MadWire

Stem Cell Advisory: Buyer Beward

maddogz — Sat, 13 Dec 2008 04:39:00 GMT

Cautionary stem cell tourism guidelines came out earlier this month, taking aim at overseas clinics characterized by unsupported expectations, overhyped therapies and uninformed risk.

The new guidelines originated from the International Society for Stem Cell Research. (Mission statement: “an independent, nonprofit organization … to promote professional and public education in all areas of stem cell research and application.”)

From a press release: “The ISSCR is deeply concerned about the potential physical, psychological, and financial harm to patients who pursue unproven stem cell-based ‘therapies’ and the general lack of scientific transparency and professional accountability of those engaged in these activities.”

In other words, the stem cell field is worried about people getting ripped off or getting harmed. They are also worried about the bigger picture. This is from a piece on Bloomberg:

“We’re worried about patients and we are worried about the field,” said George Daley, a researcher at the Harvard Stem Cell Institute and member of the task force that wrote the guidelines, in a telephone interview. “The field is at risk from renegade, illegitimate practitioners. If there is a public perception that the science isn’t being done carefully then we’re at risk for losing public support.”Of course anyone considering a trip to India or China or to any of the countries that offer stem cells should read this material and take it seriously.

Of course even though this represents the considerable opinion of the world’s cell biology brain trust, the guidelines may do little to deter those who see no hope in the choices of approved therapies available at home, and who have little patience that the U.S. stem cell promise will be realized any time soon.

I didn’t find much buzz about the latest stem cell caveat emptor at the Internet cure hangouts. The news was pretty well disseminated by the mainstream media, with some pithy headlines, like these:
Beware of Bogus Clinics Offering Stem Cell Cures
"Rogue" stem cell clinics exploit hope: report

An ISSCR team from 13 countries drafted the guidelines over the past year and honed them into two documents, Guidelines for the Clinical Translation of Stem Cells, which looks at the scientific, clinical, regulatory, ethical and social justice issues that must be ironed out to move basic stem cell research toward clinical applications.

Simultaneously, the group released a consumer-oriented Patient Handbook on Stem Cell Therapies. This is the one to read if you’re thinking about getting shot up with stem cells – it sets forth a primer on stem cells and their limited use, on how clinical trials work, and asks the questions that must be answered to know whether you are getting an expensive and exploitative experiment or a real therapy.

The ISSCR suggests this checklist for people considering a trip abroad for stem cells. Ask for:

Evidence of published pre-clinical studies that have been reviewed -- and repeated -- by experts in the field (need it be said, these peer reviewers aren’t allowed to work for the clinic).
Evidence that the provider has ethical approval from an independent committee (Good luck with this in China or India).
Evidence that the provider has national or regional regulatory approval. In the UK, this is the European Medicines Agency (EMEA).

The ISSCR warns that certain claims made by providers of stem cell therapies should sound alarm bells:

Claims based on patient testimonials (this is the basis of all Internet hopefulness; self-reported effects of any treatment are notoriously inconsistent and unreliable).
Claims that multiple diseases or conditions are treatable with the same cells (there is no cell line or cell cocktail that is the universal treatment for say, Parkinson’s and heart disease).
Claims regarding the source of cells or treatment details (you might want to know how well screened the cells are for viruses and pathogens – also, where exactly did they come from).
Claims that there is no risk. Note: there is risk rolling into a foreign clinic; there is risk with any surgery, with any injection.
High cost treatments or those where the true cost is hidden.

Until the overseas stem cell clinics answer basic questions, they must be considered human laboratories. If the treatments do indeed work, the medical technology must be shared. It’s up to the clinics to make their unsavory reputations go away. Kudos to ISSCR for taking a strong stand.

Mad

A drug to fire-up your patterns?

maddogz — Tue, 02 Dec 2008 18:54:00 GMT

The recent Society for Neuroscience meeting in Washington, DC, showcased a huge range of work that, in the whole, leaves little doubt that regenerative medicine and functional recovery are moving forward.

(A tip of the MadWire hat to Steven Edwards, a C3 quad from South Carolina and a moderator for the CareCure community who compiled a long list of the SCI related papers.)

Even if you have little tolerance for the academic nature of the writing, it’s possible to tease out quite a bit of optimism from Edwards’ list. Here is a paper that caught my eye, a) because it’s aggressively intended to go to clinic soon; b) it was funded in part by the Reeve Foundation; and c) because it sounds like a pill to make you walk.

The formal title is “Pre-clinical and clinical development of a drug treatment for Central Pattern Generator (CPG) activation and 'reflex' stepping induction.” A group from Quebec led by Pierre Guertin began with the body of evidence that stepping motions in paralyzed animals are controlled not by brain input but in the spinal cord by a central pattern generator.

The role of the CPG is central to the field of activity based rehabilitation (e.g. the Reeve Foundation NeuroRecovery Network, which has in many people been able to activate the CPG with repetitive stepping patterns using weight-supported treadmill therapy).

Guertin, who has already set up a company in Quebec called NeuroSpina Therapeutics Inc. to take his early lab results to the clinic, went fishing for the molecular basis of CPG activation. Using a mouse model his group tried what he calls “a plethora of serotonergic, glutamatergic, adrenergic and dopaminergic ligands over the years.” Some of the drugs worked to induce rhythmic movements, flexion and extension, but when it came time to put weight on the hindlimbs, they had no success with true stepping.

So, using the skills of a bartender, Guertin mixed a drug cocktail (based on role of serotonin receptors) he has since patented and named Spinalon. He describes this drug as “First-in class activator of the Central Pattern Generator for locomotion. It acutely evokes, upon systemic delivery, repetitive walking movements for one hour in chronic and complete SCI subjects.” OK then, for the record, a drug to make your legs move in the pattern of walking.

Says Guertin, it appears to work. Weight bearing stepping has occurred in animals, and he’s gone on to try the drug in at least one human: “The first pilot test in patients was done recently. A monoplegic man who received Spinalon every 2 days for 2 weeks showed no atypical side effects providing first preliminary evidence of safety in men (Spinal Cord, in press).”

You might join me in wondering how a scientist can go from yet-to-be published data on humans to a full-on clinical trial, but Guertin is undeterred. People are already being recruited to test Spinalon, he says. Here's to everyone's patterns and to their continued generation.

Mad

Thank You, Sun

maddogz — Wed, 26 Nov 2008 14:30:00 GMT

Thanks be given.

There’s plenty to be thankful for. Here’s to the sun, our star, our life-source. I’m thankful it comes up everyday, and I’m grateful it does so much to keep me alive and well.

Wouldn’t you know, as I scribe this from Southern California, it’s raining. Doesn’t have much heart, this storm, but it’s wet enough to wash away ashes from recent hillside fires and steady enough to make morons out of many motorists. I don’t mean to be smug about our climatological superiority, but we Californians do get lots of sun. And unless it’s shining every single day, imperfect weather makes us cranky.

Raymond Chandler knew this as he noted SoCal’s edgy desert winds that “come down through the mountain passes and curl your hair and make your nerves jump and your skin itch. On nights like that every booze party ends in a fight. Meek little wives feel the edge of the carving knife and study their husbands’ necks. Anything can happen.”

It’s not that bad. Yet. It hasn’t even been a full day of rain. Three days and no sun, this is a state full of whiny malcontents. A week without a shadow: stay away, it’s blades and necks time.

Let’s get back to the sun. Remember rickets, the bone deformity disease? It hasn’t been a public health issue in 80 years or so, but it’s apparently making a comeback. Rickets is directly related to vitamin D insufficiency. Give kids D, in the form or sunlight, or more likely in some sort of supplement, and rickets goes away. A couple of weeks ago the American Academy of Pediatrics recommended a doubling of the daily requirement for vitamin D, from 200 units to 400.

The Academy noted that many more kids today are breastfed; breast milk has little or no Vitamin D. “Thus, at this time,” says the published paper, “it is prudent to recommend that all breastfed infants be given supplemental vitamin D3”

Interestingly, the doctors have no enthusiasm for going to the source of Vitamin D – the sun. The body easily converts sunlight into vitamin D, which isn’t really a vitamin but a sort of neurohormone related to dozens of body functions, including as the AAP admits, bone formation. A brief summary of vitamin D research would add to that more than a dozen varieties of cancer, heart disease, stroke, multiple sclerosis, diabetes, depression, chronic pain, arthritis, osteoporosis, birth defects, even periodontal disease – the data are not unequivocal but this growing body of literature is not on the new-agey fringe, either.

Fear of the sun is partly to blame. Back in the day, and not that long ago, getting out in the fresh air and sunshine was considered a good thing. Back around 1998, however, the CDC, the dermatologists and the sunscreen makers hit us with a full court sun-scare program. The sun was demonized – read the label, man, sun leads to cancer. Stay out of it.

(About the same time, autism started to show up on the public health radar. No time to dive into this but there is indeed a plausible Vitamin D theory for autism.)

Vitamin D deficiency is about to be taken much more seriously. Canadians already get the public health aspects of vitamin D: of course these are folks who don’t see the sun much for over half the year. The Canadian Cancer Society raised the daily recommended vitamin D level to 1000 units a day, “based on the growing body of evidence about the link between Vitamin D and reducing risk for colorectal, breast and prostate cancers.”

In the U.S. a group of physicians and vitamin researchers has allied to promote Vitamin D. In a call to action statement, the group calls for more research, but meanwhile, urges us to take a minimum of 2000 units of Vitamin D3. Some reputable researchers recommend 5000 units or more. There is some risk of overdoing vitamin D, leading to kidney stones; scientists recommend people get a blood test to assess their levels.

Meanwhile, get me back in the sun. You don’t want to hear any more whining from the valleys and canyons of California.

Happy holidays one and all.

Mad

Silver's Blue Light Special

maddogz — Tue, 18 Nov 2008 15:53:00 GMT

Start with algae, add light, treat paralysis.

It’s one of the coolest science stories coming out of the big Society for Neuroscience meeting this week in Washington D.C.

Scientist Jerry Silver, who sits on the Reeve Foundation Science Advisory Committee, and who got partial funding for this work from the Foundation, infected certain spinal cord neurons with genetic information from a common single-cell algae called Chlamydomonas. When activated by a flashing blue light, a part of the algae called channelrhodopsin-2 (ChR2) acts as a gate, depolarizing ion channels and thus promoting signal transmission.

Silver’s trick was to induce the ChR2 in the part of the spinal cord (second vertebrae, near the phrenic motor pool) that relates to breathing. By so doing he was able to harness the nerve signal and – to his astonishment – allow restoration of breathing function in cervically injured rats. What's more, the stimulation lasted a while: the nerve cells associated with breathing appeared to relearn their native function.

In another experiment, the light sensitive chemical trigger was placed in the area of the Onuf's nucleus (in the sacral spinal cord, involved in urinary and bowel continence). Again, blue light switched on nerve signals that led to improved bladder control.

Silver described the work last summer at the annual meeting of the American Spinal Injury Association. “It was totally unexpected,” he said. “I was awestruck when function returned.”

Silver told reporters this week this line of work could revolutionize SCI treatment. Such potential is not close at hand, but because it would eliminate surgery or drugs, it’s the most energizing SCI cure news in quite a while.

(Note: Silver was at ASIA to get the Erica Nader award for his long and legendary dedication to SCI cure. The award is named for a Detroit woman paralyzed seven years ago in a car wreck. She was the first U.S. patient to get olfactory ensheathing cells transplanted in Portugal (2003); not getting significant improvement from that experimental procedure Nader now promotes the healing potential of intense exercise, including the founding of an exercise facility in her hometown. Her motto: “Train insane or stay the same.”)

Silver and his team officially released the blue-light studies a few days ago during a SFN poster session and simultaneously published the respiratory success in the Journal of Neuroscience. See Light-Induced Rescue of Breathing after Spinal Cord Injury.

At least two news reports noted this remarkable discovery: the Economist , and the Cleveland Plain Dealer.

Mad

Obama: Change has come to stem cell science

maddogz — Tue, 11 Nov 2008 14:52:00 GMT

Day one of the Barack Obama Administration, a mere ten weeks away, will witness a dramatic shift toward the pro-cures movement in this country. The freshly inaugurated Obama will almost certainly lift restrictions on federally funded embryonic stem cell research.

The president-elect supported the Stem Cell Research Enhancement Act, legislation twice vetoed by President Bush. Here’s then-Senator Obama back in 2007 when the Act last came up for a vote:

Clearly, we are moving backwards in our efforts with these current restrictions. Stymieing embryonic stem cell research is a step in the wrong direction. It closes the door on many Americans awaiting new treatments that could potentially provide a better quality of life, or, perhaps, even save their life.

My hope, and the hope of so many in this country, is to provide our researchers with the means to explore the uses of embryonic stem cells so that we can begin to turn the tide on the devastating diseases affecting our nation and the world.

Bush policy allowed research on only what amounted to 21 stem cell lines available as of August 2001. As Bernard Siegel of the Genetics Policy Institute puts it, “His rationale being that funding on embryonic stem cell lines created after that date would somehow make the government complicit in the future destruction of human life.”

Clearly, Obama and millions of Americans don’t buy the old argument. In Michigan, ballot, Proposition 2 was passed; it will lift the state’s restrictions on embryonic stem cell research.

In Colorado, Proposition 48 was scorched by voters. This proposed constitutional amendment would have redefined a fertilized egg as a person, virtually criminalizing certain areas of research. Over 70 percent of voted against the initiative.

Meantime the International Society for Stem Cell Research (ISSCR) and other major stem cell advocacy groups are stepping up the pressure to make sure Obama does what they all believe he will. “President-Elect Obama can rejuvenate science and research in the U.S.,” ISSCR President Fiona Watt said. “Millions of patients will be looking to him and to the promise of stem cell research.”

ISSCR has made available an open letter outlining the importance of an unfettered stem cell science. Sign on if you want to add your voice.

Mad

Placebo Nation

maddogz — Thu, 30 Oct 2008 03:28:00 GMT

If your doctor gave you something for what ails you and it made you better -- even if it was a fake drug, or placebo -- would you mind? In other words, would it be OK if your doctor lied to you if it was in your best interest?

A fascinating study came out a few days ago about placebos and just how widely used they are in the U.S. About half of doctors in a survey of 1,200 internists and rheumatologists said they regularly give patients placebos or dummy treatments; 95 percent of the time the patient is told the treatment is “a potentially beneficial medicine.”

Most doctors offered more than a sugar pill; 41 percent used pain killers, 38 percent used vitamins and 13 percent used sedatives.

Just wondering….if the other five percent knew they were taking a dummy pill, wouldn’t that undermine the placebo theory, that is, that patient expectation and belief are what power the non-treatment?

Medical ethicists have weighed in on this rampant placebo report, generally uncomfortable with anything less than full transparency. The American Medical Association recommends that doctors use treatments with full knowledge of patients. But if it works, well, maybe this is a case of semantics, not ethics.

And even if it’s a form of sleight of hand, it’s not necessarily fraud and it’s not entirely dishonest. It may be a trick. But in what way is it not a good one?

This makes me wonder about cure treatments people are getting overseas, with some sort of stem cells being transplanted to cure paralysis, motor neuron disease, lyme disease, etc. Is the doctor banking on high expectation and super-motivated, financially committed patients -- and therefore placebo? In the absence of any solid data to support what amounts to a stack of anecdotal and rather modest success stories, placebo is about all we show-me-the evidence types have to grab on to.

The placebo effect is a complex mind-body conundrum. In many ways it is a matter of faith: Does the doctor make you feel hopeful? Is the bedside manner reassuring and empathetic? Maybe success is related to the reduction of stress, which is good for any body. Maybe there is a psycho-physical connection to release healing endorphins.

The placebo effect ought to be more thoroughly studied. Here’s an excerpt from a well-reported 1999 New York Times article by Margaret Talbot called the Placebo Prescription

The truth is that the placebo effect is huge -- anywhere between 35 and 75 percent of patients benefit from taking a dummy pill in studies of new drugs -- so huge, in fact, that it should probably be put to conscious use in clinical practice, even if we do not entirely understand how it works. For centuries, Western medicine consisted of almost nothing but the placebo effect. The patient who got better after a bleeding -- or a dose of fox lung, wood lice, tartar emetic or any of the other charming staples of the 19th-century pharmacopoeia -- got better either in spite of them or because of their symbolic value. Such patients believed in the cure and in the authority of the bewigged gentlemen administering it, and the belief gave them hope and the hope helped make them well.

Talbot goes on:

In an influential article first published in 1955, the Harvard researcher Henry Beecher concluded that between 30 and 40 percent of any treated group would respond to a placebo. But studies since then have shown placebos working for certain conditions -- pain, depression, some heart ailments, gastric ulcers and other stomach complaints -- in closer to 50 or 60 percent of subjects, sometimes more. Indeed, it's not unheard of for placebo effects to exceed those attributed to the active drug.

There’s more:

....evidence that depression is an especially placebo-sensitive condition has only been mounting. The splashiest comes from Irving Kirsch, a psychologist at the University of Connecticut, who contends that the multibillion-dollar success of Prozac and its brethren may be attributed almost entirely to the placebo effect. In a study published this past June, Kirsch and his co-author, Guy Sapirstein of the Westwood Lodge Hospital in Needham, Mass., analyzed 19 clinical trials of antidepressants and concluded that the expectation of improvement, not adjustments in brain chemistry, accounted for 75 percent of the drugs' effectiveness. . . "The critical factor," says Kirsch, "is our beliefs about what's going to happen to us. You don't have to rely on drugs to see profound transformation."

Getting to the point regarding profound transformation of paralysis:
In article than came out this week in the Chicago Tribune about David Martin, a quad who went to Russia for stem cell treatments, the reporter, of course, noted the controversy about unproven treatments in rogue, profit-seeking clinics. Martin got some modest gains. Says the reporter, “If patients feel improvement, experts say, it's likely a placebo effect or the result of their body's own healing mechanisms.”

Placebo effect? Was Martin mislead? Tricked? Scammed? He says he’s a happy customer, out $81,000, but happy. What’s the problem here?

One other current event placebo story: Geeta Shroff was in Australia the other day talking about her controversial embryonic stem cell treatment in India. Once again, it’s placebo time. Herewith is the comment of Alan Mackay-Sim, director of the National Centre for Adult Stem Cell Research at Griffith University, Queensland:

Certainly there are patient testimonials but these are not scientific evidence. Medical history is full of ‘treatments’ for which there are numerous testimonials that are later proven to be quite false. It is hard to emphasize how strong is the placebo effect and the effect of (even unconscious) bias in assessment of outcomes by clinicians and others in clinical treatments. Without casting any aspersions on patients who have received treatments from Geeta Shroff and others, there is a strong pressure (conscious or unconscious) to report positive outcomes for treatments that one has high hopes for, a personal commitment to, and for which one has paid a lot of money.

They may be positive results, but the way that medical treatments are these days validated is to do a proper clinical trials were you can really test whether or not there is an effect.

A lot of treatments have in the past thought to be real treatments have turned out to be placebo effects for example; you know that's where just the belief that someone is getting treated has enough to change their biology in some way.

What’s the point? Placebo is a powerful thing and we don’t know enough about how it works. Maybe science should pay more attention to expectation and hope.

And maybe the clinics whose successes appear related to placebo effects should do more to formally document what’s really going on with their patients. Or else admit they have nothing to sell but belief.

Mad

Stem Cell Trial May Finally Get Go-Ahead

maddogz — Tue, 21 Oct 2008 17:54:00 GMT

The Scientist, a prominent life sciences magazine, reported that the first clinical trial using embryonic stem cells may finally get the green light early in 2009.

The stem cells have emerged from the work of Hans Keirstead, a scientist at the Reeve-Irvine Spinal Cord Research Center at the University of California, Irvine.

Earlier this year the Food and Drug Administration put a hold on a 22,500-page Investigational New Drug application submitted by Geron Corporation, for whom Keirstead developed the oligodendroglial progenitor cells. The cells are derived from embryonic stem cells and injected into the spinal cord injury site seven days after injury. Animal results (published over three years ago) showed significant recovery of the animal's ability to move and bear weight.

The FDA never spelled out its objections but clearly the agency wanted to be sure the treatment is safe. The big fear is that the cells continue to divide and flourish and form a teratoma, or tumor. Immune rejection might also be an issue.

Geron president and CEO Tom Okarma told a New York Stem Cell Foundation conference at Rockefeller University last week that the company has had to "educate" the FDA on all the procedures used to grow, quantify, and characterize its stem cell populations. He dismisses the notion that politics is behind the delay and thinks the FDA did the right thing to hold the trial to understand the science and ensure safety.

Okarma told The Scientist that the FDA is nearing the end of its review process and may allow clinical trials to commence within the next three months. "We've got our arms wrapped around it," he said. "It's been a long education process."

While the first Geron trial will involve acute SCI, the company is believed to be preparing a trial for chronic paralysis, not from trauma but as a result of spinal muscular atrophy. More on this in a future post.

Meanwhile, results from the first-ever FDA approved stem cell trial have yet to be released. Two years ago 9 children with fatal Batten disease got injections of neural stem cells isolated from human fetal brain tissue. The stem cells, injected into the brain, are believed to replace a missing protein that characterizes the disease. Kids who inherit Batten can’t produce enough of an enzyme that processes cellular waste substances; the waste builds up, and eventually the cells can’t function

Children with Batten disease suffer seizures, progressive loss of motor function, vision and mental capacity.

One child, a nine-year-old girl, died a year after getting the stem cell transplant. Stem Cells, Inc, the sponsoring company, says her death was not related to the treatment but was a result of Batten’s symptoms.

In a release, the company stated: “Two independent examinations of the patient's brain, conducted by pathologists at Oregon Health & Science University (OHSU) and Stanford University Medical Center, did not show any abnormal reaction to either the transplantation procedure itself or to the HuCNS-SC [stem] cells that were transplanted into both sides of the brain. Specifically, there was no evidence of tumor formation or abnormal inflammation. The examinations did find atrophy of the brain, as well as diseased neurons containing the toxic cellular waste known as lipofuscin. Both of these pathologic features represent classic manifestations of the underlying disease.”

Promising results were released recently from another Batten disease trial, this one using gene therapy to turn on the production of the missing enzyme. Said Dr. Ronald Crystal, chairman of the Department of Genetic Medicine and chief of the Division of Pulmonary and Critical Care Medicine at New York-Presbyterian Hospital/Weill Cornell Medical Center, "The genes are incorporated within the genetic material of the cells, which are then able to produce a protein that is deficient in Batten disease."

Gene therapy significantly slowed the disease progression in eight of ten children; two died from seizures that were not believed to be related to the treatment.

Stem cells and gene therapy are poised to become revolutionary new tools to fight disease and disability. Let's speed the process and move the best bets to clinical trial, here and now.

Mad

A night by the ocean, a day on the sand

maddogz — Thu, 16 Oct 2008 22:08:00 GMT

Life Rolls On, the LA-based charity started by injured surfer Jesse Billauer, held its annual Night by the Ocean dinner gala last Sunday at the Kodak Theater in Hollywood. It was in the same room as the Oscar’s party. It was billed as black tie, which in New York means the men wear a tux. In Hollywood it means wear a shirt, preferably with a collar. For surfers, it means shoes, although Rob Machado, in flip flops, didn’t get the memo.

This was the fifth annual LRO event, having emerged from more humble roots in a Santa Monica pub. It’s managed to keep a funky, chaotic feel (it is a surfer thing). Last year they took over the Beverly Hills Hotel; it was a cool party that featured Jackson Browne on stage, with Paris Hilton flitting about the room.

This year featured another room full of 500 beautifully coiffed and cleaved people, no paparazzi. It was better planned and timed, though host Sal Masekela (X-Games host on MTV) didn’t make it and had to have his script lipped by people far less comfortable in front of a microphone. Jesse B held court with his posse of ambassadors (sports guys paralyzed in action). The event raised about $340,000, a portion of which supports spinal cord injury research; the Reeve Foundation has received $80,000 from LRO in recent years.

On the same day, up the coast about 150 miles, was another SCI-oriented event, also the fifth annual, an offroad sand dune race to raise money for SCI Research Advancement, a small non-profit based in Solvang, Calif. SCIRA was formed a few years ago by Will Ambler, from Solvang, a paraplegic as a result of a high-speed motorcycle crash. This year the Beach Race at Oceano Dunes brought in about $18,000. That’s exactly how much Paris Hilton bid last year for one day of surfing and hanging out with Jesse Billauer. But we’re all in this together, right? One for all, all for one? You bet, Groucho.

Ambler made a name for himself in 1999 when he threatened to sue a prominent University of California/San Diego scientist, Mark Tuszynski, for withholding human SCI treatments that were developed on animal models paid for by state taxpayers. To be sure, Will is not ready for life to roll on; he’s an aggressive advocate for cure, now, not in the whenever future. Here’s what he told me back in 2002: “The time has passed for making excuses.” He volunteered to be first in line for a treatment with Tuszynski’s methodology, and promised to indemnify all parties if he didn't get better, or if he got worse. “It's time to move forward. Failure, even death, is progress,” he said. “At least we'd know what not to do.”

Ambler to this day maintains that Tuszynski wasn’t honest with him back then, but he dropped the lawsuit, raised private money, about $200,000, hired a neurosurgeon/scientist from Los Angeles, Michel Levesque, and set forth a research protocol to get results and move from animals to humans. His outside-the-system, citizen-science model was set up with a produce-or-perish imperative: no results, no money. A two-year deadline was set in place.

How’d that go? So far, after six years, no results, and almost no more money. I spoke with Ambler the day after the beach dune event. “We started out with Levesque, but that didn’t work out that well.” Due to complications at Cedars-Sinai and some legal issues, Levesque couldn’t do the lab work. “He subbed it out to Jean Peduzzi.” She was then at the University of Alabama/Birmingham and is now a neuroscientist at Wayne State in Michigan.

Peduzzi, a Catholic who has testified in Congress on behalf of pro-life research (e.g. adult only, no embryonic research) has worked with a number of combination cellular treatments for long-term injured rats. Here’s what she’s used (per the SCIRA website): neural stem cells, olfactory stem cells including other mucosal components, olfactory ensheathing cells, umbilical cord blood cells, bone stromal cells, microglia. Along with the cells are substrates for growth (placental derived matrix, small intestine submucosa, fibrin) and various factors to stimulate growth (IGF, inosine, neuronal differentiation media, T3), disrupt scar (ABC chondroitinase) or enhance metabolism (cAMP, rolipram, bone morphogenic protein-7).

Yeah, Ambler knows all about the briar patch of science. All sorts of complications have forced delays. Meanwhile Peduzzi has not published her results on over 300 rats but seems to favor olfactory mucosa transplanted to the spinal cord, similar to what Carlos Lima has been doing in Portugal for several years and 150 patients. Ambler, who says he’s calling the shots, is not fully in agreement with Peduzzi (Lima has a 95 percent failure rate, Ambler says. “To replicate his work is a step backwards.”)

Peduzzi, for her part, is probably going to ride the bench anyway. Dr. Levesque is the blade Ambler wants in the picture for the surgeries, whatever they might be – some type of cell in some form of matrix, with growth factors and a drug of some sort. Ambler says a Kentucky company called RhinoCyte has a cell that might work. Same with a Maryland company called Neuralstem – they also have a cell for SCI repair ready to go once FDA says OK.

What’s next? Ambler is looking for more money, about $3 million to take cellular therapies to Phase I trials. That’s a little heavier lifting than a fancy dinner or sand dune race can handle. “You have to talk to people who have money,” says Ambler.

“I talked to a guy who’s got big money; he says ‘what’s it going to take.’ I tell him three million. ‘Is that it?’ he says.”

Mad

A Tale of Two Pills

maddogz — Thu, 09 Oct 2008 19:39:00 GMT

..it was the best of times, it was the worst, you knew that was coming. I got my copy of the monthly journal Spinal Cord today. This is the house publication of the International Spinal Cord Society and the primary repository of clinical research in SCI. There’s a paper from a team at the Boston VA: "Evaluation of cranberry tablets for the prevention of urinary tract infections in the spinal cord injured patients with neurogenic bladder."
I thought we put this to rest years ago: cranberry works. Dr. Spine says it’s so. Cranberry juice, cranberry raisins or cranberry extract pills help prevent urinary tract infections. Not by making the bladder acidic -- by making it hard for e. coli bacteria to stick to the bladder wall. So 100 years of anecdotal success and a few scientific studies was less than convincing. Turns out the data best supported by fact said that cranberries work for women.
This new study is a randomized, double-blinded, placebo-controlled crossover trial (neither patients nor providers knew who got cranberries or sugar pills; each participant got either cranberry or placebo for six months and then switched to the other).
Cutting to the chase, 47 men completed the study as the cranberry lobby sighs relief. Sixty percent fewer UTIs were recorded among the guys taking cranberry pills. That is a significant result. No reason not to take cranberry extract: it's cheap, it has no side effects.
The other pill in the news is gabapentin, marketed by Pfizer as Neurontin. Many people with SCI have taken this for neuropathic pain, although it is prescribed "off label" for anything but epileptic seizures and postherpetic neuralgia (shingles pain). The off-label use of Neurontin breathed new life into a what was once a minor drug, generating enormous profits for Pfizer. They got slapped with a $430 million fine in 2004 to settle allegations the company overactively promoted off-label use of the drug. Nonetheless, Neurontin's sales rose from 15 percent off-label in 1994 to 94 percent in 2002, according to the U.S. government. The fine really wasn't so hard to swallow: The drug's sales were $2.3 billion in 2002.
(Neurontin is off patent now too, which means gabapentin is a generic drug. Pfizer brought out a new anti-epileptic that is also used off-label for pain. They call it Lyrica. So far, there is no off-label drama with Lyrica, except for severe withdrawal difficulties among people have who are getting off the drug, and that’s another story.)
Here's the news that's putting major heat on Pfizer: the company apparently used spun-up data to boost its sales efforts. Documents filed in a federal court in Boston this week suggest Pfizer postponed publication or altered the conclusion of studies that found no evidence that the drug worked for various off-label uses. Here’s what a senior marketing manager wrote in a rather damning e-mail: “We are not interested at all in having this paper published because it is negative!!” The Boston Globe has the best reporting on this.
What is at stake is a potentially giant class-action lawsuit against the company. Insurance companies want to be paid back money spent on prescriptions for unapproved uses. A Harvard School of Public Health expert estimated that there were 43 million off-label prescriptions written for Neurontin as a result of the company's promotions. That’s a load of payback.
Pfizer argues that it didn’t mean to trick the data and says class-action isn’t the fair way to litigate. They are willing to defend the drug on a case by case basis.

Mad

SCI and the Wars

maddogz — Wed, 08 Oct 2008 14:03:00 GMT

It’s distracting in these times of economic vaporization, but we’re hearing a lot more about the war in Iraq these days, not because we really want to think about more than 4000 Americans who died there, or nearly 100,000 civilian deaths. It’s due to the presidential campaigns and the supposed choice between Obama’s exit plan/white flag of defeat or McCain’s even-if-it-takes 100 years victory with honor. Doonesbury got it just about right: McCain’s need for victory in Iraq allows him to re-fight Vietnam – see, if we can win an open ended war if we stick to it, that would go for ‘Nam too. If we could have won, says the comic book soldier, “then we didn’t really lose, and that’s the same as winning.”

The point is, the war is still going on and men and women are still in harm’s way. We have heard a lot about brain injury in recent months; as many as 20 percent of those who served in Iraq – 320,000 – have acquired some kind of brain dysfunction. Interestingly, the numbers of those coming home with spinal cord injury is rather small – in the range of a few hundred. It’s apparently low because of body armor that didn’t exist in Vietnam, for example, where at least five times as many were paralyzed.

New Mobility magazine takes a look at SCI and the ongoing war: “A New Generation of War Vets Comes Home,” by Alan Rucker. Says Rucker, “We decided to profile a few of the newly-minted SCIs, specifically from the Iraq front, and hear their stories first hand. We reached these vets, some only a few months away from combat, through VA contacts in Florida and Southern California, and through various Paralyzed Veterans of America regional offices.”

It’s a compelling document. Helps you remember that wars are not just about good guys and bad guys. Wars are about people who die, and people whose lives are changed forever.
“A majority of Americans decided a couple of years back that invading Iraq was a bad idea, so they've just tuned it out like last season's Dancing With The Stars,” says Rucker. His article puts the reality of war into proper focus.

Mad

Stem Cell Tourism: Heavy Baggage

maddogz — Mon, 29 Sep 2008 14:15:00 GMT

There was quite a bit of talk about stem cell tourism last week at the World Stem Cell Summit in Madison, Wisc.

For good reason: It’s a fascinating confluence of homegrown medical distrust, internationalism and online culture, with a dash of adventure and blind faith. These medical pilgrims are enchanted by hopes driven by years of media expectation. Many believe that the promise of stem cells has been thwarted not by science, but by politics. It’s the wild west of medicine and there’s no end in sight.

Nobody really knows how big this overseas cure thing is but clearly there are lots of people with disease or disability in a state of suspended judgment. They are going to the other side of the world, spending great sums of money for untested cell treatments they read about on websites set up by the clinics. Nobody knows what’s really going on, where the cells come from, what they do once transplanted. What’s more, in case things don’t work out, there is no legal recourse.

No attempt is made to document results or to track patients over time. It’s here’s-your-dose and adios. Internet testimonials then substitute for scientific publication.

I’ve been following renegade therapies for many years; back in the mid-1980s a handful of Americans went to Russia for some kind of enzyme treatment to make their spinal cords recover. Didn’t work. Remember the fetal shark tissue clinic in Tijuana? I went there and met the doctors, and patients. Nobody got any kind of meaningful recovery that you could remotely say was a result of fish cells. Pretty good scam, especially for being in the pre-Internet era. Anybody remember Neuralyn, the magic juice from Utah that cured paralysis? That one wound up in criminal court and we’re all left to wonder just how easy it is to prey upon the motivated.

Nowadays it’s routine to hear about people going to China or India, or Thailand or Russia for stem cells. It’s interesting that even the stories that take a line against this practice always, in every case, include a testimonial that appears to cancel out all caution. The set up: Desperate parents take out second mortgage to bring child to India for last hope therapy, gets dosed with stem cells, kid gets better, but of course you must remember the whole thing is disreputable and risky and well, you know, maybe the kid would have gotten better anyway, ahem, placebo effect, greedy scam artists, etc etc. The part you remember: The parents say they’d do it again in a heartbeat, and so should you.

There has yet to be a report that singles out people who didn’t get better, or who got worse. And nobody really says it, but stem cell tourism may be a disaster or two away from implosion. If people came back from stem cell Shangri la with cancers or pain syndromes or maybe even dead, you would want to know about it. Not sure you will. But one bad story about stem cells could muck up legitimate research efforts; that’s the fear and the clarion call to action.

Back at the Summit: Reeve Foundation Board Chair Peter Kiernan in his day-one keynote address urged the stakeholders in mainstream stem cell science to consider policing the frontier. As he put it, people are getting some kind of cells “squirted into them” with the only regenerative effect being on the bank account of the snake oil salesman doing the squirting. “I promise you,” says Kiernan, “that if we do not police ourselves, we as a group will be policed.” There remains the sticky issue, he admits, of “who gets to be king.” And what the punishment is.

A panel specifically addressed stem cell tourism on day two. Wise Young, the scientist/physician who runs the online CareCure Community made a couple of very good points. First, he says, let’s admit that the cure seekers are going to go over pretty much no matter what anyone says to them. He’s advised many not to go, he says, but they go. And they will keep going over until there are treatments in their homeland.

Second, says Young, let’s don’t call these medical travelers desperados, that sets them on edge. Nobody wants their motives to be desperate. Let’s instead call them “determined.”

Young’s plea is to educate the patient community to understand the risks and to protect them as much as possible from harm. Kudos to Wise for running the CareCure boards – the single best place anywhere to get information about overseas clinics.

The panel went along as you might expect, caution mixed with reports of modest functional improvement. Graham Creasey, a physician who now heads the SCI unit at the Palo Alto VA, presented some light data on Amanda Boxtel, a Colorado-based paraplegic who wasn’t there in Madison (she told me she’d been invited to the Summit but didn’t want to be the center of controversy, since she has gotten way better after stem cell treatments in India). Creasey said the most important gain for Amanda was probably her sense of hope. Well, who can put a price on hope? It may well be worth four trips to Delhi and $80,000.

The panel was just about to end when a man stood and said stem cells had given his young son his life back. Doctors told him there was no hope. He took the boy to the Dominican Republic for treatment and he got better. “You’re the doctors and scientists,” he said, “but I’m just a dad.”

What part of the session will be remembered? Probably not the part about being cautious.

Click here for a link to a local newspaper report on the session.

Mad

Brains + money, galvanized by passions of advocacy

maddogz — Wed, 24 Sep 2008 21:16:00 GMT

More MadWire from the 2008 Stem Cell Summit in Madison, Wisc., birthplace of embryonic stem cells.

Do not doubt that regenerative medicine is going to revolutionize health care. There was talk in Madison about a fledgling industry at the “tipping point.” To be sure, the stakeholders gathered here validated the depth and breadth of innovation and opportunity, here and abroad. The scientists, the real superstars of stem cells, painted a clear picture of hope. The financial and legal sectors, including government, states and big pharma and even the international reinsurance industry, knows where this is going and they are not about to miss the action. The advocates for the people in need of treatments, they put the heart in the equation and came away feeling the inevitability of progress. It adds up.

The field of stem cell therapeutics has indeed tipped.

New ways to treat disease and trauma will emerge; clinical trials using human embryonic stem cells will occur next year. New models for health care delivery will be worked out, including the development of global banks of stem cells. A pledge will be made to keep social justice in the mix – not only the rich will benefit from new medicine’s bold promise.

Enough on the grandstand.

Highlight for today, wherein Tommy Thompson takes credit for keeping federal money in stem cell research. You remember Tommy, former governor of Wisconsin, former secretary of Health and Human Services for the Bush administration, former candidate for the GOP presidential ticket. He gave a keynote address at the Summit and told a story he said had never been told before.

In August 2001, Bush called Thompson over to the White House for lunch. The president’s man Carl Rove joined them. Bush, in between bites of a peanut butter and jelly sandwich, asked Rove and Thompson to debate embryonic stem cell research. Rove opposed them; Thompson had already been on record in support. “I want to learn about them,” Bush said.

They went back and forth for an hour and a half. Thompson didn’t get specific about Rove’s point of view so let just guess it was righteously fundamental and faith-based. Thompson, with a booming oratorical style that makes the current GOP candidate sound like Don Knotts, intoned thusly:

“Mr. President, you can double the budget of the NIH, or you can give more money to cancer. But do not allow research in embryonic stem cells to end. You will always be remembered as the person who stopped stem cell research. Every American has got someone afflicted by cancer or Parkinson’s disease, or Alzheimer’s. Everyone suffering has some hope in embryonic stem cells. You have got to find a way to allow this research to continue.”

Says Thompson, “I am absolutely certain that if that lunch had not taken place, research in the 78 stem cell lines [ed. note: he means the embryonic stem cell populations that were already in place, even though the actual number that were any good for research was just 21] would not have taken place.” In other words, if Rove had made the call, there would have been an absolute ban on embryonic stem cell research instead of the severely limited amount the president did allow.

Mad

MadTown Hosts Stem Summit

maddogz — Mon, 22 Sep 2008 20:41:00 GMT

Madison, Wisc. – Here’s the message from the 2008 World Stem Cell Summit: The tool kit to repair bodies damaged by disease and trauma is coming along. Great progress is being made, clinical trials are coming, treatments are in the pipeline. The experts gathered here in MadTown, including many of the top people in stem cell science, industry and advocacy, feel the revolution, it's in the air here. But hold on, it’s going to take more money, and more time to make sure cell therapies are safe and reliable.

It’s not just the money that’s got to be managed. The expectations of the public need a reality check too.

Here is a highlight of Monday’s sessions. Peter Kiernan, board chair of the Reeve Foundation, delivered a stirring keynote address, fashioned after David Letterman’s Top Ten format. It’s a call to action. Some of the comments, unless they are in quotes, are MWs.

10. Get politics out of stem cell research. (A familiar refrain from C Reeve when he was advocate number 1).

9. Recruit a new generation of scientists; bring in young investigators to a field they may perceive as risky. “Not the size of the slice, it’s the size of the pie.” (California, getting all the love it deserves from the stem cell nation for its $3 billion stem cell initiative, is indeed poised to bring in 600 to 1,000 new scientists in the next year or two.)

8. Get more money for translational research (that’s the term for moving from the lab to the clinic; in other words, turning science into medicine. There’s a big “valley of death” getting ideas out of the lab and into the complex and expensive clinical trial process. Says Kiernan, “We’re pretty good at picking good ideas – we can pick Secretariat but we can’t get Secretariat down the home stretch.”

7. Think globally. (That’s already happening, evidenced by the collaborative spirit of this meeting and by the impressive research from Japan, by the ambitious Chinese research programs and by first rate work from Europe, Canada and Australia.)

6. Refocus the debate. It’s not about Dolly the sheep or cell replacement. (It’s the promise of doing “amazing things.” Says PK, “Lives are at stake; we’re poised to change the face of the planet.”

5. Educate the press. It’s not about who wins and who loses (as the media are wont to size things up). “The press is very good at condensing complexity,” says PK, “But we need to guide them.”

4. Work with industry; collaborate with business. (California is all over this idea, about to pass out millions in grants to private companies – it’s seen a wise investment.)

3. Encourage international stem cell banking. (Stem cells are indeed a public resource; they must be made available all. There are important social justice issues to deal with, along side ethics and science.)

2. The stem cell community needs to police itself. For one, it needs to protect stem cell tourists from “fraud science” in overseas clinics. “I promise you, if we don’t police ourselves, we as a group will be policed.”

And the number one thing the stem cell community needs, and soon:

We must achieve a clinical breakthrough. (The public supports stem cell research and has shown a willingness to pay for it. But there has to be sustained progress to sustain support. You can't hurry up and wait forever.) That’s all for now, more to come. Mad

Reasonably Accommodated

maddogz — Fri, 19 Sep 2008 17:27:00 GMT

New site, clean slate, fresh ideas. MadWire promises to keep things moving here in blogland. Let the details unfold as we go, starting next week live from Madison, Wisc., site of the 2008 World Stem Cell Summit. Expect news, personality, background and if the words are working, a sense of being there too. Until next time, don't get mad, get wired.

MadWire