Worthy of note is the fact that the pale skinned Irish emigrants staggering off the 'Coffin Ships' were dressed in skimpy rags and therefore became badly sunburnt. DNA damage would ensue.

http://en.wikipedia.org/wiki/Coffin_ship

Should the positive results with NP001 be due to the fact that it inhibits G6PD, then monitoring the enzyme in SALS family members may be warranted. Perhaps they could then be placed on a preventative dose.

Mary

http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=362.0

Summary
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common hereditary erythrocyte enzyme deficiency. The deficiency is frequent: it affects 0.5-26% of the population and an estimated 420 million individuals in the world. The Mediterranean region, sub-Saharan Africa, the Americas (African and Hispanic populations) and South-East Asia are the regions most affected.

http://www.atcc.org/ATCCAdvancedCatalogSearch/ProductDetails/tabid/452/Default.aspx?ATCCNum=HTB-128&Template=cellBiology

mixed ancestry as suggested by the presence of G6PD type A phenotype in the cells.

Positive or negative? High blood sugar levels decrease G6PD activity.

http://en.wikipedia.org/wiki/Glucose-6-phosphate_dehydrogenase_deficiency

The high prevalence of diabetes mellitus type 2 and hypertension in Afro-Caribbeans in the West could be directly related to the incidence of G6PD deficiency in those populations

Eur J Neurol. 2010 May;17(5):733-9. Epub 2010 Jan 13.
ALS disease onset may occur later in patients with pre-morbid diabetes mellitus.
Jawaid A, Salamone AR, Strutt AM, Murthy SB, Wheaton M, McDowell EJ, Simpson E, Appel SH, York MK, Schulz PE.
Source
Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.

Abstract
BACKGROUND:
Several metabolic derangements associated with diabetes mellitus type 2 (DM) have been associated with a better outcome in amyotrophic lateral sclerosis (ALS), including hyperlipidemia and obesity. Here, we tested the hypothesis that DM would have a positive effect on the motor and cognitive findings of ALS.

METHODS:
We compared data from ALS patients with pre-morbid DM (ALS-DM; n = 175) versus without DM (ALS; n = 2196) with regard to the age of onset, rate of motor progression, survival, and neuropsychological test performance.

RESULTS:
The age of onset was later for women, Caucasians and patients with bulbar-onset ALS. However, we also found that after adjusting for gender, ethnicity and site of onset, DM was associated with a 4-year later onset of ALS (ALS = 56.3, ALS-DM = 60.3, P < 0.05).

CONCLUSION:
Diabetes mellitus type 2 may delay the onset of motor symptoms in ALS. These findings support other studies suggesting a relationship between the pathophysiology of ALS and metabolic derangements. Further investigations are needed to ascertain whether manipulating metabolic parameters would improve outcomes in ALS.

PMID:
20074230
[PubMed - indexed for MEDLINE]

Amyotroph Lateral Scler. 2011 Jul;12(4):309-11. Epub 2010 Dec 2.
Hyperosmolar hyperglycemic state in advanced amyotrophic lateral sclerosis.
Shimizu T, Honda M, Ohashi T, Tsujino M, Nagaoka U, Kawata A, Watabe K, Matsubara S, Hayashi H.
Source
Department of Neurology, Tokyo Metropolitan Neurological Hospital , Tokyo.

Abstract
Abstract Our objective was to describe cases of hyperosmolar hyperglycemic state (HHS) in advanced amyotrophic lateral sclerosis (ALS) patients and discuss its pathophysiology. Five ventilator-dependent patients with ALS, with no previous history of diabetes, showed development of marked hyperglycemia (plasma glucose levels of 755-1544 mg/dl) after preceding infectious episodes. All patients had severe generalized muscle wasting and tetraplegia. The initial manifestations of HHS were fever, drowsiness, or polyuria. Hydration and intravenous insulin therapy were markedly effective, resulting in favorable recovery without the necessity of chronic medication for hyperglycemia in all cases. Seventy-five grams oral glucose tolerance tests performed via feeding tubes in two patients after the successful treatment of HHS revealed increased insulin resistance and diminished early-phase insulin secretion with preserved total insulin secretion. In conclusion, a marked loss of skeletal muscle, the largest glucose consumer of the human body, with background abnormality of early-phase insulin secretion, might be a causative factor of HHS in advanced ALS.

PMID:
21126160
[PubMed - in process]
Amyotroph Lateral Scler. 2010;11(1-2):166-71.
Impaired glucose tolerance in patients with amyotrophic lateral sclerosis.
Pradat PF, Bruneteau G, Gordon PH, Dupuis L, Bonnefont-Rousselot D, Simon D, Salachas F, Corcia P, Frochot V, Lacorte JM, Jardel C, Coussieu C, Le Forestier N, Lacomblez L, Loeffler JP, Meininger V.
Source
APHP, Hôpital de la Pitié-Salpêtrière, Fédération des Maladies du Système Nerveux, Paris, France. pierre-francois.pradat@psl.aphp.fr <pierre-francois.pradat@psl.aphp.fr>

Abstract
Our objectives were to analyse carbohydrate metabolism in a series of ALS patients and to examine potential association with parameters of lipid metabolism and clinical features. Glucose tolerance was assessed by the oral glucose tolerance test in 21 non-diabetic ALS patients and compared with 21 age- and sex-matched normal subjects. Lipids and lactate/pyruvate ratio, levels of pro-inflammatory cytokines (tumour necrosis factor-alpha and interleukin-6) and adipocytokines (leptin and adiponectin) were also measured in ALS patients. Mann-Whitney U-tests analysed continuous data and Fisher's exact tests assessed categorical data. Blood glucose determined 120 min after the glucose bolus was significantly higher in patients with ALS (7.41 mmol/l+/-1.68) compared to controls (6.05+/-1.44, p=0.006). ALS patients with impaired glucose tolerance (IGT) according to WHO criteria (n=7, 33%) were more likely to have elevated free fatty acids (FFA) levels compared to patients with normal glucose tolerance (0.77 nmol/l+/-0.30 vs. 0.57+/-0.19, p=0.04). IGT was not associated with disease duration or severity. In conclusion, patients with ALS show abnormal glucose tolerance that could be associated with increased FFA levels, a key determinant of insulin resistance. The origin of glucose homeostasis abnormalities in ALS may be multifactorial and deserves further investigation.

PMID:
20184518
[PubMed - indexed for MEDLINE]

About the subject of this thread: it might be that 93% of PALS in the registry are caucasian because signing up for a disease registry is something that caucasians do, and something that people of other races don't trust.

I believe that the State and Metro surveillance projects that have been added to the scope of the CDC's ALS Registry are meant in part to help make sure that racial and ethnic groups are not being underrepresented by the Registry's data mining algorithm and self-enrollment data.

http://wwwn.cdc.gov/als/ALSStateMetro.aspx

Thanks, DeeBee!

We could do with some more hybrid studies. They get terrible diseases but less often than thoroughbreds.

Both the UK and US are moving rapidly towards hybridization. This could be an example of 'nature finding a way'?

http://www.youtube.com/watch?v=v6OFYrF_9Ao&feature=related

( I'm growing Russian hybrid tomato plants this year that produce huge stunning fruit ).

For DeeBee:

Even zorses and ligers get ALS...

http://www.ncbi.nlm.nih.gov/pubmed/22342397

J Neurol Sci. 2012 Feb 17. [Epub ahead of print]

Clinical aspects of amyotrophic lateral sclerosis in Rio de Janeiro/Brazil.
Loureiro MP, Gress CH, Thuler LC, Alvarenga RM, Lima JM.

Source
Department of Motor Neuron Diseases/Amyotrophic Lateral Sclerosis, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil; Postgraduate Programme in Neurology, Federal University of the State of Rio de Janeiro (UNIRIO), Rio de Janeiro, Brazil.

Abstract
OBJECTIVE:
The clinical and epidemiological profile of sporadic amyotrophic lateral sclerosis (ALS), a chronic, degenerative, progressive motor neuron disease of unknown etiology, was described and evaluated in the city of Rio de Janeiro.
METHOD:
Patients with a diagnosis definite of ALS according to the revised criteria of the El Escorial World Federation of Neurology were included in this retrospective, descriptive study (n=227). Demographic data, clinical variables, mortality and survival of these patients were assessed.
RESULTS:
Of the 227 included cases, 143 (63%) were male and 84 (37%) were female, resulting in a male/female ratio of 1.7:1. Mean age at onset of the disease was 53.6±12.1years, overall median survival time was 49months (95%CI: 42.4-55.5) and the majority of patients (71.4%) were white, black patients 15.9% and mulattos 12.8%. The most common forms of the disease were classic and bulbar ALS.
CONCLUSION:
Taking classic and bulbar ALS together, the disease was more common in white, male patients of 50 to 70 years of age. When analyzed separately, the bulbar form was more common in women and in older patients. Survival of patients with bulbar ALS was shorter compared to that of patients with classic ALS.

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per·se·vere [pur-suh-veer] - to persist in anything undertaken; maintain a purpose in spite of difficulty, obstacles, or discouragement; continue steadfastly.

Hello Perse

Good to see you in action. The old hybrid certainly puts up a good fight against the Devil's dangly bits.

I'm mushroom white so I suppose it was my destiny to be shafted by Beelzebub.

( BTW, I have some faith in that stuff brewed up by the Japanese gentleman for MS. It will go down very well with my yakisoba ).

D.

http://www.youtube.com/watch?v=-ePRAMojFRM

Mary's posting on mixed ancestry as suggested by the presence of G6PD type A phenotype in the cells and Positive or negative? High blood sugar levels decrease G6PD activity.

Should the positive results with NP001 be due to the fact that it inhibits G6PD, then monitoring the enzyme in SALS family members may be warranted. Perhaps they could then be placed on a preventative dose.

................................................................
Looking at G6PD and what it does...including G6PD deficiency


Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme in the pentose phosphate pathway (see image, also known as the HMP shunt pathway). G6PD converts glucose-6-phosphate into 6-phosphoglucono-δ-lactone and is the rate-limiting enzyme of this metabolic pathway that supplies reducing energy to cells by maintaining the level of the co-enzyme nicotinamide adenine dinucleotide phosphate (NADPH). The NADPH in turn maintains the supply of reduced glutathione in the cells that is used to mop up free radicals that cause oxidative damage.

The G6PD / NADPH pathway is the only source of reduced glutathione in red blood cells (erythrocytes). The role of red cells as oxygen carriers puts them at substantial risk of damage from oxidizing free radicals except for the protective effect of G6PD/NADPH/glutathione.

People with G6PD deficiency are therefore at risk of hemolytic anemia in states of oxidative stress. Oxidative stress can result from infection and from chemical exposure to medication and certain foods. Broad beans, e.g., fava beans, contain high levels of vicine, divicine, convicine and isouramil, all of which are oxidants.

When all remaining reduced glutathione is consumed, enzymes and other proteins (including hemoglobin) are subsequently damaged by the oxidants, leading to electrolyte imbalance, cross-bonding and protein deposition in the red cell membranes

Although female carriers can have a mild form of G6PD deficiency (dependent on the degree of inactivation of the unaffected X chromosome—see lyonization), homozygous females have been described; in these females there is co-incidence of a rare immune disorder termed chronic granulomatous disease (CGD).

G6PDH is the most common human enzyme defect, being present in more than 400 million people worldwide
................................................................

G6PD deficiency is tied to glutathione consumption

It is an antioxidant, preventing damage to important cellular components caused by reactive oxygen species such as free radicals and peroxides.[2]

Glutathione is not an essential nutrient (meaning it does not have to be obtained via food), since it can be synthesized in the body from the amino acids L-cysteine, L-glutamic acid, and glycine.

Glutathione has multiple functions:
It is the major endogenous antioxidant produced by the cells, participating directly in the neutralization of free radicals and reactive oxygen compounds, as well as maintaining exogenous antioxidants such as vitamins C and E in their reduced (active) forms.[17]

Regulation of the nitric oxide cycle, which is critical for life but can be problematic if unregulated[18]

It is used in metabolic and biochemical reactions such as DNA synthesis and repair, protein synthesis, prostaglandin synthesis, amino acid transport, and enzyme activation. Thus, every system in the body can be affected by the state of the glutathione system, especially the immune system, the nervous system, the gastrointestinal system and the lungs.[4]

It has a vital function in iron metabolism. Yeast cells depleted of or containing toxic levels of GSH show an intense iron starvation-like response and impairment of the activity of extra-mitochondrial ISC enzymes, followed by death.[19
...............................

Notice the reference to iron starvation has that has also been implacated in some ALS results
..............................................
Glutathione has recently been used as an inhibitor of melanin in the cosmetics industry. In countries like Japan and the Philippines, this product is sold as a whitening soap. Glutathione competitively inhibits melanin synthesis in the reaction of tyrosinase and L-DOPA by interrupting L-DOPA's ability to bind to tyrosinase during melanin synthesis
...................................................
In the above it has a fuction on malanin and I think my vitiligo started at the same time my sysmptoms did
......................................................................
Raising GSH levels through direct supplementation of glutathione is difficult. Research suggests that glutathione taken orally is not well absorbed across the gastrointestinal tract.

In a study of acute oral administration of a very large dose (3 grams) of oral glutathione, Witschi and coworkers found "it is not possible to increase circulating glutathione to a clinically beneficial extent by the oral administration of a single dose of 3 g of glutathione."[25][26]

Calcitriol, the active metabolite of vitamin D synthesized in the kidney, increases glutathione levels in the brain and appears to be a catalyst for glutathione production.[27]
........................................................

In the above vitamin D has a role to play !

........................................................

In addition, plasma and liver GSH concentrations can be raised by administration of certain supplements that serve as GSH precursors. N-acetylcysteine, commonly referred to as NAC, is the most bioavailable precursor of glutathione.[28] Other supplements, including S-adenosylmethionine (SAMe)[29][30][31] and whey protein[32][33][34][35][36][37] have also been shown to increase glutathione content within the cell.

NAC is available both as a drug and as a generic supplement. Alpha lipoic acid has also been shown to restore intracellular glutathione.[38][39] Melatonin has been shown to stimulate a related enzyme, glutathione peroxidase,[40] and silymarin, an extract of the seeds of the milk thistle plant (Silybum marianum), has also demonstrated an ability to replenish glutathione levels in lab rats.[41][42]

...................................................

All of the above supplements have been recommended at one time or another for PALS

....................................................

Low glutathione is also strongly implicated in wasting and negative nitrogen balance,[48] as seen in cancer, AIDS, sepsis, trauma, burns and even athletic overtraining. Glutathione supplementation can oppose this process, and in AIDS, for example, result in improved survival rates.[49]


All the above info has been taken from Wikipedia, the free encyclopedia

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Into the heart, an air that kills, from yon far country blows.
What are those blue remembered hills, what sphires what farms are those.
That is the land of lost content,I see it shining plain,
The happy highways where I went and cannot come again