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Another possible medication for Alzheimer's disease
Lane Simonian
Posted: Monday, November 2, 2015 1:39 PM
Joined: 12/12/2011
Posts: 4998

So here is another tantalizing promise for treating Alzheimer's disease:

Neurocentria Inc., a clinical-stage biopharmaceutical company developing therapeutics to enhance brain function and correct cognitive impairment, announced the successful completion of a human study demonstrating that the company's lead compound significantly reversed cognitive impairment in subjects 50 to 70 years old. The results have been published in the peer-reviewed Journal of Alzheimer's Disease.

The double-blind, placebo-controlled clinical trial demonstrated with high statistical significance (p <0.01) that MMFS-01 improved subjects' overall cognitive ability, as determined by a composite score of tests in four major cognitive domains: executive function, working memory, attention and episodic memory.

Importantly, MMFS-01 improved cognitive function performance seen at baseline, while the majority of human clinical trials for other Alzheimer's drugs under development are focused on slowing down cognitive decline. In addition, it achieved statistical significance in just six weeks of treatment. For comparable drugs, statistical significance has been seen after a much longer timeframe, ranging from 12 to 72 weeks.

The study results have clinical significance. The study measured the "brain age" of subjects based on their executive function performance. The brain age of study participants taking MMFS-01 improved by nine years after six weeks of treatment, and persisted after 12 weeks of treatment. By contrast, participants who received a placebo saw little change in their average brain age. These data demonstrate that MMFS-01 is effective at reversing cognitive deficit. The study also showed that MMFS-01 was well tolerated; all adverse events were of mild severity, and there were a greater number of such events under placebo versus treatment conditions.

MMFS-01 seems to increase synaptic density, but it is unclear exactly what the compound is. Here is a semi-educated guess.

5-(methoxymethyl)furan-2-carbaldehyde (MMF) 

If this is the right guess,  it is interesting because ANAVEX which has also showed promise against Alzheimer's disease is also a furan derivative.

Name: Anavex 2-73
Chemical Name: Tetrahydro-N,N-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride

The key to treating Alzheimer's disease is likely with antioxidants that contain hydroxy and methoxy groups (such as curcumin, eugenol, ferulic acid, syrinigic acid, sinapic acid, and vanillin).  ANAVEX and MMFS-01 seem to come close.

Lane Simonian
Posted: Wednesday, November 25, 2015 10:00 AM
Joined: 12/12/2011
Posts: 4998

Wrong guess.  Neurocentria's compound is L-threonic acid magnesium salt.  This type of compound is being studied for the treatment of Alzheimer's disease, but I have not seen any positive results reported as of yet.
Posted: Wednesday, November 25, 2015 5:39 PM
Joined: 9/12/2013
Posts: 3608

I hope some thing comes out soon. Now that I have settled into having ALZ it would be another shock to RECOVER!

But for my children and grandchildren and everyone else I sure hope something comes along.

Thanks Lane for staying in the mix here. It is a great comfort to know you are working on our behalf.

Lane Simonian
Posted: Friday, November 27, 2015 8:55 AM
Joined: 12/12/2011
Posts: 4998

I appreciate it very much alz+.  I am afraid this compound is likely to help only those in the earliest stages of cognitive impairment, but I will keep looking for the newest developments (as a "protector male"--maybe the term does fit me to a degree).

I hope that you and everyone else here had a good Thanksgiving.

Posted: Saturday, November 28, 2015 6:25 AM
Joined: 4/24/2012
Posts: 484

Interesting  study. I read through it to see if they gave any clues to how the drug may be working. As Lane mentioned, it has to do with magnesium. Specifically, getting magnesium accross the blood-brain barrier so that it can benefit the brain.  Here is the key statement from the study:

"Our pre-clinical work indicates that the mechanism of action of MMFS-01 is increased structural and functional synapse density, mediated by an elevation of neuronal intracellular magnesium concentration [7, 8]."

My translation of this is: "Magnesium deficiency in the brain may be a cause of Alzheimer's.

Mimi S.
Posted: Saturday, November 28, 2015 9:29 AM
Joined: 11/29/2011
Posts: 7027

How early is early diagnosis?

The problem today is that those diagnosed with Younger Onset have the most difficult time getting diagnosed.  Too much time is lost.

And for those of us whose symptoms begin at the normal retirement age, too many physicians, still seem to think this is part of normal aging.   If I had waited until the symptoms mentioned  in the literature became a major part of my life style, I doubt I'd still be around.

Having seen relatives in the midst of the disease, sought help when I first noticed symptoms. Even though I was seeing a neurologist for another disease, she ignored my complaints about increasing memory issues.
Lane Simonian
Posted: Saturday, November 28, 2015 9:34 AM
Joined: 12/12/2011
Posts: 4998

This one is for magnesium in the treatment of glaucoma but glucoama is another disease in which peroxynitrites play an important role.

Magnesium (Mg) is thought to be one of the molecules that has a treatment potential in glaucoma. Mg has been shown to improve blood flow by modifying endothelial function via endothelin-1 (ET-1) and endothelial nitric oxide (NO) pathways. Mg also exhibits neuroprotective role by blocking N-methyl-D-aspartate (NMDA) receptor-related calcium influx and by inhibiting the release of glutamate, and hence protects the cell against oxidative stress and apoptosis. Both improvement in ocular blood flow and prevention of ganglion cell loss would make magnesium a good candidate for glaucoma management. Further studies on the effect of Mg may open a new therapeutic era in glaucoma.

In terms of decreasing oxidative stress, aminoguanidine, an oral insulin stimulant for type 2 diabetes mellitus and a specific inhibitor of inducible nitric oxide synthase (NOS-2), was experimentally shown to prevent the development of GON [14] [glaucomatous optic neuropathy]. Ginkgo biloba extract, an antioxidant polyphenolic flavonoid, has been reported to improve visual field parameters in a double-blinded placebo-controlled study [15]. Ginkgo biloba extract was shown to protect the mitochondria from oxidative stress and thereby might rescue the retinal ganglion cells [16]. Mg may add a therapeutic value in the field of glaucoma via similar mechanisms such as improvement in ocular blood flow, reduction of oxidative stress, and neuroprotection.

During reperfusion injury, a high concentration of superoxide radicals and NO results in the formation of highly damaging peroxynitrites, [56] which may lead to retinal ganglion cell loss and GON [2]. 

As cognitive impairment progresses, pairing magnesium (in forms that make it to the brain in larger concentrations) with various antioxidants may be more effective than magnesium alone.

Lane Simonian
Posted: Saturday, November 28, 2015 9:45 AM
Joined: 12/12/2011
Posts: 4998

Even more to the point (perfect translation, Serenoa):


The present study demonstrates that exogenous ONOO- [peroxynitrite] can result in rapid declines in intracellular free magnesium ions ([Mg2+]i) concomitant with rapid rises in intracellular free calcium ions ([Ca2+]i) and, subsequently, trigger apoptosis but not necrosis in rat aortic SMCs [smooth muscle cells]; high [Mg2+] significantly attenuates ONOO--induced apoptosis. ONOO-- induced apoptosis in vascular SMCs appears to involve activation of Ca2+-Mg2+-dependent endonucleases and caspase-3. Mg deficiency itself could not induce apoptosis in these SMCs, but it could significantly enhance ONOO-- induced apoptosis. 

Magnesium deficiency in rats leads to an oxidative stress involving an increased production of radicaloxygen species. The present study was designed to examine the effect of experimental magnesium deficiency on plasma nitric oxide (NO) level and nitric oxide synthases (NOS) activities in rats. The data show that the concentration of NO is markedly increased in plasma of magnesium-deficient rats. This rise in plasma NO results from activation of inducible nitric oxide synthase (iNOS) rather than of the constitutive form (cNOS) of the enzyme. These data are in agreement with previous observations indicating that inflammation occurs during magnesium-deficiency and provide an additional cause of oxidative lesions through formation of peroxynitrite from nitric oxide and superoxide anion.

Posted: Saturday, November 28, 2015 10:55 AM
Joined: 4/24/2012
Posts: 484

Yes. Inflamation, oxidative dammage connections. More evidence in this article:


Hypomagnesemia (Hypo-Mg) in rodents leads to neurogenic inflammation associated with substance P (SP) elevations; neutral endopeptidase (NEP) is a principle cell surface proteolytic enzyme, which degrades SP. The effects of chronic Hypo-Mg on neutrophil NEP activity, cell activation and the associated cardiac dysfunction were examined.


Male Sprague-Dawley rats (180 g) were fed Mg-sufficient or Mg-deficient (Hypo-Mg) diets for five weeks. Enriched blood neutrophils were isolated at the end of one, three and five weeks by step gradient centrifugation. NEP enzymatic activity decreased by 20% (P value was nonsignificant), 50% (P<0.025) and 57% (P<0.01), respectively, for week 1, 3 and 5 Hypo-Mg rats. In association, neutrophil basal superoxide (•O2−)-generating activities were elevated: 30% at week 1 (P value was nonsignificant), and fourfold to sevenfold for weeks 3 to 5 (P<0.01). Maximal phorbol myristate acetate-stimulated •O2− production by Hypo-Mg neutrophils increased twofold at week 5. Also, plasma 8-isoprostane levels were elevated twofold to threefold, and red blood cell glutathione decreased by 50% (P<0.01) after three to five weeks of chronic Hypo-Mg. When Hypo-Mg rats were treated with the SP receptor blocker (L-703,606), neutrophil NEP activities were retained at 75% (week 3) and 77% (week 5) (P<0.05); activation of neutrophil •O2− and other oxidative indexes were also significantly (P<0.05) attenuated. After five weeks, histochemical (hematoxylin and eosin) staining of Hypo-Mg-treated rat ventricles revealed significant white blood cell infiltration, which was substantially reduced by L-703,606. Echocardiography after three weeks of Hypo-Mg only showed modest diastolic impairment, but five weeks resulted in significant (P<0.05) depression in both left ventricular systolic and diastolic functions; changes in these functional parameters were attenuated by L-703,606.


NEP activity regulates neutrophil •O2− formation by controlling SP bioavailability. When oxidative inactivation of NEP is prevented by SP receptor blockade, partial protection is afforded against cardiac contractile dysfunction.

Posted: Saturday, November 28, 2015 10:57 AM
Joined: 4/24/2012
Posts: 484

And this has some clues I think:


This study assessed the changes in the isoprenoid pathway and the consequences of its dysfunction in Alzheimer's disease (AD). The isoprenoid pathway and digoxin status were also studied for comparison in individuals of differing hemispheric dominance to find the role of cerebral dominance in the genesis of Alzheimer's disease. There was elevation in plasma HMG CoA reductase activity, serum digoxin, and dolichol levels, and a reduction in serum magnesium, RBC membrane Na+-K+ ATPase activity, and serum ubiquinone levels. Serum tryptophan, serotonin, strychnine, nicotine, and quinolinic acid were elevated, while serum tyrosine, morphine, dopamine, and noradrenaline were decreased. The total serum glycosaminoglycans and glycosaminoglycan fractions, the activity of GAG degrading enzymes and glycohydrolases, carbohydrate residues of glycoproteins, and serum glycolipids were elevated in Alzheimer's disease. HDL cholesterol was reduced and free fatty acids increased. The RBC membrane glycosaminoglycans, hexose, and fucose residues of glycoproteins and cholesterol were reduced, while phospholipid increased. The activity of all free radical scavenging enzymes, concentration of glutathione, alpha tocopherol, iron binding capacity, and ceruloplasmin decreased significantly in Alzheimer's disease, while the concentration of lipid peroxidation products and NO increased. The hypomagnesemia-related NMDA excitotoxicity, ubiquinone deficiency related mitochondrial dysfunction, and altered glycoconjugates/lysosomal stability could contribute to the pathogenesis of Alzheimer's disease. The biochemical patterns, including hyperdigoxinemia observed in Alzheimer's disease, correlated with those obtained in right hemispheric chemical dominance. Right hemispheric chemical dominance is a predisposing factor for Alzheimer's disease.

Posted: Saturday, November 28, 2015 11:02 AM
Joined: 4/24/2012
Posts: 484

Mimi S. you make a great point. It is common for doctors to ignore symptoms until they get bad enough to warrent treatment by pharmaceuticals or surgery. Prevention-based, patient-centered treatment is rarely valued by Western Medicine. Traditional Chinese Medicine is much better in this respect.
Lane Simonian
Posted: Saturday, November 28, 2015 11:38 AM
Joined: 12/12/2011
Posts: 4998

All excellent finds, Serenoa.  My thinking on this is (in part to relate to Mimi's observation), if you give magnesium threonate supplementation during the first signs of cognitive impariment, you can impede the activation of NMDA receptors and the subsequent production of peroxynitrite.  But if you give it after that, too much of the magnesium has already been displaced.  However, if you combine magnesium threonate supplementation with a peroxynitrite scavenger than you are killing one bird (NMDA receptor activation) with two stones.

Mimi, I entirely agree with a comment you made on another post: if a person is proactive against Alzheimer's disease they can at least slow down it progression and with the right combination of compounds they can likely partially reverse it.  The idea that nothing has ever slowed down the progression of Alzheimer's disease is not supported by the evidence, and yet it is repeated endlessly in one article after another.  Many people do not even try to be proactive because they have been convinced that there is nothing they can do. 

Thanks all for commenting here.  I remember the old days where so many different people were contributing everything under the sun here.  It was a lively, sometimes contentious forum.  I learned a lot from my mentors, some of whom are thankfully still here. 

Posted: Sunday, November 29, 2015 6:40 AM
Joined: 4/24/2012
Posts: 484

Hypomagnesemia (magnesium deficiency) is implicated and associated with many conditions that have relevance to Alzheimer's. And the experts seem to agree that magnesium deficiency is common in modern diets. The research seems to point to this deficiency as having the ability to cause many illnesses (like cadiovascular disease, insulin resistance, oxidative stress, etc.), and at the same time, these illnesses have the ability to deplete magnesium. Some studies show magnesium deficiency being present in Alzheimer's. Is magnesium deficiency a symptom or a cause of disease? Is it both? And, what is the best way to address it?
Posted: Friday, January 29, 2016 8:44 AM
Joined: 1/25/2016
Posts: 13

Very interesting! I am giving my husband 2 MagMinds (1-magnesium threonate) every night. IS this helpful?  Anyone know how different this drug is from the supplement?

Another question - any thoughts on copper and zinc in the brain.  Some of Rudy Tanzi's work has been on that.  Thoughts?

And he's involved peripherally with another company that is currently testing ibuprofen and an over the counter nasal spray called cromolyn sodium. More thoughts?


The "word" now is that the treatment of the future for ALZ will be a cocktail.