Saturday, June 6, 2009

ME: Proof that it isn't all in the mind?


Belgian doctors, Professor Kenny De Meirleir and Dr Chris Roelant, have developed a simple test that, they claim, solves the mystery of 'yuppie flu'.

By Liz Hunt, Published: 7:00AM BST 01 Jun 2009

Anna's deterioration was rapid and unrelenting. One moment the pretty, young Scandinavian woman was at the peak of youthful vitality, newly married and excited about the future. The next, that future was much diminished, her life limited to the environs of her bedroom, and dictated to by the illness that had overwhelmed her.


It had started with persistent fatigue, muscle pain, and a growing sensitivity to light after a honeymoon trip to Mexico in the summer of 2006. By December, she was in a wheelchair. Three months later she was bedridden, her face pale, her features shrunken, barely able to move or talk, and being fed through a naso-gastric tube.

Anna – not her real name as her identity is being protected at the request of her family – was the subject of a short film shown at a conference in London last week. Her case, according to Professor Kenny De Meirleir of the Vrije Universiteit Brussel, Belgium, illustrates the worst ravages of myalgic encephalomyelitis/encephalopathy or ME, also known as chronic fatigue syndrome or post viral fatigue syndrome.

Once it was derided as "yuppie flu" because, following its emergence in the early Eighties, its "typical" victim was, supposedly, a high-achieving young professional. ME was also assumed by many doctors, and much of the public, to be psychosomatic in origin – if it existed at all.

In more enlightened times, ME is now accepted by the World Health Organisation, and Britain's medical royal colleges, as a complex, chronic disease of varying severity characterised by a complex set of symptoms. (In addition to extreme fatigue, and general malaise, there are musco-skeletal symptoms, especially muscle pain, brain and central nervous symptoms, evidence of immune system dysfunction, mood swings, depression etc.) According to the ME Association, there are 250,000 sufferers in Britain.

The debate about the cause of ME continues to flourish at conferences, in journals and on websites: are the symptoms a physical manifestation of a problem in the brain such as a chemical imbalance; is sustained stress or exertion to blame; or is ME the result of abnormal physiological functioning, with an organic cause, such as a viral or bacterial infection, or exposure to a toxic agent?

The answer is crucial because it determines the direction of research funding which has, according to Prof De Meirleir, for too long been skewed in favour of a psychiatric approach. He hopes to change that. After more than 20 years of investigation, and having assessed and treated thousands of patients in Europe and America, Prof De Meirleir, who is an internist at the Himmunitas Foundation in Brussels (a non-profit organisation specialising in chronic immune disorders), believes he has identified a mechanism to explain the development of ME that opens up new treatment options.

In addition, he and his fellow Belgian, Dr Chris Roelant, Chief Operating Officer of the diagnostics company Protea biopharma, have developed a self-diagnosing urine test for ME. If they are correct – and that must be determined by scrutiny of their research and use of the test by other scientists and doctors – then it marks an encouraging breakthrough.

The symptoms of ME are wide-ranging and occur in a number of other conditions, so a diagnosis of ME is currently reached only after eliminating other causes.

"This test will tell patients that it is not a problem between their ears, but a real physiological problem," insists Dr Roelant.Prof De Meirleir and Dr Roelant have, somewhat controversially, opted to go public with their findings before publication in a peer-reviewed journal.

They say this is because of the implications of their research, especially for severely debilitated ME patients. At the Invest in ME conference in London last Friday they also raised the possibility of "transmissability" of the illness in this group of patients – another controversial claim.

Prof De Meirleir has never believed that ME is an "illness of the mind". Exercise physiology was his initial area of expertise and it was in this capacity that he was asked by a psychiatrist to assess some of his patients who were suffering from a mystery illness characterised by extreme fatigue.

"One of them was a banker who started work at 9am and had to finish at 11am because he was so exhausted," says Prof De Meirleir. "He did not appear to be suffering from any psychiatric disorder."

The case ignited the young doctor's interest. During a six-month sabbatical at the University of Pennsylvania in 1990, he heard about the "Lake Tahoe epidemic". In 1984, hundreds of people living in a small town on Lake Tahoe in California succumbed to a flu-like illness. The symptoms, including fatigue, neurological and immunological symptoms, persisted in just under 10 per cent of the population (about 300). This was followed by numerous reports of outbreaks of a similar illness around the world, and persuaded Prof De Meirleir of the likelihood of a causative agent being involved in ME, a fact that has heavily influenced his research interests. Since the early 1990s, he has built up a large clinical practice in Brussels where he sees around 2,000 new patients a year. Antibiotics are a cornerstone of his therapeutic approach, as dictated by his research.

In recent years, and in collaboration with a microbiologist, Dr Henry Butt, and his team at the University of Melbourne, Prof De Meirleir has focused on bacteria in the gastro-intestinal tract. "This is an obvious place to start since 80 per cent of immune system cells are located here," he says. A healthy, functioning gut is colonised by "good" bacteria that aid digestion and contribute to our wellbeing. Many ME patients suffer from multiple intestinal symptoms, and Prof De Meirleir believes that an overgrowth of "bad" bacteria, including enterococci, streptococci and prevotella, is to blame. These bacteria are normally present in very small quantities in a healthy gut, but can initiate a sequence of events leading to the multifarious symptoms of ME if they proliferate. (This research will be published in the journal In Vivo, in July).

These "bad" bacteria produce hydrogen sulphide (H2S)– a gas naturally occurring in the body, where it has several functions – in minute quantities. However, in larger quantities, it is a poisonous gas that suppresses the immune system, and damages the nervous system, according to Prof De Meirleir. (Hydrogen sulphide is produced by some animals in preparation for hibernation because it "shuts down" the body which, in effect, is what occurs in ME.) In addition, Prof De Meirleir described how he believes the gas reacts with metals, including mercury, introduced in minute amounts as contaminants in food. The form of mercury produced after reacting with hydrogen sulphide also disrupts the normal production of energy (known as the Krebs Cycle) by individual cells, and this, he says, would explain the energy shortfall experienced by ME patients.

Normal cellular functioning is inhibited and, over time, this generates damaging free radicals, highly reactive molecules that distort the structure of key proteins, such as enzymes and hormones, necessary for chemical reactions. This results in what Prof De Meirleir calls "aberrant" proteins (or prions), which lead to further symptoms as the body is increasingly compromised, and which he says may play a role in the transmissibility of ME.

The urine test, developed by Prof De Meirleir and Dr Roelant in their privately funded research, detects the presence of hydrogen sulphite metabolites, which they say confirm the presence of abnormal quantities of hydrogen sulphide-producing bacteria. The intensity of the colour change in the urine indicates the severity of the disease progression.

Not every ME patient progresses to its most severe form, says Prof De Meirleir, but the varying symptoms can all be explained by this proposed mechanism for the disease. In the worst cases of ME, he says it can be shown that there is an almost complete eradication of "good" bacteria (such as E. coli), the presence of a high number of "bad" bacteria in stools, metal deposits in tissues, and the presence of aberrant proteins in saliva. "What we have shown is that these patients have an organic disease involving one of the most toxic substances [H2S] that exist," he says.

So what causes the proliferation of harmful bacteria in the first place? There are, he says, many potential triggers ranging from food- borne bacterial (eg salmonella) infections, viruses, and toxins, or mental stress. He says many ME sufferers have a history of gut disorders including gluten and lactose intolerance, which may predispose them to colonisation by enterococci and streptococci.

Anna, the 28-year-old Scandinavian patient, is typical in this respect, he claims; she had gut problems in the past, including possible food poisoning while in Mexico. Her treatment focuses on short courses of antibiotics to decrease the numbers of bad bacteria, treatment with probiotic supplements to help restore the good bacteria, plus vitamin and mineral supplements. "She is improving," says Prof De Meirleir.

ME support groups and the medical profession are now considering Prof De Meirleir's work. However, Sir Peter Spencer, chief executive of Action for ME, welcomed the findings, albeit with a caveat: "It is always heartening to see new developments that might bring hope to the 250,000 people in the UK affected by this horrible illness.

"We look forward to seeing Professor Meirleir's findings published in a peer-reviewed journal so that we can develop a better understanding of this research."

Prof De Meirleir says that helping patients like Anna, of whom he has known many, is what has brought him to this point. "This has preoccupied me for more than 20 years. I told [the psychiatrists] we would find a cause, and I believe we have." There are many ME patients and their families who must hope that he is right.

• For more information on the ME urine test see www.proteabiopharma.com

By Liz Hunt, Published: 7:00AM BST 01 Jun 2009

2 comments:

Anonymous said...

Any idea which antibiotics he uses? A proportion of people diagnosed with ME may have other undiagnosed ailments. Lyme Disease also often occurs in outbreaks (well known in America in particular) and is alleviated by antibiotics- has this option been explored as well?

Neelu

Anonymous said...

FASEB J. 2007 Jun;21(8):1699-706. Epub 2007 Feb
21..

Sulfide, the first inorganic substrate for
human cells.

Goubern M, Andriamihaja M, Nübel T, Blachier F,
Bouillaud F.
Ecole Pratique des Hautes Etudes and Nurélice
UR909, INRA, F-78352 Jouy en Josas, France.


Hydrogen sulfide (H2S) is produced inside the
intestine and is known as a poison that inhibits
cellular respiration at the level of cytochrome
oxidase.

However, sulfide is used as an energetic substrate
by many photo- and chemoautotrophic bacteria and
by animals such as the lugworm Arenicola marina.

The concentrations of sulfide present in their
habitats are comparable with those present in the
human colon.

Using permeabilized colonic cells to which sulfide
was added by an infusion pump we show that the
maximal respiratory rate of colonocyte mitochondria
in presence of sulfide compares with that obtained
with succinate or L-alpha-glycerophosphate.
This oxidation is accompanied by mitochondrial
energization.

In contrast, other cell types not naturally exposed to
high concentration of sulfide showed much lower
oxidation rates.

Mitochondria showed a very high affinity for sulfide
that permits its use as an energetic substrate at low
micromolar concentrations, hence, below the toxic
level.

However, if the supply of sulfide exceeds the
oxidation rate, poisoning renders mitochondria
inefficient and our data suggest that an anaerobic
mechanism involving partial reversion of Krebs
cycle already known in invertebrates takes place.


In conclusion, this work provides additional and
compelling evidence that sulfide is not only a toxic
compound. According to our study, sulfide appears to
be the first inorganic substrate for mammalian cells
characterized thus far.


PMID: 17314140 [PubMed - indexed for MEDLINE]

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