Article on future CURE for BPI and it's creator!

[Christopher]

This is a bio article of Professor Geoffery Raisman and his work. Found on the TBPI UK site.

He may be the very man to produce a cure for BPI. The first clinical trials are set to start this fall in London using his work on neural regeneration with Olfactory Ensheathing Glial Cells (stem cell like neural cells taken from the injured patients own nose).

The read may seems long, but very much worth the effort. Hell it's your life he's trying to fix, give it a read thru!

http://www.timesonline.co.uk/article/0, ... 40,00.html


The Sunday Times Magazine

The Sunday Times
April 09, 2006

The miracle worker

He’s obstinate, instinctive, anti-establishment and obsessional. Precisely the qualities that have led many to believe that Geoff Raisman — a tailor’s son from Leeds — holds the key to curing nature’s cruellest afflictions. And so far, he says, ‘the results are beyond our wildest dreams’.

Report by John Cornwell

The Oxford and Cambridge Club, Pall Mall, London. I’m sniffing the potted shrimp while my lunch guest – a rich glint of enthusiasm in his eye – expands on the sexual equipment of a moth. “Your male gypsy moth,” he declares, “has smell sensors that can pick up the odour of an available female 12 miles distant. Your dog smells a bitch on heat from half a mile.” He is Professor Geoff Raisman FRS, a world-class British neuroscientist who has just announced an imminent cure for spinal-cord injury.

He noses his lobster bisque. “Our smelling sensors,” he says, “die and rise again every 60 days. We’re going to use the cells that make pathways for the nerve fibres of those neurons to make the lame walk.”

After a pause, he asserts with biblical resonance: “One day we’ll use them to make the blind see, the deaf hear and the dumb talk!”

This is the story of a scientist who has uncovered the deepest secrets of paralysis after injury, not through wishful thinking and guesswork, but through unflinching focus over 40 years on one of nature’s strangest quirks.

The mechanics of spinal-cord injury have been known for decades, and Raisman has been intimately involved in their discovery. While still in his twenties, he staked a niche in the history of neuroscience by showing that the brain and central nervous system have an astonishing capacity to reorganise themselves after loss or trauma. He called it “plasticity”.

Born and raised in a poverty-stricken district of Leeds, obdurate in his decision to marry the girl of his dreams at 18, thus risking his university education before it even got started, Raisman has always been, by his own admission, “bloody-minded”. As a young researcher he was dubbed a scientific heretic for insisting that a damaged brain and spinal cord can repair themselves; but he has proved his critics wrong. He has always followed his instincts, backed by long-term systematic experiment. He is now about to put to the test in human patients his theory that plasticity can be manipulated to cure some of nature’s cruellest afflictions.

Stem cells, primitive “mother cells”, which in theory can transform into many kinds of tissue or many blood types, are heralding a new era of medical science, with vaunted cures for everything from diabetes to Alzheimer’s. They are also the stuff of scientific flatulence and soiled nests: 2005 will go down in biotech history as the year when an eminent South Korean professor, Hwang Woo-suk (personal salary, $3m per annum), was found to have fabricated results in two papers published in America’s top research journal, Science. Hwang’s papers involved the cloning of embryonic stem cells for therapeutic purposes. His published pictures of cloned human stem cells were fakes. Worse: Nature magazine reports that many stem-cell lines in the laboratories of the world are duds because of a confusion between tagging a cell and correctly identifying its properties. The principle is simple: you can wear a tutu but it doesn’t make you a ballerina.

Yet if Raisman has anything to do with it, 2006 will be remembered as the year British biotechnology took the first step towards an authentic cure for spinal-cord injury in  humans, with a promise of greater things to come. He aims to do this not with cells taken from embryos, but cells from high in the nose of a spinally injured patient. It’s a procedure, he claims, that can be applied to damaged optic nerves and deficits from stroke injury, such as loss of speech, hearing and movement. The plausibility of his proposal is in the fine detail: the relentless experiments, clinical trials and scientific papers that constitute his life project.

There have been other bids to use nasal cells for spinal-cord therapies, in Lisbon, Rio and Shanghai; the results have been ambiguous and short-lived. Raisman explains that, unlike most other attempts, his research programme has scientific depth and depends on monitored trials that eliminate chance dramatic remissions and slight improvements prompted by physiotherapy.

Raisman does not see himself in a race with these other attempts to exploit nasal cells, nor do any of his rivals. As he says, “Elsewhere, doctors are using nasal cells as a shot-in-the-dark treatment rather than as systematic, scientifically based trials.” His work has been acclaimed by top peer-group scientists.

Alastair Compston, a professor of neurology at Cambridge and the editor of the journal Brain, says: “Raisman is the business! His proposal has emerged from meticulous, step-by-step basic science.”

Professor Tim Bliss of the National Institute for Medical Research (MRC) echoes the verdict: “Raisman stands for scientific integrity. If anybody can pull it off, he will!” The head of the MRC, Professor Colin Blakemore, recently hailed Raisman’s laboratory work on rat and mouse models: “He has effected the first and only demonstration of breathing with high spinal lesions and has developed this work right through to the stage of clinical trials.” Last year Raisman won the coveted Christopher Reeve gold medal for research into spinal-cord injury.

Raisman’s proposal finds its origins in the vast, mysterious environment of the nerve cells, or neurons, of the brain and the central nervous system. We are born with over 100 billion neurons, the biological computing mechanisms that regulate thought, action and sensation. They send and receive messages that control the entire organism of the body. It has long been known that, apart from those extraordinary olfactory nerve cells in the nose, neurons do not replicate or regenerate when they die: you only ever lose them. But you have a lot to lose, and the loss of neurons is often compensated for by the flourishing growth of neighbouring neuronal branches known as dendrites, which take over the space vacated by a deficit.

Neurons send and receive their signals through myriad branch-like nerve fibres. They communicate with their neighbours by firing chemical substances across minuscule terminals known as synapses. There are more combinations of signals in the massed neuronal undergrowth than there are particles in the known universe. Neuronal signals are strengthened when we learn skills, such as a language or a new sport. Those neurons we fail to use atrophy and eventually die. Raisman tells me that when he gazed at neurons and their nerve fibres through an old-fashioned light microscope, they appeared motionless, “like a forest of trees, silent in a windless sky”. But when he first observed them through an electron microscope (with orders of magnification in the millions), “it was like snorkelling through a kelp forest… All was in a state of flowing motion… continual change”.

As he gazed into this jungle of the brain and central nervous system in the mid-1960s, he was inspired to propose his theory of “plasticity”: the first step in his bid to mend a broken spinal cord.

When a neuron dies, the synapses decay  and break down irretrievably. But then the  nerve fibres of neighbouring healthy neurons sense a vacuum and extend new branches to compensate. Raisman likes to compare this phenomenon to a Hindu god with many arms and hands. “Losing a neuron is like the god losing an arm and accompanying hand. But it’s as if a neighbouring arm sprouts new hands to make up for that loss.” He gives me another image: “Imagine a ring of dancers holding hands. One drops out and the ring is broken until the dancers on either side join hands around the empty space, completing the ring again.”

Raisman’s theory of neuronal plasticity was not well received in the 1960s, because it challenged a sacred cow of neurology. When neuronal connections in the
spinal cord are lost, by falling off a horse, say, like the late Christopher Reeve, scar tissue forms at the site of the break and the affected neurons die. Neurologists were once convinced that the devastating effects of spinal-cord injury, which can involve all bodily functions, including breathing, were not just the result of the barrier caused by scar tissue, which quickly grows at the site of the damage, but were simply due to the fact that neurons lost in an accident are never replaced. Yet now there was Raisman’s plasticity bombshell: “The neurons don’t grow back,” he declares, brightly, “but the branches of the neighbouring healthy neurons move in to take their place.”

So why do these new connections fail to link up with their corresponding partners on the other side of a scar? Is it because of the density and hostile environment of scar tissue? Or are there other factors? Raisman’s answer – discovered in the nerve cells of the nose – lay more than 20 years ahead. Meanwhile, he sat on his controversial idea of plasticity: “It’s amazing how unwilling the world is to accept new ideas, even when they are positive ones.”

He published his plasticity paper in 1969, and in 1978 wrote an article entitled What Hope for Repair of the Brain? His life’s work lay before him.

Raisman’s scientific personality – maverick and obstinate to the point of obsession – was shaped by his background and confirmed by his behaviour in early manhood. Born in 1939, he was the only son of a deaf Jewish tailor, whose family, headed by a notorious gambler, had come from Lithuania to the north of England in the previous generation. Raisman’s father was earning just £3.50 a week in the 1950s in the sweatshop tailoring factories of Leeds: a wage equivalent to about £5,000 a year today.

His father had a sense of poetic wonder for the natural world. “When I was a child,” Raisman says, “he would take me up onto the hills near Leeds and dig his hands deep
into the soil. ‘Feel the warmth of the soil, Geoff,’ he would say.” Geoff’s father wanted his son to be a doctor.

Raisman is fiercely proud of his upbringing in working-class Leeds. Its influence often shows in his indignation when he perceives members of the medical profession to be patronising their less well-educated patients. “I mean, the sort of consultants and medical scientists who refer to a sick boy as Mrs So-and-So’s Little Willy.”

Raisman passed the 11-plus, attended Roundhay grammar school, Leeds, and won a scholarship, aged 17, to Pembroke College, Oxford. Intrigued by the hieroglyphics of ancient languages, he had wanted to read archeology. His father, who made him his first suit to take to university, persuaded him to read medicine. “I had always shared a bed with my uncle Myer at home,” says Raisman, “but now for the first time I had a bed to myself and a servant to make it and to wash my dishes.” Shortly after arriving at Oxford, though, he broke with the strict convention of the time to marry Vivien, his childhood sweetheart.

They were just 18. His father was devastated, suspecting that Geoff would now drop out. The college authorities were also angry and withdrew his scholarship. But Raisman was obdurate: “They didn’t seem to appreciate the drive of my endocrine glands!” he muses. He successfully applied for a grant from his local authority, and his young wife gave up her university place in Edinburgh and came down to Oxford to work as a secretary to help keep them. They lived in one room out on Headington Hill.

Today, Raisman talks of his devotion and debt to his father and Vivien, and to his first anatomy and physiology tutors at Oxford. One of them, Max Cowan, a leading facilitator in post-war British biotechnology and the son of a miner, saw his student’s potential as a serious scientist and set him on the path to a doctorate in neuroscience. The other, his anatomy teacher Percy O’Brien of Pembroke College, was “a fiery little Irishman”, brilliant but eccentric. “Like one of those Buddhist teachers,” says Raisman, “O’Brien would punch me in the chest for emphasis during tutorials… When he spoke to Vivien, though, he used to hit her over the head.”

Raisman qualified as a doctor, but instead of practising and immediately improving his financial prospects, he stayed on at Oxford as a research neuroscientist, working on the hippocampus – the seat of memory. He played an important early part in the theory, correct as it turned out, that certain kinds of memory are the result of strengthened signals in the neuronal connections of this tiny part of the brain. As soon as he started to earn a salary, Vivien went to university herself and gained a double first in Hebrew and archeology. In the 1970s they had a daughter and moved to Hendon, north London, where they live today. Vivien became a distinguished expert in Egyptology, which she now teaches at London’s City University.

By 1979 the “fury”, as Raisman calls it, against his principle of plasticity had died down. One day it would become a hallowed section in neuroscience textbooks. “I often enjoy a secret inner smile,” he says, “when some earnest young student explains Raisman’s theory of plasticity to me.” The question now was how to exploit the knowledge clinically – but there was still that paradox: the failure of the spinal cord to penetrate the scar tissue that forms after injury.

There are many theories about this riddle. Some researchers believe the problem lies with the impermeability of the scar tissue. Others propose the lack of a neuronal fertility booster, a “nerve-growth factor”, in the injured spinal cord. Another theory argues that, following injury to the spinal cord, certain molecules emerge to inhibit the growth of nerve fibres. “But what,” says Raisman, “if the problem is the lack of a conduit to guide the new growths of nerve fibres to their proper destinations?”

He eventually found confirmation of this idea – in the nose. Studying olfactory neurons – the principal sensors responsible for smell – Raisman focused on their unique ability to die and regenerate. “The evolutionary advantage of this constant death and regeneration is that, unlike other sensory neurons – sight and hearing, for example – the olfactory neurons have direct contact with the environment. They are constantly and directly battered by exposure. If they did not die and regenerate, you’d lose your sense of smell the first time you had a cold or breathed in smoke.”

After years studying these nasal neurons, Raisman came to understand what he believes to be their secret. When the regenerated neurons sprout new branches, or
nerve fibres, in the nose, they are steered to their connecting goals in the brain by pathways. These pathways, or conduits, are essential to the successful regeneration of olfactory neurons, and they emerge from stem cells stored in tissue high in the nose. They are known as olfactory ensheathing cells (OECs) and belong to a class of cells known as glials (“gluey” cells). The glials owe their guiding potential to their shape: they have tiny porous canals, like a Cadbury’s Flake bar, through which the new nerve fibres grow and seek their corresponding partners across the gap or injury site.

Raisman’s plan was to collect the young glial stem cells from the mucous lining of an injured patient’s nose. After a short period of culture, during which they would proliferate and be cleansed to avoid infection, he would graft them into the damaged site in the spinal cord in the hope that they would now guide the nerve fibres on either side of the scar towards each other. Unlike the innumerable disappointments of similar bids in the past, there is abundant laboratory evidence that his strategy works. The mechanism behind it, he believes, has been demonstrated repeatedly.

“The grafts of nasal cells,” he says, “do not simply penetrate the scar tissue: they interact in complex ways with the scar’s cells, known as astrocytes – which are living, not dead. The graft persuades the cells of the scar to open up, making room for the new pathway. Imagine a revolution where the railroad tracks are pulled up and piled up as a roadblock: it’s as if the graft works to allow the tracks to be put back in place.” Raisman likes to compare spinal-cord injury to a motorway, where a stretch of the road has been washed away. “The drivers, the nerve fibres, still remember where they are going, and there is nothing wrong with their cars. There’s no
point in replacing the vehicles, or giving them more petrol, or setting up green ‘go’ lights. What we need to do is rebuild the pathway.”

By the early 1990s, Raisman had assembled  a group of “pathway” scientists at the MRC laboratories at Mill Hill, north London. They included two women Chinese researchers,  both named Li, as well as a Korean, an Eritrean,  a Swede, a Japanese, a Greek Cypriot and a Brit. He had met the Lis in mainland China after
the end of the cultural revolution. Fascinated by oriental languages, he had learnt Chinese and Japanese and was frequently travelling to laboratories in those countries. His Chinese became good enough to give lectures in the language and quote Chinese poems to illustrate a point in an argument.

At Mill Hill he started transplanting glial cells into parts of a rat’s nervous system where a lesion had been artificially induced. “The results were beyond our wildest dreams,” he says. “First, the cells survived transplant. Second, they opened up the pathway, allowing the growth of severed nerve fibres.” Returning to his motorway analogy, he declares: “The transplanted cells had repaired the road: a bridge had been thrown across the destroyed section of motorway and the cars were driving across it. Most important of all, the transplanted cells had restored function.”

Raisman never forgets the day he first realised that his pathway hypothesis had worked. “It was in the depths of winter. I had gone to examine my rat model at 2am. My breath was like steam in the frozen night air.” The rat, with an artificially induced lesion preventing movement of its left paw, had been treated with a graft of nasal glial cells from its own nose.

“I offered it some food, and could hardly believe my eyes. It put its left paw forward. For a moment we looked at each other in shocked surprise. Then it took the food. It was a moment that occurs maybe just once in a scientist’s lifetime – if you’re very lucky.” Since then, Raisman and his team have treated similar injuries in rat models dozens of times, including mending the part of a rat’s spinal cord that controls breathing.

Now the time has come to work on human patients. In December 2005, Raisman moved his team to a facility in Queen Square, London, under the auspices of the Institute of Neurology and University College London.

Essential to his plans is the involvement of the neurosurgeon Professor Tom Carlstedt, renowned for his work on the human spinal cord. They have permission for the first preliminary safety study, which begins this autumn.

The team aims to mend a collection of injured nerve fibres at a point known as the dorsal root, where nerve fibres emerge high in the spinal cord and into the shoulder. The site – the brachial plexus – is often severed in traffic accidents, especially when bikers take a tumble, landing on their shoulders. The consequent injury, known as a “brachial plexus avulsion”, results in a paralysed arm and acute pain. “It’s as if the still-living fibres are putting out a mass of white noise,” Raisman says.

“The pain is so great, the patient sometimes becomes suicidal.”

The surgeon will retrieve olfactory ensheathing cells from the patient’s nose. Being autologous – in other words, containing the patient’s own DNA – there is no likelihood of rejection. First the cells, numbering about a million, but collectively as small as a pinhead, will be cultured before being grafted into the site of the break by two surgeons and their teams. Within several weeks it is expected that these glial cells will have created the desired pathway for the severed nerve fibres to grow through, and that normal sensation and movement will be restored. “From here,” says Raisman, “the way is open to evolve techniques for repairing larger spinal-cord injuries of the type that Christopher Reeve suffered. In the more distant future, we’ll be able to repair damage to the optic nerve that causes blindness, and brain injuries of the type endured in strokes, causing deafness and loss of speech.” The treatment process will be the same.

Where the injury has been caused by a disruption of the nerve-fibre pathways – in the optic nerve, for example – the patient’s own olfactory glial cells will be surgically grafted into the site in the expectation that damage will be repaired. “We believe,” says Raisman, “that the nasal cells can act as bridges, allowing regeneration of severed nerve fibres in any part of the brain or the central nervous system.” 

He admits there is a limiting factor, “where the grafts would not be long enough to create a bridge all the way between undamaged areas”.

Raisman is cautious about the details of such alternative prospects to spinal injury, but he insists that there is no difference in principle between providing new pathways for nerve fibres damaged by stroke (resulting in the inability to speak, or to hear) and mending the nerve fibres in the brachial plexus.

Getting to know Raisman and his work over a period of several weeks involved reading a quantity of the 300 technical papers he has written in the past 40 years. Most relate to his original discovery of that property he calls plasticity of the brain and central nervous system. As I talked with him in his lab high up in the concrete skyscraper that houses the Institute of Neurology in Holborn, or walking round Queen Square below, I was struck by his lifetime’s concentration on what seemed to me such a narrow focus of neurophysiology. “Don’t you ever get bored with the sheer confinement of your preoccupation?” I asked him.

Raisman was amazed at the narrowness of my perspective. “Observing the plasticity of the nervous system,” he said, “is a keyhole into a universe of extraordinary, never-ending wonder… You don’t stop at the cells and the molecules, you are gripped by the extraordinary complexity of nature’s imagination.” If Raisman fails, it is more likely to be because of his dogged refusal to become involved with attempts to patent his discoveries. A token of his maverick “bloody-mindedness” is his determination to give away freely the intellectual property rights of his procedures.

Unlike most other spinal-injury research, he has no links with the pharmaceutical industry or prospective income from private treatments. “We have no funding from any research council, from any university or from government,” he told me. “Everything comes from my efforts with charities and in finding benevolent donors… and we have just enough funds to sustain the team beyond three years.”

The procedures – 10 of them – to be performed in September will be done on the NHS, and he refuses to put a price tag on them beyond informing me that his laboratory costs are currently running at £500,000 per annum. As he tells me this, he appears totally relaxed, and I remark upon the fact. “The point is, I’m a scientist, not a doctor. When patients come to a doctor they are looking for treatments. They are often desperate and the doctor can be affected by that desperation. It’s different for me: I’m a researcher involved in trials, not treatments. It sounds harsh, but just because a patient is desperate does not mean I should be desperate.”

In an area of scientific medicine increasingly beset by desperation to the point of fraud, Raisman’s programme looks like an oasis of quiet, scientific optimism. Was he not worried, I asked, about the prospect of failure? “If we get even part of the way,” he replied, “or if we fail,   even our mistakes might be useful. That is the difference between a trial and a treatment.”

Raisman and his team, however, do not have the look of scientists who are about to fail.

[Christopher]

Here's a good discussion about this article on a very informative SCI (Spinal Cord Injury) site. The site's founder is one of America's leading neuroscientists, Dr. Wise Young. And he replies to this post as he does to many. Fantastic resource for up and coming research and science news!

http://carecure.org/forum/showthread.php?t=61447

[jennyb]

Fantastic article Christopher, I didn't know Raisman came up with the plasticity theory 40 odd years ago! How refreshing to read about doctors who are in it for one reason, and one reason only-the patients. I hope they get the success they deserve-it's also very different from the secrecy surrounding the Korean doctor experimenting with stem cells who later was exposed as a fraud, as mentioned in this article - I saw his website and it was impressive, although a bit thin on facts, high on glitz. Just goes to show you can't judge doctors by what they say about themselves on websites-I know of people who were prepared to travel to that guy for treatment!
Really good to read of real doctors who make a real difference, and who are prepared to share their work for the good of all SCI and BPPPI patients, hats off to these guys. Maybe the first bpi fixed this way will be one of our tbpi uk guys-several have Carlstedt who works with Raisman as their doctor.
Here's hoping..........:0)
Jen NZ

[Christopher]

Well, I hate to say it, but these trials where hoping to start 2 years ago. Now it is reported for another 1-2 years from now. I imagine has lots to do with funding as usual. I saw video of rats, that Prof. Raisman had worked on, with avulsed nerves that were re-implanted successfully and able to use their injured limb 4 years ago.

I guess I better start making my millions today if I want to bring about change! Hup two!



http://business.timesonline.co.uk/tol/b ... 904111.ece
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The Times
May 10, 2008

Spine injuries maybe repaired by a nose
Simon Midgley

Geoffrey Raisman, a renowned British neuroscientist, has never forgotten the day he first realised that his hypothesis on how severed spinal cord nerves could be repaired just might be correct.

A rat had been prevented from moving its left paw by a lesion in its nervous system. Cells from its nose had then been grafted into the lesion in the hope that they would grow across the gap in the nerve pathway and restore function.

Offering the rat some food in the middle of the night, Raisman could hardly believe his eyes when it put forward its left paw to accept the morsel. It was, he has said, a once in a lifetime moment.

Raisman, director of the Spinal Repair Unit at University College London Institute of Neurology, leads a research team whose work could ultimately lead to the repair of spinal cord injuries in humans. An estimated 40,000 people in the UK live with spinal cord injuries. His team’s work offers significant hope that such patients will eventually be able to regain much lost movement.

For paraplegic patients – those with impairment of the functions of the lower body – this could lead to a return of sensation and movement to some leg muscles which could allow them to stand and move.

Tetraplegics – patients whose arms are also affected – might be able to recover touch sensation, movement of the hands and the ability to dress, feed and clean themselves.

Raisman’s key discovery was that there is one part of the nervous system – nerve fibres in the nasal cavity – that continually renews itself. If his experimental work with rats can be replicated with humans then patients could become their own cell donors.

In the next year or two the team is hoping to conduct a preliminary safety trial of the technique at the National Hospital of Neurology and Neurosurgery in London. Initially they will use nasal cells to try to repair nerves torn out of the spinal cord in motor bike accidents. “In the long run,” he says, “We hope this will get people out of wheelchairs.”

[Ripp]

This is fascinating! I'd love to be first in line for the tests on people instead of rats. I imagine most of us would line up to let him give his theory a try.

[admin]

Have these trials still not taken place?

[Christopher]

Not that I know of. I check Dr. Raisman's website about once a month.

If I discover that they ever start, I'll post it here.

[swhite1]

Once again Christopher you have presented us(BPI'ers)with a glimmer of hope. Actually just more of the tools for us to hope. In the end it is up to us as individuals to either hope or despair. I prefer to just carry on and one way or another something will help...or it won't.
I do try to stay humored(???)by it all. For instance in para. 16 I believe it was where Prof Raisman refers to the Hindu god's many ARMS and or HANDS. That was code for us(BPI'ers)to keep our heads up, help is on the way.
Compared to para.39 - “The pain is so great, the patient sometimes becomes suicidal.”
Am I the only one who has thought this and just as quickly thought better? You know Hell will be all this and more right.
I did not note the paragraph of this one but he also mentions when neurons die they take with them a memory.
Have you ever smelled something that reminded you of something else? Is this what he's talking about? Or is he stating that when neurons die they take with them a memory like 2 + 2 = ...? Does this all mean that when we sneeze we can lose years of memories that are linked with nasal neurons???
Hmm. Makes you wonder right? Makes you think am I(me, Scott)am I for real or am I just tongue and cheeking...lol.
Peace out, and thanks again Christopher another good one.
Scott

Which web site to keep up with Dr. Raisman's research is the most recommeded? There are quite a few.


Message was edited by: swhite1