Friday, March 13, 2009

Geron ‘Claytons’ ESC trial – scientists and smart money smell a rat

You could not have missed the news that at last, embryo stem cells are to be given to humans! Surely this is the vindication of all the snake-oil about ESCs being used to treat humans?

Wrong, of course. As we explained in our Media Release in January, the Geron trial does not let an ESC within a mile of any patient's spine – that would be to invite disaster in the form of tumour formation. Being very patient, we reminded journalists again of the true shape of stem cell 'therapy':

"Journalists and the public need to be told the truth – not sneaky suggestions that 'embryonic stem cells' are being given to patients at last!! They are not. Repeat: they are not. They never have been and never can be put into humans, because embryonic stem cells form tumours in animals. Only adult stem cells can be put into humans – and have been used now successfully in thousands of patients."

In fact, we explained this as far back as October last year when Professor Alan Trounson was using the planned Geron trial to salvage some vestige of relevance for ESC research. In our October 27th Media Release 'Phoney Breakthrough with Embryonic Stem Cells' we said:

"There is only one way, paradoxically, for embryonic stem cell trials to proceed and that is for researchers to find a way to ensure that absolutely no embryonic stem cells (ESCs) are used in the trial!

"ESCs themselves are dangerous, since they form tumours called teratomas, and in the scientific literature ESCs are referred to as 'rogue cells' or 'unwanted differentiating types'. The task of Geron Corp and others is to 'terminally differentiate' all ESCs into other, mature cells – a bunch of nerves, perhaps, or heart muscle cells – but above all, no ESCs please!

"This is not a stem cell transplant, this is not ESC therapy – it is just transplanting a bunch of mature cells, with no capacity to regenerate themselves. This is not a 'revolution' in regenerative medicine; it is scientific sleight of hand.

Geron's is a Clayton's ESC trial: the ESC trial you have when you are not having an ESC trial, etc… Yet it will do for journos and pollies eager to justify the increasingly redundant field of ESC research.

However, it appears it is not good enough for smart private money and some sensible stem cell scientists.

Read here only this week in the investment journal about the investors' suspicions:

"Wall Street's health care investors, most notably biotech-focused hedge funds, have been more inclined to steer clear of Geron or short the company's stock.

The reason?

"Conference calls for Wall Street health care investors with experts critical of Geron's research, like those held by Summer Street Research on Monday, explain why.

And what said the expert on the conference call? He said the same as we have always said: that the "white-rat-walking" videos (whether Geron's or the famous Gearhart video used so misleadingly by Prof Trounson with our MPs back in 2003) are highly dubious when extrapolated to human spine injury of treatment; that the transplanted nerve cells (not ESCs) are 'foreign' (extracted from a deceased human embryo) and therefore the patients need immune suppression; and that even if Geron did publish 22,000 pages of research to get its experiment permitted, that will not stop some of these cells possibly reverting to the dreaded ESC and forming a tumour. That, says the specialists, would be a disaster.

Here is the central part of his reported comments:

The doctor on the Summer Street conference call, a spinal cord injury expert who has also conducted stem cell research, was skeptical about Geron's study because there is very little animal data to support the theory that a therapy derived from stem cells will benefit patients with severe spinal cord injury.

"The fact that Geron's entire study hinges on this one experiment in eight moderately injured rats is tenuous in terms of efficacy," he said.

The experiment referred to, conducted by Dr. Hans Keirstead of the University of California at Irvine, was done on eight rats whose spinal cords were purposefully injured to paralyze the hind legs. Rats treated with the Geron therapy after seven days saw some function return to their paralyzed legs. Geron commonly shows a video of the rats before and after treatment as part of the company's pitch to investors.

The doctor warned, however, that the rats in the experiment only had moderate spinal cord injury, while human patients in Geron's first safety study will have severe spinal cord injury. Moreover, when the same rat experiment was conducted in rats with severe spinal injuries or when the start of treatment was delayed for more than a week, the Geron therapy had no effect.

The Geron therapy is derived from a universal donor stem cell line that will be considered foreign by patients. As a result, patients will need to be placed on drugs that suppress their immune systems to lower the risk that the Geron therapy is rejected.

"We don't know what will happen when these cells are placed into a human, which is the reason immune suppression is required," said the doctor on the Summer Street conference call. "The risk is that these are not patients you would otherwise want to have on immune suppressants because the severity of their spinal cord injuries, the trauma they've suffered, their surgery and wounds make them more susceptible to infection."

Moreover, the doctor said, patients' bodies may reject the Geron therapy as soon as immune suppression drugs are stopped after 42 days, per the study's protocol. Typically, when a patient undergoes some type of transplant, immune suppression therapy is required for life.

Another safety concern is the risk that the cells in Geron's therapy may grow uncontrollably and form tumors on the spinal cord. Geron has stated that tumor growth has not been detected in any of its animal studies, but again, the theoretical risk remains when Geron moves its therapy into humans.

"If one patient gets a tumor from the Geron therapy, it will be catastrophic," said the doctor on the Summer Street call.

Why, given the drawbacks of immune suppression and tumour risk, and a dodgy animal basis for doing the experiment in the first place, would the FDA approve this trial?

And why, in all the science journalistic coverage of this alleged new frontier of spinal 'treatment', did they not even acknowledge that we have already done this trial using adult stem cells? They can't say they weren't told, as we gave them chapter and verse in the January MR. Our comment then remains our judgement on the Geron trial (and associated market and media hype):

We already have a published article in the Journal of Spinal Cord Medicine ( using an adult stem cell preparation in human spinal cord injury, with no harm to the patients, and early signs of recovery of sensation. We also have over 2000 patients treated with direct adult stem cell transplant for heart disease, with exciting results, and thousands of other patients treated for dozens of medical conditions – including diabetes – all published in the medical journals. There has never been a single human treated using embryonic stem cells – and even this Geron experiment is a hoax, as it does not inject embryonic stem cells at all.

This Blog will watch the Geron experiment closely; and we give unsolicited financial advice that you would do well not to sell all to buy GERN.