*Switch off, switch on* -B-cell Depletion Therapy

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>>>> 5 July 2009 <<<<

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TheNational

 

Switch off, switch on

_http://www.thenational.ae/article/20090705/OPINION/707049916/1036_

(http://www.thenational.ae/article/20090705/OPINION/707049916/1036)

Robert Matthews

Last Updated: July 04. 2009

_http://bit.ly/17Jk9m_ (http://bit.ly/17Jk9m)

 

Switch off, switch on

 

 

We’ve all done it. Faced with some malfunctioning gadget or computer, we

pull the plug on it, switch it back on – and find it works perfectly again.

Known to the cognoscenti as the “hard rebootâ€, it’s a trick used more

often in desperation than insight. Now it’s emerging as a promising new

approach

to treating some notoriously debilitating medical conditions.

 

 

Recent clinical trials have shown that “rebooting†our disease-fighting

immune system can dramatically improve the condition of patients with

multiple sclerosis and rheumatoid arthritis. Two British scientists are treating

rheumatoid arthritis and multiple sclerosis by destroying patients' B-cells

and starting over with fresh ones. Visuals Unlimited/ Corbis. And according

to a study published last week, it may even bring relief to patients

suffering from the enigmatic condition Chronic Fatigue Syndrome, affecting

millions worldwide.

 

 

There is a growing sense of excitement about the rebooting technique. But

behind it lies an inspiring story of how a pair of scientists overcame

indifference to convince the medical community of the merits of what is now

called B-cell Depletion Therapy (BCDT).

 

 

B-cells are a type of white blood cell which randomly churn out so-called

antibodies, many of which prove useful in destroying disease-causing

pathogens. Yet, like every defence system, mistakes sometimes happen – and

innocent bystanders end up being targeted.

During the late 1990s, two medical researchers at University College

London began to wonder if this “friendly fire†might hold the key to the

debilitating disease rheumatoid arthritis (RA).

 

 

Affecting about one in 100 people worldwide, RA can strike anyone

literally overnight, their immune system suddenly attacking their joints. The

condition is excruciatingly painful, and for years there seemed no hope of a

cure. Until recently, the prime culprit was held to be T-cells: white blood

cells that play a key role in the disease-fighting immune system. Yet despite

intensive study, no one could explain how or why T-cells should produce a

lifelong ailment such as RA. Most tellingly of all, therapies targeting

T-cells failed to benefit patients.

 

 

This prompted Professor Jonathan Edwards and Dr Geraldine Cambridge at UCL

to ponder the possibility than B-cells might be to blame. Their idea was

based on the fact some B-cells are known to make antibodies which

inadvertently seek out and destroy healthy tissue. Normally, these would be

destroyed

by the B-cells themselves. But what if some of the antibodies by chance

possessed the means to evade their own destruction – and go on to attack the

joints?

 

 

That led Prof Edwards and Dr Cambridge to a radical new approach to

treating RA: “rebooting†the immune system by destroying all the B-cells,

and

then starting over with fresh ones.

 

 

Fortunately, a compound capable of targeting just B-cells had just become

available: rituximab, a so-called monoclonal antibody which homes in on

specific targets like a heat-seeking missile. This could destroy all the

B-cells, leaving patients to develop a whole new set free of the renegade

variety

that attack joints. That at least was the theory, and with the standard

T-cell theory not getting anywhere, the team thought it was worth bringing to

the attention of other researchers. They soon found that new ideas aren’t

always welcome in science – even if the old ones aren’t working.

 

 

Their academic papers were rejected by journals as “obviously†wrong – on

the grounds that they focused on B-cells, not T-cells.

 

 

They were not helped by a lack of experimental evidence. Yet the pair

found themselves in a chicken-and-egg scenario: only if they already had

evidence from clinical trials could they persuade funding bodies to pay for

more

clinical trials.

 

 

The pair managed to publish their idea in a medical journal, only to be

met with silence. Determined to make their case, they set up a small but

demanding test, using rituximab to treat five patients with severe RA. The

results were impressive: once their B-cell systems had been “rebootedâ€,

their

condition improved dramatically. Yet attempts to publish the results in

journals were rebuffed on the grounds that the study involved too few

patients.

 

 

So the pair tried again, cobbling together enough money to treat 20

patients. Again, the results were impressive, with all but two of the patients

showing dramatic improvements. It made no difference: the medical community

remained utterly unimpressed.

 

 

Frustrated by the lack of interest, Prof Edwards and Dr Cambridge decided

some media coverage might help. When the reports of their success with 20

patients emerged, they found themselves vilified by fellow academics as

hype-mongers.

 

 

Whatever the rights or wrongs of their decision to approach the media, it

certainly boosted awareness of the B-cell depletion theory.

 

In 2000, just six people had turned up to hear a lecture about the theory;

a few months later, the media coverage led to 3,000 packing a lecture hall

to hear what it was all about.

 

 

The coverage also helped win funding for a substantial clinical trial

involving more than 160 patients.

 

By 2002, the results were in: when combined with a standard therapy for

RA, rituximab proved three times more effective than the standard therapy

alone.

 

In 2006, the B-cell depletion therapy (BCDT) was approved by regulators in

the US and Europe for use alongside the standard therapy.

 

 

Despite this vindication, the two researchers have not rested on their

laurels. Since the late 1990s, they have suggested that BCDT might help in

treating another disease linked to a malfunctioning immune system: multiple

sclerosis.

 

 

Last year, a study of more than 100 patients showed that BCDT could halve

their relapse risk. The UCL team has also shown that the technique brings

benefits to patients with the auto-immune disease, lupus.

 

 

Now a team of researchers in Norway is claiming the therapy could help

treat Chronic Fatigue Syndrome, sometimes called myalgic encephalomyelitis

(ME). Characterised by mental and physical exhaustion, with muscle and joint

pain, this enigmatic condition has no accepted cause.

 

Many researchers have suspected a link with the immune system – a

possibility now tentatively backed by researchers at Haukeland University

Hospital,

Norway. In the current issue of the online journal BioMed Central-

Neurology, the team reports treating three CFS patients with BCDT, and observing

marked improvements.

 

With so few patients, it’s hardly definitive proof of a cure. Yet it is

just the situation Prof Edwards and Dr Cambridge found themselves in a decade

ago. CFS sufferers must be hoping medical researchers are not about to

repeat history by rejecting these intriguing findings out of hand – despite

not

having any better ideas themselves.

 

 

 

 

Robert Matthews is a Visiting Reader in Science at Aston University,

Birmingham, England

 

 

 

````````

 

Rituximab

 

From Wikipedia, the free encyclopedia

 

Rituximab, sold under the trade names Rituxan and MabThera, is a chimeric

monoclonal antibody against the protein CD20, which is primarily found on

the surface of B cells. Rituximab is used in the treatment of many

lymphomas, leukemias, and some autoimmune disorders. See: _http://bit.ly/ZkUa9_

(http://bit.ly/ZkUa9)

 

 

``

 

See also next Help ME Circle:

*Clinical impact of B-cell depletion with the anti-CD20 antibody rituximab

in CFS*

 

 

~jvr

 

 

 

 

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