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Michelle Mullen had it all: good job, money, and a busy social life. Then she went to her doctor with numbness and blurred vision, and everything changed ...

Until five years ago, my Friday nights tended to follow the same pattern. I would be partying hard at the Sanderson or Toast, hanging on to a cosmo with one hand and a Silk Cut with the other. Business was great, my world found me funny, gorgeous, entertaining and, oh yes, did I mention smart? I liked to think I was the epitome of modern woman: independent, vibrant, successful and nobody's fool. I loved life and it loved me.

It was on the Monday morning following one of these Fridays that I found myself in front of a GP I had never had cause to see, with a severe case of sudden double vision and a numb arm, only to be told with considerable condescension that I was an alcoholic at 29. I admit I liked a drink as much as anyone, but you would not catch me splattered across the front pages of the Sun, my skirt tucked in my knickers, staggering along Croydon High Street on Saturday night.

So I sat opposite my GP in a tiny, white room with the latest government health poster on sexually transmitted diseases hung distractingly behind her while she thumped the reflex hammer she had just whacked off my knees against her desk. She suggested I was an alcoholic on the back of one or two business lunches a week and as many nights out. I gave her medical expertise 30 seconds' serious thought before leaving the surgery deflated and without so much as a prescription for how to deal with sanctimonious doctors. Two weeks later, and nearly £1,500 poorer, I was staring at my MRI scan while a private neurologist told me I had multiple sclerosis. I knew it wasn't the drinking - so somebody pour me a glass.

Despite the shock of the diagnosis, my initial concern was for my twin. I wanted him to be unaffected. We were, and are still, very close. He is my rock and when I start to slide towards negativity and self-limitation, he has a wonderful way of giving me a good kick (some things haven't changed). He was the first person I told. Calm and positive, and privately devastated, he responded to the news by arriving at my door with a bottle of Bolly and more cigarettes. In contrast, when I told my partner of four years, he asked if he should stay as my care partner. Hello? I hadn't realised there were any plans to leave. It was the beginning of so many ends and the start of a very different life I had never asked or planned for.

At the time, I ran my own business commissioning music for broadcast (and two other companies belonging to my business partner), worked out every day, including three-mile runs around the Serpentine and went to two sessions a week of wildly strenuous capoeira. I drove a shiny, silver Mercedes SLK (how I miss those heated seats, but hey, they only give you piles anyway), had my West End apartment and an apartment in France - not bad for a hard-working girl from a broken home and a council estate.

Within 18 months my partner had left, and my relationship with my friend and business partner had broken down too. I was rapidly sliding into a depression marked by bouts of heavy drinking (my GP should have seen me then!). Driven by a gut instinct that there was more to life than profit and cosmopolitans and a sense that this downward spiral of self-abuse would end very badly, I decided I could no longer continue with the business and one day literally lay down the office and car keys on my desk, said goodbye to the staff and limped away; my foot had just started to develop a neurological drop. Many people with MS claim they never succumbed to colds or viruses and certainly that was my experience. I still think that I was born a superhero, just that someone has nicked my powers of late. The reality of living with the disease, however, has been quite different. I have not had the good fortune of a benign or occasional flare-up of MS, but an active, petulant, will-not-be ignored, relapsing-remitting kind. It has chipped away at me on each visit, leaving deficits and a bewildering sense of "Where will it end?". I have not run for more than two years. I use a walking stick, though lately it's bilateral crutches as my legs refuse to work from the knees down (I have foot drop, which means that the foot drops and does not pick up off the floor properly), and numbness and ataxia of the right leg and arm. Just great when a very hot bath feels freezing and doing your makeup is a feat comparable to a specialist performing open-heart surgery. Did I mention the spasticity that means I shuffle like a robot? Or the fatigue? I feel as if I have gone 10 rounds with Mike Tyson just trying to put my knickers on.

Diagnosis, as is common, came at the prime of my working life. At that age, permanent health insurance, mortgage protection and critical illness cover just do not feature in your monthly outgoings list. They certainly didn't in mine - I'll have another cosmo please, or how about the latest Louis Vuitton handbag? Life cover became as expensive as a mortgage.

Two months later I had moved back home to my parents and rented out my property, only to be told by the employment office that I was not entitled to any help beyond six months' jobseeker's allowance. I would need to sell my home to qualify but even then I would be expected to live off the equity first, so I spent a year living off my savings and trying to work out what I was going to do. Eventually, the savings ran out, and when I was no longer footing the bar bills my friends drifted off. I ended up temping for a while to keep my head above water. These days, I have what I like to call a "portfolio career". Encouraged by my twin, I have gone back to doing what I love and never had time for - making music, rather than selling other people's - and I have started to write. To pay the bills I work part-time in a bank.

Like so many young people with MS, my career prospects seem to have hit a wall. Fatigue limits the hours I can work and my sick record is not pretty (although my usually sympathetic boss seems strangely pleased by my latest symptom, a numb mouth). When I did ring the disability employment adviser, set up by the government to get more disabled people back into work, to explain that I needed a job that involved less mobility, the person on the other end of the phone wailed, "Michelle, there just aren't jobs out there for 'normal' people, let alone people like you." People like me? Hmm, I'm not sure what she meant by that but can only assume: superhuman, intelligent and sexy.

I want to put a positive spin on this but there are enough jolly articles on the internet about miracle cures and "I became a better person with MS" stories put out by the various MS organisations. I didn't become a better person. I have become a considerably poorer, more humbled, frightened person. I am in my early 30s. I do resent losing the capacity for personal grooming, to earn a good living, to be a pop star or athlete (if I wanted). And more than anything, I resent having fewer choices.

But a couple of years ago, I did meet someone wonderful in a recording studio. Cris is a music producer who encourages me to be creative, and to be the best I can, to live in the now and whose love has proved unconditional. More importantly, Cris took me on with MS and makes me feel that I'm perfect as I am, even though my body - and possibly my future - so clearly isn't.

Finally, after friends, lovers and others ran out at the beginning, I can still type and read. Small pleasures for my simple world, so maybe I did become a better person after all. But I still think MS sucks.

http://society.guardian.co.uk/health/comment/0,,1974433,00.html

 

Embryonic Stem Cells Awaken Latent Nerve Repair

JHU scientists engineer working motor neuroncircuits in paralyzed rats

By Marjorie Centofanti
Johns Hopkins Medicine
In a dramatic display of stem cells' potential for healing, a team of Johns Hopkins scientists reports that it has engineered new, completed, fully working motor neuron circuits - neurons stretching from spinal cord to target muscles - in paralyzed adult animals.

The research, in which mouse embryonic stem cells were injected into rats whose virus-damaged spinal cords model nerve disease, shows that such cells can be made to retrace complex pathways of nerve development long shut off in adult mammals, the researchers say.

"This is proof of the principle that we can recapture what happens in early stages of motor neuron development and use that to repair damaged nervous systems," said Douglas Kerr, a neurologist who led the Johns Hopkins team.

Elias A. Zerhouni, director of the National Institutes of Health, which provided a grant for the study, said, "It's a remarkable advance that can help us understand how stem cells can begin to fulfill their great promise. Demonstrating restoration of function is an important step forward, though we still have a great distance to go."

The researchers created what amounts to a cookbook recipe to restore lost nerve function, Kerr said. The approach could one day repair damage from such diseases as ALS (Lou Gehrig's disease), multiple sclerosis and transverse myelitis, or from traumatic spinal cord injury, the researchers say. "With small adjustments keyed to differences in nervous system targets," Kerr said, "the approach may also apply to patients with Parkinson's or Huntington's disease."

In a report on the study, released online today, June 26, in the Annals of Neurology, the Johns Hopkins team says that 11 of the 15 treated rats gained significant, though partial, recovery from paralysis after losing motor neurons to an aggressive infection with Sindbis virus - one that, in rodents, specifically targets motor neurons and kills them. The animals recovered enough muscle strength to bear weight and step with the previously paralyzed hind leg.

Kerr likens the approach to electrical repair. "Paralysis is like turning on a light switch and the light doesn't go on," he said. "The connectivity is messed up, but you don't know where. We've asked stem cells to go where needed to fix the circuit."

For a brief period after a nerve dies, it leaves behind what's essentially an empty shell, with some scaffolding and non-nerve substances remaining. "But with [embryonic stem cell] injections at the right time and place, and by adding the right cues, we've learned to restore the biological 'memory' for growing neurons, which is clearly still in place," he said.

The motor circuit engineering combines recent discoveries on stem cell differentiation, a growing understanding of early development of the nervous system and insights into behavior of the nervous system in traumatic injury, Kerr noted.

"As adults, our cells no longer respond to early developmental cues because those cues are usually gone," Kerr said. "That's why we don't recover well from severe injuries. But that's what we believe we have changed. We asked what was there when motor neurons were born, and specifically what let motor neurons extend outward. Then we tried to bring that environment back, in the presence of adaptable, receptive stem cells."

In the study, Kerr's team pretreated cultures of mouse embryonic stem cells with growth factors that both increase survival and prompt specialization into motor neurons. Adding retinoic acid and sonic hedgehog protein - agents that direct cells in the first weeks of life to assume the proper places in the spinal cord - readied the conditioned embryonic stem cells for the motor neuron circuit that starts in the spinal cord. Then, stem cells were fed into the paralyzed rats' spinal cords.

Extending new motor neurons in an adult nervous system, however, meant overcoming hurdles. One involved myelin, the fatty material that insulates mature motor neurons. Like the coating on electrical wire, myelin prevents weakening of the traveling electrical impulse and lets it continue long distances. In humans, the myelinated sciatic nerve, for example, exits the spinal cord and extends to the leg muscles it activates, carrying impulses several feet.

Once laid down, however, myelin inhibits further nerve growth - nature's way of discouraging excessive wiring in the nervous system.

"We had to overcome inhibition from myelin lingering in the dead nerve pathways," Kerr explained. Two recently developed agents, rolipram and dbcAMP, enabled that.

The assorted treatments let the new motor neurons survive, grow through the spinal cord and extend slightly into the outlying nervous system. A second hurdle remained in getting the neurons to skeletal muscle targets.

As suggested by earlier work by team member Ahmet Hoke on repair in the outlying, peripheral nervous system, the researchers applied GDNF, a powerful stimulator of neuron growth, to the remains of the newly dead sciatic nerve at a point near its former leg muscle contacts. GDNF attracted the extending motor neurons, "luring" them to the muscles.

To ensure a continuous supply of GDNF, the researchers relied on injected fetal mouse neural stem cells, a known source of the molecule.

Of some 4,100 new motor neurons created in the spinal cord, roughly 200 exited the cord and 120 reached skeletal muscle, forming typical nerve-muscle junctions, with appropriate, typical chemical markers.

Microscopically, the neurons and their muscle associations appear identical to natural ones in healthy animals.

Fifty of the new neurons were found to carry electrical impulses.
(Because such testing is time and labor intensive, only a small area of leg muscle was assayed. The improved ability of treated rats, however, suggests more functional neurons are likely.) The rats gained weight and were more mobile in their cages, and measures of muscle strength increased.

Animals treated without even one component of the "cocktail" experienced no such recovery. Novel ways of tracing the neurons back to their source assured the scientists that they indeed had come from the injected stem cells not from lingering host neurons.

Research begins this summer to see how well the technique applies to human nerve recovery, using federally approved human embryonic stem cells in larger mammals like pigs, Kerr said. Each of six academic institutions in a new collaboration will tackle a different major question of safety and effectiveness. Questions of tumor formation, often a concern with embryonic stem cells; of the safety of surgery; and of the embryonic stem cells' ability to form healthy motor circuits are major questions to answer. Several years of testing and thorough data evaluation would occur before applying to the FDA to approve human clinical trials.

The study was supported by Families of SMA, Andrew's Buddies/Fight SMA, the ALS Association and the Robert Packard Center for ALS Research at Johns Hopkins, the Muscular Dystrophy Association, Wings Over Wall Street and a grant from the NIH.

Kerr is a grantee of the Packard Center for ALS Research at Johns Hopkins. He also directs Project RESTORE, a Johns Hopkins-based undertaking to advance therapies for transverse myelitis and multiple sclerosis.

This video shows a rat with his hindlegs paralyzed from Sindbis virus. He's received the full "recipe" of embryonic stem-cells, myelin-inhibition overcoming and neural stem cell-based growth factor release on both sides of his body. It's 5 days after treatment.

This video shows the same rat after four months.

Others on the research team from Johns Hopkins are Jeffrey Rothstein, Hoke, Nicholas Maragakis, Yun Sook Kim, Sonny Dike, Deepa Deshpande, Chitra Krishnan and Jennifer Drummond, all of the Department of Neurology at the School of Medicine; and Jessica Carmen, Tara Martinez and Irina Shats, all of the Department of Molecular Microbiology and Immunology at the Bloomberg School of Public Health. Jeremy Shefner, of the Department of Neurology at the State University of New York Upstate Medical University, also contributed to the study.

http://www.hopkinsmedicine.org/Press_releases/2006/Mousevideo.html