of interest in it here a year or two ago. Usually thought of as a nootropic, but its sodium channel modulation properties make it of special interest as a prospective LMN therapeutic. Also inhibits degradation of cAMP, a good synergist for use with forskolin and/or methylxanthines if you're shooting the cAMP angle. http://en.wikipedia.org/wiki/Vinpocetine | |
− | + | Magnesium L-threonate | |
http://www.lef.org/magazine/mag2012/feb2012_Novel-Magnesium-Compound-Reverses-Neurodegeneration_01.htm Supposedly gets magnesium past the BBB better than other mag supplements. | http://www.lef.org/magazine/mag2012/feb2012_Novel-Magnesium-Compound-Reverses-Neurodegeneration_01.htm Supposedly gets magnesium past the BBB better than other mag supplements. | ||
− | + | Sex hormone boosters and modulators DHEA, Tribulus, chrysin, natural estrogen and progesterone creams, Pueraria. Note: there is evidence that beta sitosterols (present in saw palmetto, nettle root, and pygeum) displace cholesterol in the formation of nervous tissue and may thus contribute to neurodegeneration. | |
− | + | Green tea extract (popular anti-aging agent, specificity for ALS unclear) | |
− | + | Pomegranite extract (popular anti-aging agent, specificity for ALS unclear) | |
− | + | Fisetin (new but popular anti-aging agent, specificity for ALS unclear) | |
− | + | Lecithin | |
http://en.wikipedia.org/wiki/Lecithin | http://en.wikipedia.org/wiki/Lecithin | ||
http://en.wikipedia.org/wiki/Phosphatidylcholine | http://en.wikipedia.org/wiki/Phosphatidylcholine | ||
Line 89: | Line 97: | ||
"Brain food", I'd rather get mine by eating eggs than popping pills. Mackerel and herring are high in PS (and also in purines if that matters to you for better or for worse). Soy-derived PS lacks the effectiveness of animal source PS; for this reason I don't think much of soy lecithin as a supplement. | "Brain food", I'd rather get mine by eating eggs than popping pills. Mackerel and herring are high in PS (and also in purines if that matters to you for better or for worse). Soy-derived PS lacks the effectiveness of animal source PS; for this reason I don't think much of soy lecithin as a supplement. | ||
− | + | Lion's Mane Mushroom http://www.als.net/forum/yaf_postst53310_Neuroregenerative-potential-of-lion39s-mane-mushroom.aspx | |
− | + | Berberine http://en.wikipedia.org/wiki/Berberine | |
http://www.als.net/forum/yaf_postst48627_Berberine.aspx | http://www.als.net/forum/yaf_postst48627_Berberine.aspx | ||
http://en.wikipedia.org/wiki/Goldenseal (most common herbal source of berberine) | http://en.wikipedia.org/wiki/Goldenseal (most common herbal source of berberine) | ||
Line 97: | Line 105: | ||
Note: There's lots of herbal supplements out there containing small amounts of berberine, but I haven't yet found one that contains berberine at meaningful dosage levels. | Note: There's lots of herbal supplements out there containing small amounts of berberine, but I haven't yet found one that contains berberine at meaningful dosage levels. | ||
− | + | Butyrates HDAC inhibitors http://en.wikipedia.org/wiki/Butyric_acid | |
http://en.wikipedia.org/wiki/Sodium_butyrate | http://en.wikipedia.org/wiki/Sodium_butyrate | ||
http://www.livestrong.com/article/557578-benefits-of-sodium-butyrate/ | http://www.livestrong.com/article/557578-benefits-of-sodium-butyrate/ | ||
Line 104: | Line 112: | ||
NOTE: although butyrate could theoretically be offered as a nutritional supplement, to my knowledge it's available only as Rx medications. | NOTE: although butyrate could theoretically be offered as a nutritional supplement, to my knowledge it's available only as Rx medications. | ||
− | + | Gardenia extract mitochondrial UCP2 agonist | |
http://www.als.net/forum/yaf_postst52984_Gardenia-jasmoides-extract.aspx#370971 | http://www.als.net/forum/yaf_postst52984_Gardenia-jasmoides-extract.aspx#370971 | ||
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3699730/ | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3699730/ | ||
− | + | Apigenin anti-inflammatory, anti-gliosis. See also ibuprofen. | |
http://www.sciencedirect.com/science/article/pii/S0304394004013722 | http://www.sciencedirect.com/science/article/pii/S0304394004013722 | ||
http://en.wikipedia.org/wiki/Apigenin | http://en.wikipedia.org/wiki/Apigenin | ||
http://www.swansonvitamins.com/swanson-ultra-apigenin-50-mg-90-caps | http://www.swansonvitamins.com/swanson-ultra-apigenin-50-mg-90-caps | ||
− | + | Luteolin closely related to apigenin and more widely available as a supplement. | |
− | + | Vitamin B-1 thiamine, benfotiamine If this makes it into the Prole Prote Toplist, it'll probably be as benfotiamine. | |
http://www.als.net/forum/yaf_postst44708_Foot-drop-and-thiamine.aspx | http://www.als.net/forum/yaf_postst44708_Foot-drop-and-thiamine.aspx | ||
Note: anecdotal report of benfotiamine toxicity, second post in the following thread: | Note: anecdotal report of benfotiamine toxicity, second post in the following thread: | ||
http://www.als.net/forum/yaf_postst49223_Melanin-and-Vitiligo.aspx#334751 This was at high dosage, same patient chose to continue benfotiamine at a more moderate dosage. | http://www.als.net/forum/yaf_postst49223_Melanin-and-Vitiligo.aspx#334751 This was at high dosage, same patient chose to continue benfotiamine at a more moderate dosage. | ||
− | + | Nutritional supplements, herbs, and OTC's rejected for Proletariat Protocol: | |
− | |||
NOTE: This category does not mean the item is "bad", it only means that it seemed worthy of consideration, I did consider it, and regarded it as unsuited for the Proletariat Protocol. | NOTE: This category does not mean the item is "bad", it only means that it seemed worthy of consideration, I did consider it, and regarded it as unsuited for the Proletariat Protocol. | ||
− | + | inosine raises uric acid levels,disinhibits neuron repair esp. of axons. Probably worthwhile under careful medical supervision, but the risk of gouty arthritis and/or kidneystones mean it's not for newbies. http://en.wikipedia.org/wiki/Inosine Inosine has been discussed quite a bit here on the forum. | |
− | + | Cannabis and CBD For most patients, cost, quality of the product, and legal obtainability are problems. If the goddamn government would treat it like tobacco or alcohol, it'd be legal, affordable, and you could know what you were buying. US government has patented the use of cannabidiol to treat neurodegenerative diseases (which however wouldn't stop individuals), see http://www.als.net/forum/yaf_postst53669_Patent-6630507.aspx The inventors seem to think that dosing on the order of half a gram a day would be appropriate, but this seems to be extrapolation from in vitro research and so may be highly inaccurate. In the absence of clinical data, actual anecdotal reports would have more relevancy. | |
− | + | Ginseng http://en.wikipedia.org/wiki/Ginseng Although popular, the evidence in its favor is decidedly mixed, and unwanted side effects are common. | |
http://www.als.net/forum/yaf_postst53520_GINSENG-.aspx | http://www.als.net/forum/yaf_postst53520_GINSENG-.aspx | ||
− | + | Ginkgo biloba Like aspirin, the stuff turns many people into "bleeders". (Like me for instance, this isn't just hypothetical.) Ginkgo might have value for someone who pays close attention to its anti-coagulation properties and makes sure they don't get into trouble with the stuff. | |
− | + | Methylene Blue TDP-43 aggregation inhibitor and other interesting actions. Not sold as a nutritional supplement, but available without Rx as a dye used in biological research. Failed in both SOD-1 and TDP-43 fALS mouse models, but that doesn't end interest in the stuff. http://www.als.net/forum/yaf_postst49812_Methylene-Blue.aspx http://www.als.net/forum/yaf_postst52580_Methylene-blue-Salubrinal-Guanabenz-and-Phenazine-were-each-tested.aspx | |
− | + | * * * * PRESCRIPTION DRUGS THAT MIGHT BE WORTH TAKING * * * * * | |
Research carefully both here and on the Internet, any Rx drug before taking it. The Proletariat Protocol is based on the assumption of no Rx drugs (since doctors usually won't cooperate). However, realistically speaking, most patients who are on a do-it-yourself protocol such as the Prole Prote will also taking one or more Rx drugs either with the cooperation of their medical doctor, or without it. The following list is not intended to be a comprehensive list of interesting Rx drugs, but may serve as a place to begin investigation. Those drugs which in my opinion show the most promise I have shown in boldface. BOILERPLATE: I am not endorsing anything on this list. The only drug on this list that I take specifically for ALS is Deprenyl (Jumex), but that doesn't mean anyone else should. I also take Telmisartan for hypertension and occasionally inhaled beta agonists and steroids for COPD. | Research carefully both here and on the Internet, any Rx drug before taking it. The Proletariat Protocol is based on the assumption of no Rx drugs (since doctors usually won't cooperate). However, realistically speaking, most patients who are on a do-it-yourself protocol such as the Prole Prote will also taking one or more Rx drugs either with the cooperation of their medical doctor, or without it. The following list is not intended to be a comprehensive list of interesting Rx drugs, but may serve as a place to begin investigation. Those drugs which in my opinion show the most promise I have shown in boldface. BOILERPLATE: I am not endorsing anything on this list. The only drug on this list that I take specifically for ALS is Deprenyl (Jumex), but that doesn't mean anyone else should. I also take Telmisartan for hypertension and occasionally inhaled beta agonists and steroids for COPD. | ||
− | + | Riluzole (I'll catch hell for even mentioning that stuff!) | |
− | + | Memantine NMDA receptor antagonist (Ca++ channel blocker), also | |
exhibits activity at several other receptors of neurological interest. | exhibits activity at several other receptors of neurological interest. | ||
Clinical trial failed (of course) since it was not cocktailed. | Clinical trial failed (of course) since it was not cocktailed. | ||
http://en.wikipedia.org/wiki/Memantine | http://en.wikipedia.org/wiki/Memantine | ||
− | + | Prozac and other SSRI's (risky if used with other serotonin enhancers) | |
− | + | Tricyclics (risky if used with other serotonin enhancers) | |
− | + | Prednisone and other corticosteroids | |
− | + | Dilantin (phenytoin) sodium channel inhibitor, long history of use | |
as an anti-epileptic drug. http://en.wikipedia.org/wiki/Dilantin | as an anti-epileptic drug. http://en.wikipedia.org/wiki/Dilantin | ||
− | + | Deprenyl (selegiline)and related drugs MAO-B inhibitor; may also | |
inhibit apoptosis in neurons. Widely used to treat Parkinson's. | inhibit apoptosis in neurons. Widely used to treat Parkinson's. | ||
http://en.wikipedia.org/wiki/Selegiline | http://en.wikipedia.org/wiki/Selegiline | ||
Line 163: | Line 170: | ||
http://www.als.net/forum/yaf_postst45697_selegiline-Deprenyl-vs-ciclosporin.aspx | http://www.als.net/forum/yaf_postst45697_selegiline-Deprenyl-vs-ciclosporin.aspx | ||
− | + | Losartan and related drugs | |
− | + | Albuterol and other selective beta agonists | |
− | + | Theophylline and theobromine http://en.wikipedia.org/wiki/Theophylline | |
Theophylline used to be an OTC bronchodilator but was reclassified as an | Theophylline used to be an OTC bronchodilator but was reclassified as an | ||
Rx drug with the popularization of the safer inhaled beta agonist drugs. | Rx drug with the popularization of the safer inhaled beta agonist drugs. | ||
Line 176: | Line 183: | ||
http://en.wikipedia.org/wiki/Caffeine | http://en.wikipedia.org/wiki/Caffeine | ||
− | + | Valproic acid and valproates Sodium channel blocker, | |
HDAC1 inhibitor, possible neuron apoptosis inhibitor. | HDAC1 inhibitor, possible neuron apoptosis inhibitor. | ||
http://en.wikipedia.org/wiki/Valproic_acid | http://en.wikipedia.org/wiki/Valproic_acid | ||
Line 182: | Line 189: | ||
http://www.als.net/ALS-Research/SodiumValproate/ALS-Topics/ | http://www.als.net/ALS-Research/SodiumValproate/ALS-Topics/ | ||
− | + | Ramelteon ("sleeping pill", melatonin agonist) | |
http://www.als.net/forum/yaf_postst53582_Rozerem-ramelteon.aspx | http://www.als.net/forum/yaf_postst53582_Rozerem-ramelteon.aspx | ||
− | + | Copper chelating agents | |
− | + | Benzodiazepides | |
− | + | Brintellix (Vortioxetine) new antidepressant different from the oldies, acts on a number of different types of serotonin receptors, Jason (jchexpress) reports definite improvement in motor neuron symptoms. http://en.wikipedia.org/wiki/Vortioxetine | |
− | + | Quinidine (often used in conjunction with dextromethorphan) | |
− | + | B12 injection | |
− | + | Acamprosate NMDAr antagonist, GABA agonist, used to suppress alcohol withdrawal. | |
http://en.wikipedia.org/wiki/Acamprosate | http://en.wikipedia.org/wiki/Acamprosate | ||
− | + | Gabapentin (Neurontin) GABA agonist, although its pharmacology | |
is poorly understood. http://en.wikipedia.org/wiki/Gabapentin | is poorly understood. http://en.wikipedia.org/wiki/Gabapentin | ||
WARNING: http://www.wellnessresources.com/main/printable/neurontin_and_lyrica_are_a_death_sentence_for_new_brain_synapses/#ref1 | WARNING: http://www.wellnessresources.com/main/printable/neurontin_and_lyrica_are_a_death_sentence_for_new_brain_synapses/#ref1 | ||
− | + | Pregabalin (Lyrica) GABA agonist closely related to gabapentin, | |
Schedule V drug in the USA. http://en.wikipedia.org/wiki/Pregabalin | Schedule V drug in the USA. http://en.wikipedia.org/wiki/Pregabalin | ||
WARNING: http://www.wellnessresources.com/main/printable/neurontin_and_lyrica_are_a_death_sentence_for_new_brain_synapses/#ref1 | WARNING: http://www.wellnessresources.com/main/printable/neurontin_and_lyrica_are_a_death_sentence_for_new_brain_synapses/#ref1 | ||
− | + | Baclofen GABA-B agonist often used to control cramps and spasms, but | |
once you're on it, stopping is difficult due to withdrawal syndrome. | once you're on it, stopping is difficult due to withdrawal syndrome. | ||
http://en.wikipedia.org/wiki/Kemstro (that link looks wrong but works) | http://en.wikipedia.org/wiki/Kemstro (that link looks wrong but works) | ||
− | + | Naltrexone (low dose protocol) | |
− | + | Edaravone (MCI-186) powerful nervous system antioxidant | |
http://en.wikipedia.org/wiki/Edaravone | http://en.wikipedia.org/wiki/Edaravone | ||
− | + | Mexiletine (sodium channel inhibitor) | |
http://en.wikipedia.org/wiki/Mexiletine | http://en.wikipedia.org/wiki/Mexiletine | ||
http://blogs.als.net/post/Mexiletine-channeling-ALS.aspx | http://blogs.als.net/post/Mexiletine-channeling-ALS.aspx | ||
http://blogs.als.net/post/2013/03/14/Taming-the-Charley-Horse.aspx | http://blogs.als.net/post/2013/03/14/Taming-the-Charley-Horse.aspx | ||
− | + | Ivermectin (AMPA antagonist?) | |
http://en.wikipedia.org/wiki/Ivermectin | http://en.wikipedia.org/wiki/Ivermectin | ||
http://www.als.net/forum/yaf_postst50414_Ivermectin.aspx | http://www.als.net/forum/yaf_postst50414_Ivermectin.aspx | ||
− | + | Retigabine and Flupirtine (Potassium channel openers) | |
http://en.wikipedia.org/wiki/Flupirtine | http://en.wikipedia.org/wiki/Flupirtine | ||
http://www.als.net/forum/yaf_postsm384498_Retigabine--potassium-channels.aspx#384498 | http://www.als.net/forum/yaf_postsm384498_Retigabine--potassium-channels.aspx#384498 | ||
− | + | Dichloroacetic acid (DCA) This stuff's a chemical, not an approved drug or natural supplement. Looks easy to obtain on the gray market. A lot of excitement over its purported anti-cancer benefits, including in neuroblastomas. | |
http://thedcasite.com/ | http://thedcasite.com/ | ||
http://en.wikipedia.org/wiki/Dichloroacetic_acid | http://en.wikipedia.org/wiki/Dichloroacetic_acid | ||
− | + | Prescription drugs and related OTC's etc. to avoid in ALS | |
− | + | Statins (unless supplementing generously with CoQ10) This includes Red Yeast Rice, a natural source of lovastatin. | |
− | + | Anticholinergic antihistamines (including non-Rx OTC's) | |
− | + | Retinoids (related to vitamin A) | |
− | Drugs or supplements containing | + | Drugs or supplements containing copper |
− | Drugs or supplements intended for supplementing | + | Drugs or supplements intended for supplementing iron, unless for the purpose of correcting a diagnosed iron deficiency |
− | Arguably the GABA agonists | + | Arguably the GABA agonists Neurontin and Lyrica: http://www.wellnessresources.com/main/printable/neurontin_and_lyrica_are_a_death_sentence_for_new_brain_synapses/#ref1 |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | + | * * * * * OTHER PROTOCOLS WORTHY OF MENTION HERE * * * * * * * | |
− | + | Dr. Kathy Graham's commentary and critique of the Prole Prote: | |
http://drkathygraham.com/2014/03/19/als-treatments-part-4/#more-1645 | http://drkathygraham.com/2014/03/19/als-treatments-part-4/#more-1645 | ||
She's a physician naturopath in BC Canada who lost her mother to ALS a few years back, hence her interest in ALS. Some of her critique is a little off-base, in part because she was working with an early version of the Prole Prote, and because I'm not sure she fully understood what it is and what it isn't. However, some of it is definitely worth some investigation, for example her low opinion of curcumin and her high opinion of boswellia and berberine. Kinda sounds like she wants to be done with ALS now, but I sure wish we could get her posting here! | She's a physician naturopath in BC Canada who lost her mother to ALS a few years back, hence her interest in ALS. Some of her critique is a little off-base, in part because she was working with an early version of the Prole Prote, and because I'm not sure she fully understood what it is and what it isn't. However, some of it is definitely worth some investigation, for example her low opinion of curcumin and her high opinion of boswellia and berberine. Kinda sounds like she wants to be done with ALS now, but I sure wish we could get her posting here! | ||
− | + | 2004 LEF "Yellow Book" ALS Protocol This publication revolutionized DIY ALS therapeutics a decade ago. I regard the new 2014 "Blue Book" revision as inferior because of its emphasis on the drug pipeline rather than on DIY now. | |
− | + | Chelation Protocols The emphasis used to be on lead and/or mercury, but the attention has recently shifted to copper. I have a low opinion of protocols based on amalgam dental work: supplementing with selenium helps to protect against mercury toxicity. | |
− | + | Ketogenic diet In my opinion, it's valuable for athlete patients, and for non-athlete patients who are losing a lot of muscle mass. Lots of discussion here on the ALSTDI forum. I don't do it myself and haven't researched it well enough to integrate it into the Proletariat Protocol. | |
− | + | Anti-catabolic therapy Note how much this has in common with ketogenic protocols. | |
Possibly a better approach than what we presently think of as ketogenic protocols? http://www.lef.org/protocols/health_concerns/catabolic_wasting_01.htm | Possibly a better approach than what we presently think of as ketogenic protocols? http://www.lef.org/protocols/health_concerns/catabolic_wasting_01.htm | ||
http://en.wikipedia.org/wiki/Glutamine | http://en.wikipedia.org/wiki/Glutamine | ||
− | + | Deanna Protocol This is a general purpose throw-everything-at-it protocol which began as a personal protocol so complex that it was almost impossible for mere mortals to replicate. DP fans are trying hard to simplify the thing to make it easier for mere mortals to do. Philosophically it's traceable to the 2004 LEF "Yellow Book". I predict that as both the Deanna and Proletariat protocols evolve, there will be some tendency toward convergence. There's already quite a bit of overlap. | |
− | + | Mitochondrial Disease Protocol "Mitochondrial Diseases" can be loosely described as diseases caused by defects in mitochondria. Defective mitochondria play a key role in ALS, although defective mitochondria are not usually believed to be the root cause of the disease. However since ALS is many diseases, it's entirely possible that some ALS is a type of mitochondrial disease. The United Mitochondrial Disease Foundation obviously thinks so: http://www.umdf.org/site/pp.aspx?c=8qKOJ0MvF7LUG&b=8032195 A number of therapeutics have been developed for treatment of mitochondrial disease, the United Mitochondrial Disease Foundation's list of which I've named "the Mitochondrial Disease Protocol" although it is actually a shopping list and not specific protocol as such. http://www.umdf.org/site/pp.aspx?c=8qKOJ0MvF7LUG&b=7934635 Notice how much similarity there is between that "protocol" and what we bandy about in relation to motor neuron disease! Also notice that the UMDF has actually published such a list: where are the much larger ALS organizations doing the same? In ALS, it's patients and freelance medical doctors who are working on protocols. | |
− | + | The Ultimate Ducktail Back in Nov 2010, I proposed this therapeutic cocktail based on a fairly short list of carefully targeted "pills". I don't know if anyone ever used it as the basis of their own personal cocktail. If you have access to prescription drugs it's still worth a look. http://www.als.net/forum/yaf_postsm327843_The-Ultimate-Ducktail.aspx#327843 | |
− | + | The Olly ADAR2 Protocol http://www.als.net/forum/yaf_postst53503p4_Gene-therapy-of-Tokyo-University-for-Sporadic-ALS-additional-information.aspx See page 4, post 3 Feb 2014. A work in progress, here's a glimpse: .....Olly wrote: Correcting declining ADAR2 seems to be the better of several other approaches so I'll start there. First a list of possible therapeutic substances followed by a very simple explanation of why they may work. In no particular order: IP6 - Inositol Hexakisphosphate - a cheap ready available supplement. 5-HTP - a cheap ready available supplement but can be dangerous if mixed with certain drugs causing serotonin overdosing. You may want to take B6 -daily amount only - as 5-HTP requires B6 to function. Thiamine (Vitamin B1) High fat diet Selective Anti-depressant/s | |
− | + | Anti-copper protocol This is a project led by fellow forum denizens jchexpress and inventor2, based on the theory that in many ALS patients, a key component of the disease process is misregulation of copper resulting in copper toxicity, having some similarity to Wilson's Disease. Stay tuned to their posts here, this could be a biggie. | |
− | + | Jock Science I love hiking in the desert mountains, and researched the DIY sports medicine literature for ways to temporarily extend my physical abilities and to recover quickly after serious hikes. My ability to go hiking seems to be gone now, but for several years the effectiveness of "jock science" made a huge difference in my life. ...To my knowledge, I'm the only PALS doing "jock science", probably because most PALS have progressed to a point where there's not much left to apply "jock science" to. It's also another pile of stuff that you have to do your own research and get it figured out for yourself. | |
− | + | Cannabis Otherwise known as "marijuana". Many ALS patients, including people who never thought they'd smoke weed, engage in cannabis therapy because it works for themin the area of symptom relief, both upper and lower motor neuron symptoms. It probably slows disease progression as well. Cannabis is arguably the single most useful therapeutic available for ALS, but it's mostly illegal. ....... Cannabis is actually two different pharmaceuticals, THC and its relatives (psychoactive) and CBD (not psychoactive). Both are valuable drugs but their pharmacology is different, and how they impact neurological symptoms and disease processes is only beginning to be unraveled. .......Since CBD is not psychoactive, the legalities surrounding it are less complicated. Dixie Botanicals (located in Colorado) has decided that CBD isn't even a controlled substance and has begun marketing it nationwide. I'd have put it on the Proletariat Protocol list except that the stuff costs several hundred bucks a month, that's not proletariat pricing. I suppose that in another couple years the price will come 'way down. NOTE: Echinacea also contains (non-psychoactive) cannibinoids and might have therapeutic value in ALS: however there seems to be very little research on this. | |
− | + | Anaesthetics Propofol is reported to have helped several ALS patients, but it has to be administered by an anaesthesiologist in a clinical setting. Just about the only way to DIY is to decide that you need a routine colonoscopy and hope you can get the anaesthesiologist to follow your instructions. | |
− | + | Chlorite therapy This is a do-it-yourself project. To do it, it helps if you know a thing or two about chemistry. Several patients have reported benefit. It's not clear how the stuff actually works. | |
− | So-called | + | So-called "Stem Cell" therapies These have been going on for decades for many diseases, and have produced virtually nothing. In ALS, there are a few isolated poorly documented reports of some benefit in bulbar and upper motor neuron disease, but even those (if real) are almost certainly a temporary result of the procedure itself and not of new neurons replacing dead ones. And forget LMN's, that'll never happen. .....There is some genuine stem cell research going on, but the field is rife with incompetency and outright fraud because there's so much popular press hype aimed at gullibillies, creating flocks ready to be fleeced. ......If you are being tempted by a stem cell clinic, first vet it here in this forum and on ALSUntangled. |
− | + | Therapeutic regime targeted to lower motor neuron disease | |
http://www.als.net/forum/yaf_postst49311_Are-Fasciculations-Good-or-Bad.aspx | http://www.als.net/forum/yaf_postst49311_Are-Fasciculations-Good-or-Bad.aspx | ||
For most ALS patients, it looks like loss of the neuromuscular junction is the major driver of physical disability and of maintaining the neurodegenerative cascade. Unfortunately most of what we think we know about treating neurodegenerative disease is borrowed from biggies like stroke and Alzheimer's which don't involve lower motor neurons. We need a therapeutic regime targeted to the lower motor neurons, and the Fasciculations thread seems to contain enough information to at least get us pointed in the right direction: see also Aketri's "ALS theories summary" thread. ...We're making some progress on identifying promising LMN therapeutics and eventually an LMN protocol will probably be integrated into the Proletariat Protocol. | For most ALS patients, it looks like loss of the neuromuscular junction is the major driver of physical disability and of maintaining the neurodegenerative cascade. Unfortunately most of what we think we know about treating neurodegenerative disease is borrowed from biggies like stroke and Alzheimer's which don't involve lower motor neurons. We need a therapeutic regime targeted to the lower motor neurons, and the Fasciculations thread seems to contain enough information to at least get us pointed in the right direction: see also Aketri's "ALS theories summary" thread. ...We're making some progress on identifying promising LMN therapeutics and eventually an LMN protocol will probably be integrated into the Proletariat Protocol. | ||
− | + | Therapeutic regimes targeted to specific types of ALS There is scattered here and in other places, information on the biological differences between the different types of ALS, which implies specifically targeted therapeutics are needed. It is my goal to be able to flesh out the Proletariat Protocol with those kinds of targeted therapeutics, but that's probably going to take at least several months, possibly years inasmuch as the data we have to work with is so little, so fragmented, and in many cases contradictory. ....We do however have the beginnings of such an approach with DM already on the list being targeted particularly to bulbar symptoms, and the ongoing work on LMN targeted therapeutics which is beginning to be pulled into the Proletariat Protocol. | |
+ | |||
+ | Protocols targeting sex hormone levels Scattered through the forum is a lot of information relating to the possible influence of sex hormones on motor neuron disease, but it's never been collected all into one place for a good overview. There was a good thread recently on progesterone. | ||
+ | |||
+ | Over the years, on this information, I've performed using the grey matter meat-technology CPU, a decimate-integrate-and-dump operation. What comes out of that particular information processing pipeline is this: | ||
+ | |||
+ | 1. Reduced hormone levels increase risk of developing ALS, and this is one reason why age and sex are such important ALS demographics. | ||
+ | |||
+ | 2. It's not just one hormone, it's all of 'em-- testosterone, estrogens, and progesterone. | ||
+ | |||
+ | 3. Probably the easiest way to raise hormone levels in a relatively balanced way, is to supplement with DHEA. | ||
− | ' | + | 4. There's a lot of angles to consider: hormones in OTC-supplement form, Rx hormones, tribulus, puereria, epimedium, anti-aromatase, finasteride, minoxidil, vitex, beta sitosterols, etc. |
− | + | 5. But not to make it sound too dangerous or complicated, this is ALS we're dealing with, not acne! Doing nothing has a solid track record of poor outcomes, whereas we're not all dying like flies from overdoses of nutritional supplements. Therefore in my opinion (nonprofessional, your mileage may differ, etc.) if you're into serious ALS therapeutics and over 50 years of age, supplementing with 100 mg a day of DHEA is a good place to begin targeting hormone levels. Preferably getting hormone levels tested occasionally, and preferably staying current on the subject and changing your approach if warranted based on new or additional information. | |
− | |||
− | |||
− | |||
− | |||
Guys, pay attention to possible BPH. The traditional supplement fix for that is beta sitosterol plant extracts, which however may possibly represent a long-term risk of neurotoxicity (information on that is rather sparse, sorry!). There's other stuff like chrysin and pollen extract and boswellia which however don't have as solid a track record in treating BPH as beta sitosterol does. | Guys, pay attention to possible BPH. The traditional supplement fix for that is beta sitosterol plant extracts, which however may possibly represent a long-term risk of neurotoxicity (information on that is rather sparse, sorry!). There's other stuff like chrysin and pollen extract and boswellia which however don't have as solid a track record in treating BPH as beta sitosterol does. | ||
− | The | + | The OFF-LABEL PROTOCOL http://www.als.net/forum/yaf_postst53854_The-OFFLABEL-PROTOCOL.aspx This thread is intended to develop a protocol based on a mix of Rx drugs prescribed off-label, and herbal and nutritional supplements. So far (17 May 2014) unfortunately not much has happened in that thread. |
− | + | * * * * * * | |
− | + | REFERENCES AND RESOURCES | |
Line 379: | Line 371: | ||
ALSTDI has embarked on a research project that integrates genome analysis with in- vitro "drug trials" on tissue samples. This is a revolutionary technology, we're very fortunate to have something like this going on with ALS. Most diseases that aren't in the top 10 get very little research. ........ It'd be easy to explain the expected long-term benefits from this research project, but unlike most research this one stands a chance of benefitting a few PALS while they're still alive. How? If you have a list of your genetic abnormalities, that provides clues to potential therapeutics that may already be available. An obvious example is that if you've got genetic abnormalities known to be associated with dysregulation of copper, you probably really oughta be taking zinc. 2014 was a landmark year, the year we began to develop therapeutic protocols targeted to different types of ALS. On this very forum. It looks like 2015 will also be a landmark year, the year in which genome sequencing finally becomes relevant to therapeutics. Thanks to ALSTDI. | ALSTDI has embarked on a research project that integrates genome analysis with in- vitro "drug trials" on tissue samples. This is a revolutionary technology, we're very fortunate to have something like this going on with ALS. Most diseases that aren't in the top 10 get very little research. ........ It'd be easy to explain the expected long-term benefits from this research project, but unlike most research this one stands a chance of benefitting a few PALS while they're still alive. How? If you have a list of your genetic abnormalities, that provides clues to potential therapeutics that may already be available. An obvious example is that if you've got genetic abnormalities known to be associated with dysregulation of copper, you probably really oughta be taking zinc. 2014 was a landmark year, the year we began to develop therapeutic protocols targeted to different types of ALS. On this very forum. It looks like 2015 will also be a landmark year, the year in which genome sequencing finally becomes relevant to therapeutics. Thanks to ALSTDI. | ||
− | + | Short Essay: ALS Fads The field of ALS therapeutics goes through fad cycles. I'm constantly tweaking my therapeutic regime based on what people are posting about that sounds interesting at the time. .....What gets forum action doesn't necessarily have anything to do with the merit of the stuff in question. It can have to do with availability of information about the stuff, with availability of the stuff itself, or with reports from PALS of supposed benefit or lack of benefit. ....Several years ago, lithium was all the rage: that probably won't happen again with lithium. Nowadays, DM is at the top of my Proletariat Protocol list: it was clinically trialed 'way back when and the results were evidently bowdlerized, the whole time it was a well known NMDA receptor inhibitor, and here we are with the stuff in clinical trial again and more useful information coming from DIY'ers than out of the clinical trial. ........As an ALS patient researching potentially useful therapeutics, you've got a huge pile of possibilities to choose from and not much time to decide and act. I can't tell you to stick with the stuff that's proven, because the only protocol that meets the criterion of proof is the do-nothing protocol and I don't like what it proves. ..... So, I don't discourage newbies from trying stuff that may not have won any popularity contests here. What interests you might be something new (like Gastrodia)or something old that somehow failed to trigger excitement (ibuprofen?). If it looks affordable and safe and the evidence in its favor dials your number, have at it! Sure beats "placebo therapy"! | |
− | The field of ALS therapeutics goes through fad cycles. I'm constantly tweaking my therapeutic regime based on what people are posting about that sounds interesting at the time. .....What gets forum action doesn't necessarily have anything to do with the merit of the stuff in question. It can have to do with availability of information about the stuff, with availability of the stuff itself, or with reports from PALS of supposed benefit or lack of benefit. ....Several years ago, lithium was all the rage: that probably won't happen again with lithium. Nowadays, DM is at the top of my Proletariat Protocol list: it was clinically trialed 'way back when and the results were evidently bowdlerized, the whole time it was a well known NMDA receptor inhibitor, and here we are with the stuff in clinical trial again and more useful information coming from DIY'ers than out of the clinical trial. ........As an ALS patient researching potentially useful therapeutics, you've got a huge pile of possibilities to choose from and not much time to decide and act. I can't tell you to stick with the stuff that's proven, because the only protocol that meets the criterion of proof is the do-nothing protocol and I don't like what it proves. ..... So, I don't discourage newbies from trying stuff that may not have won any popularity contests here. What interests you might be something new (like Gastrodia)or something old that somehow failed to trigger excitement (ibuprofen?). If it looks affordable and safe and the evidence in its favor dials your number, have at it! Sure beats "placebo therapy"! | ||
+ | WARNING ABOUT RILUZOLE | ||
+ | Olly wrote: | ||
− | + | ||
− | The word is bandied about here as though it actually meant something important. Sure sounds important when the topic is ALS. | + | |
+ | Neurodegener Dis. 2013 Dec 20. [Epub ahead of print] | ||
+ | The Neuroprotection Exerted by Memantine, Minocycline and Lithium, against Neurotoxicity of CSF from Patients with Amyotrophic Lateral Sclerosis, Is Antagonized by Riluzole. | ||
+ | |||
+ | Abstract | ||
+ | In a recent study we found that cerebrospinal fluids (CSFs) from amyotrophic lateral sclerosis (ALS) patients caused 20-30% loss of cell viability in primary cultures of rat embryo motor cortex neurons. | ||
+ | |||
+ | We also found that the antioxidant resveratrol protected against such damaging effects and that, surprisingly, riluzole antagonized its protecting effects. | ||
+ | |||
+ | Here we have extended this study to the interactions of riluzole with 3 other recognized neuroprotective agents, namely memantine, minocycline and lithium. We found: (1) by itself riluzole exerted neurotoxic effects at concentrations of 3-30 µM; this cell damage was similar to that elicited by 30 µM glutamate and a 10% dilution of ALS/CSF; (2) memantine (0.1-30 µM), minocycline (0.03-1 µM) and lithium (1-80 µg/ml) afforded 10-30% protection against ALS/CSF-elicited neurotoxicity, and (3) at 1-10 µM, riluzole antagonized the protection afforded by the 3 agents. | ||
+ | |||
+ | These results strongly support the view that at the riluzole concentrations reached in the brain of patients, the neurotoxic effects of this drug could be masking the potential neuroprotective actions of new compounds being tested in clinical trials. | ||
+ | |||
+ | Therefore, in the light of the present results, the inclusion of a group of patients free of riluzole treatment may be mandatory in future clinical trials performed in ALS patients with novel neuroprotective compounds. | ||
+ | |||
+ | © 2013 S. Karger AG, Basel. | ||
+ | |||
+ | PMID: 24356417 [PubMed - as supplied by publisher] | ||
+ | |||
+ | |||
+ | Short essay: What does "neuroprotective" mean? The word is bandied about here as though it actually meant something important. Sure sounds important when the topic is ALS. | ||
The list of substances described as "neuroprotective" in the PubMed Pile is almost limitless. Most commonly, a substance is described in this way for one of the following reasons: | The list of substances described as "neuroprotective" in the PubMed Pile is almost limitless. Most commonly, a substance is described in this way for one of the following reasons: | ||
− | + | 1. It inhibited damage or death to neurons in in vitro testing, when the neurons were exposed to some kind of agent known to cause damage to neurons. | |
− | + | ||
+ | 2. In an animal model of stroke or other localized experimentally induced ischemia, the substance reduced death and/or improved recovery. The underlying molecular biology is almost always either modulation of glutamate, or modulation of glutamate receptors. | ||
In the context of ALS therapeutics, this isn't very good news. | In the context of ALS therapeutics, this isn't very good news. |