AffiRiS is reporting today research results in which they claim the first drug trial ever to demonstrate both clinical and biomarker effects consistent with disease modification for Alzheimers patients. The results were truly impressive and are important to PwP because they have a similar ongoing study for Parkinson's (funded by MJFF). They will report those results in a few months.

What is startling and confusing, though, about the trial, and not well reported in their press release, is that the substance showing these great statistically significant results was the PLACEBO (AD04), not the actual trial drug being tested (AD02). The results, for the first time ever, met both the FDA and EMA criteria for disease modification. With the use of a biomarker in the hippocampus, they were able to prove that this wasn't just a placebo effect.

Forty-seven percent of those who received AD04 exhibited what the company called "effects consistent with disease modification" for at least 18 months. Moreover, the cessation of disease progression was correlated with a stabilization of hippocampus volumes.

The company doesn't really know why they got the effect as the new "drug" was in no way related to the test drug. They will not even say what the drug is because, at this time, they don't even have a patent on it.

Medical history of accidental major breakthroughs has happened in the past, so this certainly will make us all focus on the PD trial results with great interest.

http://bit.ly/1hghALZ

Here is an interesting take on the announcement. It really gets interesting at #8 in the comments. Apparently, the initial drug, a vaccine, supports other recent studies that indicate beta amyloid (the AD prion) may not be the culprit and may in fact be beneficial. The researcher comments here hint that the mystery compound is an immuno..modulator that functions as a nitrite scavenger.

Good News! Our Alzheimer's Drug didn't Work.

I have run across articles on nitrites in PD. Here is a really interesting one from 2009. It is remarkable to note that the researchers find that increase in death rate from PD and AD was not age related but rather reflective of exposure to food additive nitrosamines that are used as preservatives. I have always felt strongly that our diets play a strong role in etiology, but it really seems understudied.

Nitrates May Be Environmental Trigger For Alzheimer’s, Diabetes And Parkinson's Disease.

Welcome back, Laura!

Conductor71 references comments on the AD work. Comment 8 by Esteban is:
"Or what if the immunomodulator is a peroxynitrite scavenger?"

OK, so the paper is about AD, BUT regarding Parkinson's:

A group in Iran write [1]:

"Our data indicate that elevated serum levels of NO and peroxynitrite have an impact on progression of PD. Levels of NO and peroxynitrite may be considered as biomarkers for PD progression in the future. However, other studies are necessary for definite recommendations."

References:

[1] Eur Rev Med Pharmacol Sci. 2013 Apr;17(7):964-70.
"Nitric oxide and peroxynitrite serum levels in Parkinson's disease: correlation of oxidative stress and the severity of the disease."
Kouti L1, Noroozian M, Akhondzadeh S, Abdollahi M, Javadi MR, Faramarzi MA, Mousavi S, Ghaeli P.
http://www.europeanreview.org/wp/wp-...ds/964-970.pdf

John

There are 9 current paradigms for disease such as infections, genetic mistakes, nutritional deficiencies, hormone dysfunctions, allergies, autoimmune conditions, cellular mutations, ischemic cardiovascular disease and amyloid (prion) diseases. Martin L. Pall Ph.D., in his book, Explaining “Unexplained Illnesses,” proposes a 10th. This paradigm proposes an explanation for such conditions as Chronic Fatigue Syndrome, Fibromyalgia, Multiple Chemical Sensitivity, Post-Traumatic Stress Disorder, and Gulf War Syndrome. He calls these illnesses, “multisystem illnesses.”

In addition, other illnesses may be due wholly or in part to this new paradigm. Among the candidates are tinnitus, post-radiation syndrome, multiple sclerosis, autism, overtraining syndrome, silicone implant associated syndrome, Sudeck’s atrophy, postherpetic neuralgia, chronic whiplash-associated disorder, amyotrophic lateral sclerosis, Parkinson’s disease, and Alzheimer’s disease.

Dr. Pall’s book is quite technical and extensive and most of it is devoted to proving his theory which (very simplified) goes something like this:

Usually, an initial stressor such as infection, trauma, psychological distress, etc. in people genetically disposed to it, increases bodily nitric oxide (NO) production. Through a feedback mechanism, this level of nitric oxide remains high, whereas in those less disposed it returns to normal. High NO levels through many mechanisms cause oxidative stress and mitochondrial damage resulting in the many symptoms related to these illnesses. Since the NO level rise is local, the symptoms depend upon where the malfunction occurs.

Excess NO is acted upon by the free radical superoxide to form peroxynitrite, hence Dr. Pall’s name for his paradigm, the NO/ONOO¯ cycle (pronounced No! Oh No!)

Peroxinitrite is the main bad actor in this play but others are also formed in a rather complicated web of interrelated interactions. If you are interested in sorting out these interactions, how they affect the body, and why these unexplained illnesses can be explained by them, buy the book.

Some of the other results of this web are increases in inflammatory cytokines such as Il-6, Il-8, Il-1β, TNF-α, and INF-γ.

It also causes an increase in NF-κβ, increases in the activity of brain receptors NMDA, and Vanilloid, and increases in the NO synthases that make more NO.

Dr. Pall says there are no magic bullets that return the cycle to normal. It requires attacking each of these biochemical excesses to lower them and to protect and repair the mitochondria, the organelle in the cell that creates energy. In other words, a multimodal approach is needed. This approach should lower NO and peroxinitrate, lower NF-κβ and the inflammatory cytokines, supply powerful antioxidants, and lessen the NMDA and vanilloid receptors.

Based upon his “best guess” list of therapeutic substances and the lists he mentions which are used successful by various physicians, here are the basic nutriceuticals:

1. Glutathione. He recommends inhaled but liposomal may do as well.Acetyl glutathione is probably best.
2. Hydroxycobalamin is a form of Vitamin B12. He recommends inhaled, injected or sublingual forms. He says others such as cyanocobalamin or methylcobalamin will not work as well as NO scavengers.
3. Mixed natural tocopherols, especially the γ-tocopherol form of Vitamin E.
4. Buffered Vitamin C.
5. Magnesium as malate. It is presumed that Krebs cycle forms of magnesium or the addition of Malic acid would also help.
6. Four different forms of flavonoids including Ginkgo biloba, Cranberry, Silymarin, and Bilberry. Better than these (not in the book but endorsed by the doctor) is a form of Brown Kelp called Ecklonia cava.
7. Selenium as selenium grown yeast.
8. Coenzyme Q10.
9. Folic Acid.
10. Carotenoids such as Lycopene,Lutein, and Beta Carotene.
11. Alpha Lipoic Acid.
12. Zinc, Manganese, and Copper (modest dose for zinc and low dose for the others.)
13. Vitamin B6 in the form of Pyridoxyl Phosphate.
14. Vitamin B2 (Riboflavin) as Riboflavin 5’ –phosphate (FMN).
15. Betaine (Trimethylglycine).
16. Taurine.
17. Polyunsatured Phosphatidylcholine.
18. Acetyl-L-Carnitine.
19. Carnosine.
20. SOD.
21. To the book’s list might be added Shrubby Sophora, and Pyrroloquinoline quinone (PQQ).

What all these substances do and the reason for them may be found in the book. It also describes some outcomes from using them.