http://www.vnews.com/06092009/5737158.htm

Disease Cluster Found at Lake
Researchers Seek Link Between Mascoma ALS, Algae
By John P. Gregg and John Woodrow Cox
Valley News Staff Writer

Enfield -- Researchers with Dartmouth-Hitch*****Medical Center have identified a potentially significant cluster of Lou Gehrig's disease cases around Mascoma Lake.

Working with a team of other researchers, they are trying to determine if the cluster, and smaller ones like it in New Hampshire, Vermont and Maine, can be linked to certain algae blooms that produce a neurotoxin that may trigger the disease.

They also noted that the link, if one can be found, would likely involve long-term exposure to the neurotoxin by people with a genetic predisposition to the disease, officially known as amyotrophic lateral sclerosis, or ALS.

Nine people living near Mascoma Lake have been diagnosed with ALS since 1990, all but one between 2000 and 2006. Three of them were in 2006, according to Elijah Stommel, a DHMC neurologist who has been mapping cases of the disease in New Hampshire, Vermont and Maine.

“There's clearly a cluster of ALS around that lake,” Stommel said in a phone interview yesterday. “I want to be really clear that we don't have any strong link at this point … I don't think there’s any cause for alarm.”

ALS is a progressive, often fatal neurodegenerative disease that attacks nerve cells in the brain and spinal cord, leading to muscle weakness and atrophy, according to the ALS Association.

The incidence of ALS in the United States is about two per 100,000 people. The Dartmouth team has determined that the incidence of ALS cases can double for people living near waterways with cyanobacteria blooms.

The Mascoma Lake prevalence is about 25 times greater than national norms, he said.

Three cases of ALS also were mapped near Kennedy Pond in Windsor, Stommel said.

“We've found a few hotspots in Vermont as well,” he said.

Stommel -- collaborating with researchers from University of New Hampshire, the Wyoming-based Institute for Ethnomedicine and the New Hampshire Department of Environmental Services -- hopes to determine whether the ALS cases near Mascoma and other smaller clusters are related to outbreaks of cyanobacteria.

Cyanobacteria are photosynthetic, single-celled organisms that commonly occur in New Hampshire and Vermont lakes and ponds. But the bacteria can colonize in nutrient-rich or warm waterways, forming a blue-green scum on the water surface, according to the DES Web site.

The suspected ALS trigger is the neurotoxic amino acid Bmaa (B-Methylamino-L-alanine), which can be produced by cyanobacteria and has been found in the brain samples of ALS patients, and other people with neurodegenerative diseases, in recent studies.

The researchers are applying for a federal grant from the National Institute of Environmental Health Sciences to analyze water, hair and other samples from clusters in northern New England that could prove the suspected link.

“At this point we are really just beginning the research. We are really interested in Dr. Stommel's findings. We think they are very important,” said Paul Cox, the executive director of the ethnomedicine research institute in Jackson Hole, Wyo.

Cox, who has conducted groundbreaking work on Bmaa, said “a small percentage of the population” might be vulnerable to the neurotoxin, but that most others may be able to metabolize or excrete it.

“The hypothesis is that in those people it can trigger neurodegenerative diseases, including ALS,” Cox said. “Most people probably would not be affected by it at low concentrations.”

Stommel also emphasized that there is no need for public alarm.

“I don't think that people overall should be terribly panicked, because you probably need a genetic predisposition,” he said.

The Dartmouth and DES teams have saved water and other samples from the areas of concern and are collecting more, to determine if Bmaa was present.

Stommel said brain and spinal cord tissue samples from some of the ALS patients who died would also be analyzed for the study.

Jody Connor, the limnology center director for DES, said researchers also might analyze hair samples from dogs and humans that have been in waters infected with cyanobacteria.

“There are still a number of things we are trying to work through. Anything we think can show some links, we'll be looking at that,” he said.

Connor and others also noted that Mascoma Lake is far cleaner than it was in the 1960s and 1970s, when the state had to treat it regularly for sewage.

“Since that time the lake has cleared up significantly,” he said.

News of the possible link, first reported in the New Hampshire Sunday News, prompted concern from officials in Enfield.

Phil Neily, the building and health inspector in Enfield, said there have been no confirmed cyanobacteria blooms on the lake this year, but that historically some residents with camps along the lake tapped it for domestic water uses.

“I know there were lines directly into the lake,” Neily said. “I'd like to see the research and I need to know more about it.”

Cyanobacteria exposure is believed to potentially occur through a variety of means, including drinking, showering, swimming, boating or eating fish from infected waters.

Enfield Town Manager Steve Schneider also said he wanted to learn more.

“It's alarming, I guess, if it turns out to be true,” Schneider said. “…It may have been a result of the health of the lake 20 or 30 years ago. Who knows?”

Meanwhile, cyanobacteria outbreaks continue to occur in the region.

Connor, the DES lakes-quality expert, said Goose Pond in Canaan was posted Friday with a cyanobacteria warning after the bacteria was found there. A similar warning was issued for Harvey Lake in Northwood, N.H., yesterday.

Residents are advised not to swim, drink or wade in the water if they see any blue-green scum, and all pets should be kept out of the water until the warnings are lifted.

John P. Gregg can be reached at jgregg@vnews.com or (603) 727-3213.

So this connects with Kurland's cycad palm Guamian ALS theory, which has been tweaked as well as critiqued since he proposed it (see below; note one author is Oliver Sacks, a thinker out of the box if ever there was one). β-Methylamino-L-alanine, or BMAA, is a neurotoxin found in the seeds of the cycad. This non-proteinogenic amino acid (very similar to the non-essential amino acid alanine) is produced by cyanobacteria of the genus Nostoc that live on the plant's roots. Kurland suggested that exposure to plant neurotoxins from the cycad palm was the cause of Guamian ALS.

So one wonders, which came first in terms of the Vermont cluster. The theory or the evidence. Did they look for the theory and there it was?

Cycad neurotoxins, consumption of flying foxes, and ALS-PDC disease in Guam
Paul Alan Cox, PhD and Oliver W. Sacks, MD

From the Institute for Ethnobotany (Dr. Cox), National Tropical Botanical Garden, Kalaheo, HI; and Department of Neurology (Dr. Sacks), Albert Einstein College of Medicine, Bronx, NY.

The Chamorro people of Guam have been afflicted with a complex of neurodegenerative diseases (now known as ALS-PDC) with similarities to ALS, AD, and PD at a far higher rate than other populations throughout the world. Chamorro consumption of flying foxes may have generated sufficiently high cumulative doses of plant neurotoxins to result in ALS-PDC neuropathologies, since the flying foxes forage on neurotoxic cycad seeds

The ALS/PDC syndrome of Guam and the cycad hypothesis.
Neurology. 2008 May 20;70(21):1984-90.
Steele JC, McGeer PL.
Guam Memorial Hospital, Agana.

There is a high incidence on Guam of a severe tauopathy known as the Parkinson- dementia complex (PDC). It is linked with an even more malignant amyotrophic lateral sclerosis (ALS) syndrome. There is great interest in determining the cause, or causes, of the Guam ALS/PDC syndrome because insight might be gained regarding ALS and the more common tauopathies found throughout the world. Research into the disorder is stimulated by hypotheses as to cause. Such hypotheses should be compatible with the known epidemiology and pathology of the syndrome. These include a high, if not exclusive, restriction to the Chamorro population, familial occurrence, a regional variation on Guam itself, a definite persistence but with declining incidence, and a possible duplication in isolated villages on the Kii peninsula of Japan. Proposed causation factors should also be able to reproduce the syndrome in experimental systems. This includes induction of neurofibrillary tangles with a tau isoform distribution similar to that of Alzheimer disease and association of the lesions with TDP-43 and Lrrk2. A recurring hypothesis as to causation is exposure to Cycas micronesica, the false Sago palm known locally as fadang. We review the reasons why this hypothesis falls short of the minimal criteria needed for further serious consideration and discuss some other possibilities that should not be excluded.

Thanks for posting this. I think it is a very important.
There has been discussion about BMAA in other threads
The universe within http://www.als.net/forum/Default.aspx?g=posts&t=44338
ALS TDI mouse study publication http://www.als.net/forum/Default.aspx?g=posts&t=45710&p=2
One article noted there can be a very long lag time between exposure to the toxic and disease development (e.g., 30 years)

The article ENV mentioned in the last post found:
So all lakes might pose some danger. How does it pose the danger? drinking its water? swimming? eating fish? breathing the air?

I wonder if there are any epidemiological studies on the incidence of ALS and water supply sources. If this theory is correct, I would think people who get their water from an aquifer would have a lower incidence.


Mike

Some of the earlier postings are off topic and should be in another thread. Please contain yourself.

More on the cluster from the MDA
Mike

http://www.mda.org/publications/Quest/extra/jun09/pond_scum.html
excerpts:
ALS 'Lake Link' Tenuous
Does pond scum cause ALS? Maybe – but the evidence is far from clear.

Recent media reports have raised the question of a possible link between an increased risk of developing amyotrophic lateral sclerosis (ALS) and living near Lake Mascoma in Western New Hampshire.
She noted during her presentation that there is no scientific proof of a correlation between cyanobacteria toxin in lake water and ALS.

Lorene Nelson, an epidemiologist at Stanford (Calif.) University who has MDA funding to study genetic and environmental interactions in ALS, noted that many reported "clusters" of ALS "have not withstood scientific scrutiny." She said a certain number of apparent ALS clusters can be expected to occur on the basis of chance alone. Others occur not because of anything in the environment but because of factors such as a skewed age distribution, as ALS is a disease that strikes mainly older people.

She noted that the town of Enfield, in which the lake is partly located, has six housing projects for elderly residents, while most other towns in New Hampshire have one or two.

Nelson said cyanobacteria are extremely common in soil, as well as in sea water and fresh water, and are believed to cause damage to the liver after acute exposure. "The possible long-term effects on the risk of later-life cancer or neurological diseases is not known," she said.

Supporting an ALS-cyanobacteria link, she said, is another ALS “cluster” on the Pacific island of Guam. It’s hypothesized that the higher-than-average incidence of ALS on Guam is related to a cyanobacterial toxin called BMAA, which is ingested when people eat bats in which the toxin has accumulated.

It seems to me that these suspected clusters are the perfect opportunity for us to build a fire under the CDC to get the ALS Registry moving.

I'm not a epidemiologist, but my instincts are that having good baseline data is essential to understanding whether there is a cluster or not.

In the meantime, as long as healthy people squirm a little when these stories are published, perhaps we'll get the national resolve to finally start collecting the dots.

My 2 cents fwtw.

Dr. M, thanks so much for being a part of this forum! Agree or not, I know if no other place where people with questions and opinions about ALS research can converse actively with somebody actually engaged in the work.

"her gait returned to normal"

Medical News Article on Neurodegenerative Disease

Research data from G.L. Forni and colleagues update understanding of
neurodegenerative disease


2008 JUN 23 -- "We report the results of iron chelating treatment with
deferiprone in a 61-year-old woman with signs and symptoms of
neurodegeneration with brain iron accumulation (NBIA)," scientists in
Genoa, Italy report.
"After 6 months of therapy the patient's gait had improved and a
reduction in the incidence of choreic dyskinesias was observed," wrote
G.L. Forni and colleagues.


The researchers concluded: "Her gait returned to normal after an
additional 2 months of therapy, at which time there was a further
reduction in involuntary movements and a partial resolution of the
blepharospasm."


Forni and colleagues published their...


In order to view the entire article, please read your options to the
right


Mov Disord. 2008 Apr 30;23(6):904-7. Links
Regression of symptoms after selective iron chelation therapy in a
case of neurodegeneration with brain iron accumulation.Forni GL,
Balocco M, Cremonesi L, Abbruzzese G, Parodi RC, Marchese R.
Centro della Microcitemia e Anemie Congenite, Ospedale Galliera,
Genoa, Italy. gianluca.fo...@galliera.it


We report the results of iron chelating treatment with deferiprone in
a 61-year-old woman with signs and symptoms of neurodegeneration with
brain iron accumulation (NBIA). After 6 months of therapy the
patient's gait had improved and a reduction in the incidence of
choreic dyskinesias was observed. Her gait returned to normal after an
additional 2 months of therapy, at which time there was a further
reduction in involuntary movements and a partial resolution of the
blepharospasm. (c) 2008 Movement Disorder Society.


PMID: 18383118

---

I suppose someone should phone his mom .. ?


"Progressive worsening of walking"


Systemic sclerosis and superficial siderosis of the central nervous
system: casuality or causality?
Rheumatol Int. 2008 Jun;28(8):815-8. Epub 2008 Jan 12
Simeoni S, Puccetti A, Tinazzi E, Tomelleri G, Corrocher R, Lunardi
C.
Department of Clinical and Experimental Medicine, Section of Internal
Medicine, University of Verona, Policlinico GB Rossi, Piazzale LA
Scuro, 37134, Verona, Italy.


We describe the case of a 59 year old man with systemic sclerosis and
superficial siderosis of the central nervous system characterized by
progressive worsening of walking with signs of pyramidal liberation
associated with cerebellar ataxia and bilateral hypoacusia.
Ferritin and oligoclonal bands were found on lumbar puncture and
Magnetic Resonance Imaging of the brain and spinal cord revealed a
rim
of hypointensity in T2-weighted images enveloping the surface of
brain
and spinal cord, typical of hemosiderosis.
Neurological complications, both central and peripheral, are thought
to be rare and coincidental in systemic sclerosis; however over the
past decade, some authors have reported a high incidence (up to 40%)
of neurological involvement in the disease.
In this report we consider the hypothesis that superficial siderosis
may be a direct complication of systemic sclerosis.
To our knowledge, this case represents the first description of
superficial siderosis in a patient with systemic sclerosis.


PMID: 18193230

---

Herbivore Hypothesis
http://sites.google.com/site/herbivorehypothesis/age-related-iron-accumulation

The reports regarding the ALS cluster in New Hampshire do not mention that the statistics were derived from "age adjusted" calculations. Without the original study we are unable to critique the numbers effectively.

In case the "off topic" complaint related to my post, the intent was to demonstrate particular toxins that are known to accumulate around bodies of water, i.e., a lake, that have low exchange rates. Statistics were mentioned regarding an increase of ALS around lakes and the site in NH was around at lake.

The next question might be "Are there more older people living around lakes?" and was the research regarding ALS and lakes "age adjusted"? Would "age adjusted" statistics give us a correct perception of mortality from ALS?

Donna

http://des.nh.gov/organization/divisions/water/wmb/vlap/2006/observations/documents/mascoma_lake_enfield.pdf

"iron and manganese deposits in bedrock"

---

Herbivore Hypothesis
http://sites.google.com/site/herbivorehypothesis/age-related-iron-accumulation

I'm not sure about using walkabouts in Iraq as a viable study population ..
Depleted uranium and lack of water all bring about different symptoms and stress ..

---

Herbivore Hypothesis
http://sites.google.com/site/herbivorehypothesis/age-related-iron-accumulation

Dietary intakes of fat and antioxidant vitamins are predictors of
subclinical inflammation in overweight Swiss children.
Aeberli I, Molinari L, Spinas G, Lehmann R, L'allemand D, Zimmermann MB
Am J Clin Nutr. 2006 Oct ; 84(4): 748-55

BACKGROUND: In obese children, subclinical inflammation is often
present and is correlated with the metabolic syndrome. Dietary factors,
such as fatty acids and antioxidants, potentially modulate the
association between adiposity and subclinical inflammation, but few
data are available in children. OBJECTIVE: The aim of the study was to
determine whether dietary fat or antioxidant intakes influence
circulating tumor necrosis factor alpha (TNF-alpha), interleukin 6
(IL-6), C-reactive protein (CRP), and leptin concentrations in
overweight children. DESIGN: In a cross-sectional study of 6-14-y-old
normal-weight (n = 33), overweight (n = 19), and obese (n = 27) Swiss
children, nutritional intakes were assessed from two 24-h dietary
recalls and a 1-d dietary record. Percentage body fat from skinfold
thicknesses, waist-hip ratio, and blood pressure were measured. Fasting
blood samples were collected for the measurement of insulin, glucose,
HDL-cholesterol, triacylglycerol, CRP, IL-6, TNF-alpha, and leptin
concentrations. RESULTS: CRP, IL-6, and leptin increased significantly
(P < 0.02) with increasing adiposity, independent of age; TNF-alpha did
not increase. Total dietary fat and the percentage of energy from fat
were significant predictors of CRP concentration, independent of body
mass index (P < 0.05). Meat intake was a significant predictor of IL-6
and leptin, independent of body mass index (P < 0.05). Intakes of
antioxidant vitamins (vitamins E and C and beta-carotene) were
significant predictors of leptin (P < 0.05) but not of CRP, IL-6, or
TNF-alpha. CONCLUSIONS: Overweight Swiss children as young as 6 y have
elevated concentrations of inflammatory markers. Intakes of total fat
and antioxidant vitamins are determinants of subclinical inflammation
in this age group.


---------------------------------------------------------------------------­-------------------------------


Molecule May Drive Multiple Sclerosis-Linked Disorder
Discovery could lead to treatments for transverse myelitis and MS


WEDNESDAY, Oct. 12 (HealthDay News) -- Researchers report that a single


molecule called IL-6 is the cause of transverse myelitis (TM), an
autoimmune disease in the central nervous system that's related to
multiple sclerosis.


The study found that levels of IL-6 are dramatically elevated in the
spinal fluid of people with TM. The finding may help in the development


of treatments for both TM and multiple sclerosis.


"This is the first time a single culprit has been identified as causing


a CNS (central nervous system) autoimmune disease," researcher Dr. Adam


Kaplin, a psychiatrist and assistant professor of medicine at Johns
Hopkins University School of Medicine, said in a prepared statement.


IL-6 is a chemical messenger that immune system cells use to
communicate with each other. Most TM patients suffer a single attack,
but 15 percent to 30 percent of TM patients go on to develop full-blown


multiple sclerosis. TM usually results in permanent impairment,
including leg and arm weakness, bowel and bladder dysfunction, pain and


paralysis.


The researchers decided to investigate IL-6 because TM patients suffer
from memory impairment and depression. Previous research implicated
IL-6 in mood and concentration disorders.


The study appears in the October issue of the Journal of Clinical
Investigation.


More information


The U.S. National Institute of Neurological Disorders and Stroke has
more about transverse myelitis.


-- Robert Preidt


SOURCE: Johns Hopkins Medicine, news release, news release, Sept. 22,
2005


Last Updated: Oct. 12, 2005


Copyright © 2005 ScoutNews LLC. All rights reserved


--------------------------------------------------------------


<<snip>>
IL6-induced BBB defect precipitates iron accumulation
<<snip>>


J Neuropathol Exp Neurol. 1998 Mar;57(3):268-82. Related Articles,
Links


Abnormal iron deposition associated with lipid peroxidation in
transgenic mice expressing interleukin-6 in the brain.


Castelnau PA, Garrett RS, Palinski W, Witztum JL, Campbell IL, Powell
HC.


Department of Pathology (Neuropathology), School of Medicine,
University of California San Diego and the Veterans Affairs Research
Service, La Jolla 92093-0612, USA.


Transgenic mice, named GFAP-IL6, that express interleukin-6 in
astrocytes in the central nervous system (CNS) have a constitutive
blood-brain barrier (BBB) defect and develop a progressive
neurodegenerative disease. Based on ultrastructural observations
showing electron-dense pigment in the brain of the GFAP-IL6 mice, we
hypothesized that iron metabolism was altered in the brains of these
animals. Enhanced histochemical methods revealed abnormal iron
deposition in the cerebellum from 1 month of age that worsened with
progression of the disease. Immunohistochemical analysis of
iron-binding proteins (IBP) showed increased ferritin immunoreactivity
and a decreased signal from the transferrin receptor in symptomatic
animals. Atomic absorption spectroscopy revealed a 40% increase of
total iron concentration in the cerebellum at the symptomatic stage. In


order to obtain evidence that accumulation of this oxidizing metal was
toxic, we looked for the presence of oxidative damage. Using the MAL-2
antibody, extensive lipid peroxidation (LP) was detected in the
neocortex and the cerebellum in symptomatic animals. Ultrastructural
analysis indicated lipofuscin deposition at the sites of neuro-axonal
degeneration and abnormal iron deposition. These results suggest that
the IL6-induced BBB defect precipitates iron accumulation in the
GFAP-IL6 mouse brain and that subsequent IBP regulation mediates
protective responses. As these defenses become overwhelmed, the iron
overload seems to promote LP, which may contribute to the
neurodegeneration that ensues. This transgenic mouse model of
IL6-mediated neurodegeneration provides a unique opportunity to examine


several aspects of iron metabolism in the brain, including its entry at


the site of the BBB, its distribution through the IBP, and its
mechanisms of toxicity.


PMID: 9600219 [PubMed - indexed for MEDLINE]


---------------------------------------------------------------------------­­-----


Evidence of involvement of leptin and IL-6 peptides in the action of
interferon-beta in secondary progressive multiple sclerosis.
Angelucci F, Mirabella M, Caggiula M, Frisullo G, Patanella K,
Sancricca C, Nociti V, Tonali PA, Batocchi AP
Peptides. 2005 Nov ; 26(11): 2289-93


Leptin is a peptide hormone which acts on cells of immune system by
influencing the production of cytokines. Serum leptin levels and
cytokine production by peripheral blood mononuclear cells (PBMC) were
measured in 18 secondary progressive multiple sclerosis (SPMS) patients
under IFN-beta-1b treatment. There were no overall effects on leptin,
interleukin-6 (IL-6), IL-10 and IL-12 p40 after 2, 6 and 12 months of
treatment. However, leptin and IL-6 decreased after 6 and 12 months of
treatment in 12 patients who did not show progression of disability.
Thus, our pilot data show that the beneficial effect of IFN-beta on
some SPMS patients might be associated with the reduced levels of
leptin and reduced IL-6 production by PBMC.

---

Herbivore Hypothesis
http://sites.google.com/site/herbivorehypothesis/age-related-iron-accumulation