New government cash for trachea transplanters Videregen

The trachea-transplanting company Videregen, based in Liverpool, got another £2 million grant from UK governmental agency Innovate UK, to advance their tracheal replacement technology. Videregen are business partners of airway transplant enthusiast Martin Birchall and his UCL, together they saw their Phase 2 clinical trial Tetra terminated by the EU Commission, while the phase 1 trial Inspire, also funded by Innovate UK, was suspended without recruiting a single patient. A related clinical trial with larynx and upper trachea replacement, RegenVox, was also terminated (more here). It was run by Videregen’s partner Cell and Gene Therapy Catapult UK, a giant UK business funded with £85 million of public money, to make Britain a great industry leader in regenerative medicine worldwide. Tracheas and other lab-grown organs are apparently high on the list, the affair of Paolo Macchiarini long forgotten.

With so many setbacks and parliamentary hearings, Videregen almost gave up hope and started to seek new partners to sell decellularised tracheas to, in China and the USA. Yet the suspended phase 1 trachea transplant trial Inspire can theoretically resume, and Innovate UK showed Videregen and Catapult UK a backdoor to that. Right when Inspire funding was aborted in March 2018, Innovate UK gave Videregen another £2 million, to perform this trial, running from November 2018 till October 2021:

Autologous Stem-Cell Based Tissue Engineered Treatment for Bronchopleural Fistula

“A bronchopleural fistula (BPF) is an abnormal hole between the airway (bronchus or trachea) and the chest cavity When a BPF develops, air that is breathed can travel through the abnormal hole and enter the chest cavity, which can result in life threatening infection. BPF is a rare but potentially fatal complication of lung surgery with high death rates. It occurs particularly after removal of a lung for lung cancer or sometimes after lung transplantation. Treatment often requires multiple surgeries, long hospital stays and a major impact on quality of life. Despite improvements in surgical techniques and advances in treatment options, a standardised and reliable treatment option is still lacking.

This project aims to test a new, potentially curative treatment for patients suffering with BPF, through use of a tissue-engineered patch, seeded with the patient’s own stem cells (which are grown from their bone marrow), to seal the hole. If successful, this will allow permanent healing of the fistula and more rapid recovery of the patient.

Studies have shown that tissue scaffolds and stem cells can aid in the healing process, encourage revascularisation reducing the inflammatory response, and so improve regeneration of the tissue. Donated human airway tissue will be processed using Videregen’s proprietary technology to remove cells and cellular remnants. The patient’s own stem cells will then be used to reseed the airway tissue scaffold, a portion of which (a patch) can then be used to close the hole in the airway of the patient.

This project will complete an initial clinical trial in 5 patients to evaluate the safety and initial effectiveness of a tissue-engineered stem cell seeded patch, generating data to support progression to a larger clinical trial to further test the efficacy of the tissue engineered medicinal product. Ultimately, has the potential to provide a curative treatment for patients suffering from this severely debilitating condition and provide support to expand the technology to other serious conditions, where organ replacement options are lacking or in short supply.”

Patients with bronchopleural fistula are very rare and have a very poor prognosis. The hole is usually patched with patient’s own muscle or fat tissue, but Videregen has obviously a better idea: a piece of rotting cadaveric trachea, seeded with what they think are stem cells. The patient only has to forgo established therapy and survive long enough for Videregen to prepare the regenerative magic, which some willing clinicians will stitch in. Puzzlingly, in this case the doctors will be not at UCL but at Royal Papworth Hospital NHS Foundation Trust, in Cambridge, UK. For that, the hospital will be remunerated with £400k. Catapult UK gets £760k, presumably to decellurise and regenerate tracheas in their brand new GMP facility in Stevenage, the rest (over £800k) goes into the pocket of Videregen and its CEO Steve Bloor. With that new money, Bloor will be able to buy lawyers to intimidate half of England, like he tried with the Liverpool academics Patricia Murray and Raphael Lévy (read here). There will be enough money left to clean up Google search of my articles, as someone from the UK already did. The patients namely must never know of what goes on, or they might not agree to be sacrificed for someone’s financial interests.

Videregen’s and Catapult’s friendship with UCL has suffered in recent years. In May 2016, Catapult submitted an application to move the Inspire clinical trial site from UCL Hospital to a private healthcare facility, The London Clinic (see documents, including Patient information sheet and consent form, here):

“We don’t foresee any issues with respect to study special care as we are proposing [Martin Birchall] as PI for The London Clinic who is also the PI for the UCLH site. [Birchall] has practising privileges as a Consultant at the London Clinic.” [he does indeed]

Their new partner is  Royal Papworth NHS Hospital , and the surgeon in charge of the Videregen collaboration there is Aman Coonar, who is described as “Successful life sciences angel investor” with London Business Angels (LBA), in this report from a 2014 Angels meeting organised by Videregen. LBA in turn is presently a listed shareholder of Videregen. Some might think there is a conflict of interest, which could affect the correct reporting of the clinical trial’s results. We can rest assured that Dr Coonar probably only wants to help Videregen save lives with their advanced regmed technology, and can be trusted to relay the outcome of that clinical trial earnestly and honestly. This is also why just in 2018, LBA welcomed Videregen at the Business Fest in July 2018
 

The bronchopleural fistula patch clinical trial has not been yet approved by the UK authorities, as I learned. NHS Health Research Authority is utterly unaware of any standing applications for ethics approvals, never might having issued any; and the medicinal product agency MHRA has also issued no approvals for this clinical trial, which is expected to conclude in less than 2 years. It is however worth remembering that they eagerly approved everything else Videregen and UCL were up to in this regard, and let us not forget who advises (or used to advise) MHRA on technology issues: Martin Birchall.

“Successful” trachea transplants

With this new clinical trial, it doesn’t matter how long a patient will live after the operation: the death will be surely unrelated to the patch, which will be predictably declared a success for stem cell technology. Next step will be, as indicated in the last sentence in the above summary, the revival on Inspire clinical trial, and four tracheal stenosis patients will get a new trachea. In between, there probably will be compassionate use cases, as UCL did in 2017, in the middle of the raging scandal and despite past experience with dead patients. Innovate UK lets it rain for Videregen.
https://twitter.com/LizzieKristina/status/762926956350414852

Inspire funding was originally procured in 2014 from Innovate UK based on a trachea transplant (using Videregen’s patented decellularisation technology) which was performed in London in 2012. This is from grant’s abstract:

“This project seeks to create a niche, highly defensible, innovative regenerative medicine product with a global commercial potential of an estimated minmimum [sic!] £70M annually This is aimed at patients with a life-threatening disease which would otherwise be unattractive had the same team of experts not already tested a clinical prototype which has shown promise to be a one-off cure for severe structural airway disease.”

That “one-off cure” was 15 year old Shauna Davison, my regular readers know about her, more recently the story was covered by The Telegraph. The girl’s mother was talked into agreeing to the transplant, utterly unaware that another cadaveric trachea recipient, Keziah Shorten, died just one month before Shauna was operated by UCL professors at Great Ormond Street Hospital (GOSH). Shauna’s trachea collapsed two weeks after the operation, deprived of oxygen, the girl died of a heart attack. But the business must go on, and post mortem Keziah’s memory (or at least the connection to UCL) was erased, while Shauna was presented as a success story. Dead 3 weeks after the operation from a collapsed trachea, because Shauna was denied a stent, but here she is being paraded as success once again, together with two other other children (Ciaran Lynch, the fate of the third child, operated in 2017, is kept secret by UCL till this day):

“GOSH has already started using similar tissue products in children. GOSH has already done three successful stem-cell trachea transplants. GOSH was the first children’s hospital in the world to do so and remains the only children’s hospital to do this work”

One of Shauna’s surgeons, Paolo De Coppi, now runs his own organ manufacturing line at UCL, and one wonders if he would be willing to come to the GOSH branch at Emirates to field-test the produce. Ethics dumping to paying customers, you know.

Validated technology

The bronchopleural fistula patch technology which Videregen and Catapult UK are so keen to validate on 5 patients, was previously tested under related conditions on pigs, by their close collaborators UCL and Northwick Park Institute for Medical Research (NPIMR, which incidentally is another stakeholder of Videregen). It was the paper Herrmann et al 2017, where Birchall tested his decell-recell lyrynges on an unclear number of unsuspecting pigs, which led to death of several animals and duplication of several images (more here). Incidentally, the related 2016 PhD thesis of Peggy Herrmann (nee Lange) is top secret, UCL categorically refuses any access to it even under Freedom of Information request. In that Herrmann et al 2017 study, 3 x 1.5 cm patches made from donor tracheas (prepared using Videregen’s patented vacuum-assisted decellularisation approach) did not do too well inside pigs’ airways: they mostly detached and disappeared somewhere inside the pig, where even Birchall could not find them.

“The remaining de-cellularised scaffold material could be identified in three animals, laying partly displaced on the exterior surface of the host thyroid cartilage(Fig F-H). The cartilage component of the de-cellularised scaffold remained acellular but occasionally at the peripheral edges cells were observed migrating into the cartilage. Surrounding the scaffold cartilage were discrete areas of clusters or tracts of inflammatory cells”

That adverse experience with airway patches would of course never discourage Videregen, but it should have made Innovate UK stop and think. Unless of course…

What if Videregen’s grant proposal cited the airway patch clinical studies of Heike and Thorsten Walles? My readers will recall this married couple from Germany, consisting of adventurous thoracic surgeon Thorsten and ruthlessly inventive biologist and former member of the German Ethics Council, Heike. The two sued me in court, and I have to tread carefully here as there is a “Threat of Punishment” issued by the court in Würzburg against me for ridiculing Walles and their papers full of manipulated data. Now, the Walleses met and fell in love with regenerative medicine and each other in Hannover, at MHH, in the department of regmed enthusiast Axel Haverich. Incidentally their common boss there was Haverich’s adjunct professor…. Paolo Macchiarini.

Walles tested their airway patches first in 2003 at MHH, on a cancer patient. He lived for 9 more months and died on cancer, while the patch, made from decellularized pig intestine seeded with patient’s own cells, was declared a resounding success of regenerative medicine, even if the peer community did not entirely agree. Macchiarini was the corresponding author on 2 to 3 papers resulting off that patient, but the entire credit goes here legally to Walles. The corresponding authorship was Macchiarini’s reward for (checks court settlement) doing as Walles told him: sticking the patch into the patient, writing the paper and submitting it to journal, because the newly enamoured dream couple Heike and Thorsten were busy with more important things.

Walles then moved to Stuttgart, where two more tracheal patches followed, larger in size, on two patients. These were also resounding successes, as they led to several scientific publications and a popular book celebrating Thorsten Walles as one of brave angels in white who “risk everything” for their patients. Sadly, one patient committed suicide (his previous suicide attempt was what made him Walles’ patient in 2009 in the first place), feeling that the patch brought him no health improvement, while failing to rejoice on Walles’ behalf about their new Würzburg professorships and career success. What that young Indian man never knew of: his predecessor from 2007 suffered total organ failure and bled to death soon after the operation. That cancer patient was namely put by Dr Walles on severe anti-coagulation regime, to stimulate blood circulation inside the patch, which however had to be removed. But as I was educated, the patient was dying of terminal cancer anyway and was hence a perfect research subject for innovative therapies, even if no cure for his main disease or any life extension was expected. All three experiments with trachea patch were done under compassionate use (which by definition forbids research on patients), without any prior animal testing or toxicity studies and, at least those in 2007 and 2009, without any ethics approvals. In the papers Walles published later, deceased patients were presented as alive and well.

I alerted the University of Würzburg, where Heike Walles is professor (her husband moved on to a new position far away in Magdeburg) that Videregen is now using a technology similar to that of Walles. Würzburg was supposed to be investigating Walles together with MHH for two years already, under the pressure from scientific community, but apparently the investigators got bored. Absolutely nothing happened, not a single measly correction explaining the photoshopped data or invented ethics approvals, and now Germans are sleeping through while Videregen and UK take the lead in airway patch regmed engineering!
https://twitter.com/voice_prof/status/609084790734766080

You probably now are trying to get your head around this story. How can a public funding authority like Innovate UK give £2 million to same exact people who bullshitted them before, and for same bullshit? Whose 3 clinical trials were stopped for being too dangerous and lack any scientific foundation? Who bully their critics in academia with lawyers? Maybe these Glassdoor reviews from Innovate UK employees will help:

Update 14.09.2020

Exciting news! After Videregen removed the trachea transplant advertising from their website (backup here), the deaths of Shauna Davison, Keziah Shorten and others were reversed and never have happened. This is why the grant by Innovate UK to Videregen to continue applying that airway replacement technology was extended by another £249,000.

And the bronchopleural fistula clinical trial was green-lighted by in May 2020 MHRA and is listed as ongoing!

Videregen's new website no longer mentions it's trachea transplant ambitions but look at this, archived from just last year:https://t.co/CxIpbCHgSn https://t.co/WrMk02fFTI pic.twitter.com/j2ikrqHvbK

— Patricia Murray (@PMurray_65) September 13, 2020