May 8, 2013

The youngest-ever recipient of an artificial trachea, coated with cells produced from her own body, made history last week as well as headlines around the world. What is the connection between CCSVI and an artificial trachea implant? It’s substantial—and important to you, if you are suffering from MS.

First, a bit of background. Hannah Warren is a 2½-year-old Canadian-South Korean patient, born with a rare congenital condition known as tracheal agenesis (basically, born without a windpipe, or trachea) It’s a lethal condition, unless the patient is continuously ventilated. Hannah’s survival was prolonged by means of a tube inserted into her mouth. Side effects included not being able to take food orally or to speak. Because her condition has required constant medical management since birth, she has been hospitalized in Seoul for her entire life.

Through connections between the Children’s Hospital of Illinois in Peoria and Seoul University Children’s Hospital, a contact was made that suggested something could be done for Hannah through a regenerative medical approach. Over the span of most of Hannah’s life, prolonged negotiations occurred among the two medical institutes, the FDA, the surgeon, various charities, and US government immigration. Through a process that took two years, Hannah was moved to the US, where the surgical team led by Dr. Paolo Macchiarini, of Sweden’s Karolinska Institute, performed a 9½-hour operation during which an artificial trachea, treated with stromal cells obtained from Hannah’s bone marrow, was implanted.

This was not the first time Dr. Macchiarini had performed this procedure. Between 2008 and 2010, Macchiarini successfully transplanted artificial tracheas in eleven adult patients in Europe using adult autologous, bone marrow-derived, stromal cells. During that time the knowledge base for regenerative science increased almost exponentially. In just two years, in vitro cell expansion techniques in the lab reduced timelines for coating a trachea scaffold from nearly two months down to four hours.

Just as with the patients in Sweden, Hanna’s original cell sample came from her own bone marrow, aspirated with a small needle which was inserted into the iliac crest of her hip bone. This process has also advanced to become minimally invasive and painless. From the marrow sample, the appropriate cells were separated, washed, and grown onto the artificial scaffold in a lab environment, where it took a few days for them to multiply to coat the new trachea.

Comparable approaches to regenerative therapies have already been used to propagate urethras and bladders. Cadaver and animal veins have been grafted with autologous cells for human implantation. Cell-coated porcine and bovine valve implants are now being used in heart procedures.

Dr. Richard Pearl, co-surgeon with Macchiarini in Peoria calls it “the page-turning in science, like the first heart transplant or penicillin.” Co-surgeon Dr Mark Holterman said of Hannah, “She was a prisoner who can now have a relatively normal life.”

Dr. Holterman’s reference to being “prisoners in their own bodies” is not lost on MS patients who see obvious similarities between coating an artificial trachea scaffold and a weakened vein scaffold. Many MS patients have been watching the news on Hannah with intense interest. “This is exactly why my veins remain open to this day,” says David Summers of Murfreesboro, Tennessee. David had the combination stem-cell and percutaneous venoplasty procedure done at CCSVI Clinic in mid-2012. “The same stem cells that were taken from my own bone marrow were re-infused into my neck veins at the time of the liberation [Combination] therapy. They immediately coated the inside of the vein and grew new tissue within hours that was the same round shape as the expanded vein. After that, the vein couldn’t return to its old twisted shape because cells grew around the new natural shape in a permanent layer. Baby Hannah has a new airway, and I have new jugular veins, based on the same principle.” (David previously had liberation therapy in 2010 with only temporary benefits. As of this writing, May 2013, David continues to be disease free and has now applied for his previous job as a medical transcriptionist as he continues to recover)

As a PhD biological researcher, and CEO of Regenetek Cellular Technologies, who based the Combination Therapy Protocol (CTP) in part on Macchiarini’s research, I have been following Dr. Paolo Macchiarini’s research for some time now, and have referenced his work in pursuit of protocol objectives for grafting the inner lumen (inside space or cavity) of the vein as a surface scaffold.

From Macchiarini’s hypothesis, and other well-known studies, I further theorized that the same source of cells he’s using to coat implants would bind mesenchymal stromal cells (MSCs) to a scaffold by way of chemotactic interaction with a cell surface. This means that they will work even better once deposited in a clinical dose in the place in the body needing repair because these unique cells are attracted to areas of injury and inflammation. In each so-called liberation therapy, the deposition of cells would serve to fabricate a more stress-resistant vessel that maintains its structural integrity and new shape (by way of balloon expansion), and therefore long-term patency. This basically allows the patient to have a new vein using the old one as a scaffold, without the need for stents.

This is a potential page-turner for liberation therapy—another missing piece of the puzzle. Knowing this, I’m not sure it’s ever going to be appropriate to perform venoplasty without this additional support intervention, if it is known that in virtually all cases, if left alone, the ballooned veins return to their anomalous shape within hours, days, weeks, or at most, a few months. The stem cell treatment must occur at the time of the venoplasty while the veins are expanded; because the veins are pro-inflammatory at that time, this naturally attracts the stem cells.

Dr. Saroj Shekhawat, Chief Science Officer at StemGenic Therapeutics, and a graduate of the prestigious Weizmann Institute in Rehovot, Israel, agrees my hypothesis would be correct. “The veins that were just open[ed] by the balloon would act as a scaffold because they are in a pro-inflammatory state, and the stromal cells introduced to the area would naturally be attracted to the expression of certain proteins. In fact, it would be no different than what Dr. Macchiarini does with his tracheal coating except that it is done in vivo [inside the body]. This seems like a very good solution for the continuing problem of strengthening thin-walled vessels like veins, which would also become fibrous and deteriorate with each venoplasty. So doing venoplasties over and over is quite dangerous to the patient. That should be avoided and patients should know the risks.”

Dr Shekhawat continues, “Our research has shown that when these MSCs are injected through blocked blood vessels, they are sort of like magic bullets that go on to repair plaque-afflicted areas, thereby restoring the blood flow, which results in better availability of oxygen and nutrients to the myelin and existing neuronal population. The activity of stem cells is not restricted to only myelin formation but does include repairing blood vessels to ensure continuous flow of nutrients and to sustain oxygen to the neurons.”

Beyond keeping the neck veins open, it is important to treat the areas of the central nervous system (CNS) that have been insulted and injured by the demyelinating disease process. The key here would be to turn the disease off and repair the tissue damage that’s been done. Secondary considerations would be to avoid additional interventions.

With a year of experience behind us in developing and testing new protocols, we have now had the opportunity to analyze Doppler Ultrasound studies of neck veins in MS patients prospectively, and those that were stenosed at the time of the therapy continue to remain open after stem-cell treatment. I’m confident in saying at this point that it’s generally longer than they would have maintained patency without stem cells, and—if the veins of these study patients continue to maintain long-term patency—that proof of efficacy for venoplasty as a therapeutic strategy for MS might stand the scrutiny of a trial.

An article for the CCSVI Clinic’s website describes the early outcomes of the first 16 patients studied. The main feature of this investigation is that overall, patients improved by a total of 47%, according to an aggregate of the three scales (appropriate to MS) used over an average period of 155 days, post therapies, and the average EDSS score dropped from 6.0 to 3.5. Significantly, one patient dropped from 9.5 to 6.5. None of the patients feel that they have had an attack of their disease since their treatment, confirming clinical findings by Shi , Connick and Brazzini. There has been no need to suggest a second intervention for any of the patients at this time. There were no serious, minor or unintended adverse events identified and no deaths have occurred for any other reason since the beginning of the study period. Patients will continue to be followed for a period of 5 years.