For those who understand spanish (Dr. Vaquero)

[GRAMMY]

GRAMMY, I have the feeling that this question has been discussed before but I forget, if so
But what is the reason that it's so long between the completion date on a site such as listed on clinicaltrials.gov and the date in which the publication is actually available for all to see... Like I always used to look at the completion date listed on the clinicaltrials website and think: "ok, that is the approx date that we will hear news or results of such trial", but then I always end up feeling like a gullible doe-eyed sucker because the end date listed almost never correlates to getting information on the the said trial

Things you need to click on and read at the trial site to follow along are some important "historical changes" and what is the Primary Outcome (which is most important) and then read through the Secondary Outcome to see what they hope to have tested on their subjects. They really did ramp up the amount of data they wanted to gather and publish on their patients. From baseline to final follow up is 24 months for all arms of the trial.

With this Ph 2 trial, they posted it with a start date of 7-2015 without a known patient number and an estimated completion of 5-2017.

Then they show the trial next started October 7th, 2015 with a patient number of 10.

It is considered Day 1 for each patient the first day of the first cell administration. The remaining 2 doses will be administered at intervals of 3 months from the first administration (of the treatment period after, months 4 and 7). At the end of the study will be performed a full assessment of the variables collected along the study trial. The expanded cells are administered in the subarachnoid space by lumbar puncture. The minimum duration of the follow-up period for each patient is 10 months after the first administration.

On November 12th, 2015 they've settled in on a more definitive primary outcome goal and they are added to the trial.

On June 13th, 2016 they change the status from recruiting to active (not recruiting) and enrollment from anticipated to actual.

On September 6, 2016 they added the secondary arm of investigation to the trial in addition to saying the trial results would be submitted to the Spanish authorities and they will publish in a scientific journal.

On August 27th, 2017 the regulating authority was moved from the Spanish Agency of Medicine to the FDA drug and device and potential export status. Data will be submitted to the CTD of Spain. Anonymized individual data of participants will be shared with Authorities at the end of the Clinical development plan by the CTD (Common Technical Document). Results will be published in a scientific publication. Time Frame: Starting at CTD submission to authorities.

Depending upon the journals publication time frame and required edits from the publisher, it can add to the time frame when it actually comes out to the public. I personally believe the time to be around 6 months for many journals but that can vary quite widely for various reasons and the journals a study is submitted to. For instance, Phase 1 ending to journal appearance was 17 months. (Even that time frame isn't terribly unusual.)

[Pauly1]

Repair of injury site: bundled demyelinated nerves causing crosstalk (expressed as hypersensitivity)

Dr. Vaquero had up to 14 dermatomes sensory recovery. Average was 6.8.

Before/after MRI shows myelomalacia and gliosis disappearing, being replaced by solid tissue. So if there are intact nerves I'd gather the altered sensation would be due to crosstalk from becoming bundled together and demyelinated. The MSC injections appears to repair this. Though his current work is at the thoracic level so we have no cervical results to look at.

We believe that it is similar to what has been described when our paraplegic minipigs received intralesional administration of cell therapy. In our experimental model, after MRI and histological studies, we described that functional recovery was associated to the filling of centromedullary cavities by transplanted cells, together with the presence of new fascicles of myelinated axons extending longitudinally at considerable distance from the area of lesion.

At least in 7 patients (patients 01, 03, 04, 06, 08, 15 and 16) MR myelography showed, 12 months after surgery, a reduction of hyperintensity of, supposedly cystic or gliotic intramedullary lesions, even with disappearance of lesions that in the surgery we identified as a mixture of microcysts, gliosis and myelomalacia.

This is MSC stem cell injections done along the injury site as patient 15 had:





full paper at https://www.celltherapyjournal.org/c...48145/mmc1.pdf


This sort of treatment started in 2005. It is now 2018 and not available for western SCI community

In 2005, Gerry Allen (C5-C6) had umbilical cord stem cell injections at & below his injury by Beike (China), also with recovery of sensation.

More details.


We are now in 2018.. 13 years later. What is the delay getting this to folks that need it?

[KIM]

https://www.celltherapyjournal.org/a...510-3/fulltext

[Pauly1]

Dr. Vaquero has another paper where they are doing lumbar puncture MSC treatment:

Repeated subarachnoid administrations of autologous mesenchymal stromal cells supported in autologous plasma improve quality of life in patients suffering incomplete spinal cord injury

The article has Video S1 - Improvement in walking after cell therapy.

Impressive improvement. This treatment delivery being the same as done by Cell Medicine (Panama) or Beike (Thailand/China).

[Pauly1]

Hot off the press by Dr. Vaquero:

Intrathecal administration of autologous mesenchymal stromal cells for spinal cord injury: Safety and efficacy of the 100/3 guideline

This study supports previous evidence showing that patients with SCI can improve their neurological dysfunction after intrathecal cell therapy with autologous MSCs. In the absence of data about the best treatment guidelines, our present experience is that intrathecal administration of MSCs with a dose of 100 million cells every 3 months, up to a total of 300 million (100/3 guideline), is safe and shows benefit in patients with SCI.

[Silvio GS]

So now just bring it on

[Pauly1]

Silvio GS, Dr Vaquero replied to my query for C3-C4 SCI treatment below. There is way more demand than supply here.

Dear Sir: Your lesion corresponds to an area of injury to cervical level with gliosis

- This can be treated with our cell therapy medicament without the need for direct surgery (only intrathecal stromal cell administration supported in autologous plasma ) - You can not expect great improvements, but you could achieve recovery from sensitivity, spasticity, neuropathic pain and improvement in sphincter control.

The problem is that this treatment can only currently be done in our hospital, at no cost to patients and we can only take care of patients from the Spanish social security system. We can only treat a maximum of 60-80 patients / year and at this time we have more than 400 patients waiting for treatment.

Sincerely,

J Vaquero

[Mize]

bummer.

[Mize]

Repair of injury site: bundled demyelinated nerves causing crosstalk (expressed as hypersensitivity)

Dr. Vaquero had up to 14 dermatomes sensory recovery. Average was 6.8.

Before/after MRI shows myelomalacia and gliosis disappearing, being replaced by solid tissue. So if there are intact nerves I'd gather the altered sensation would be due to crosstalk from becoming bundled together and demyelinated. The MSC injections appears to repair this. Though his current work is at the thoracic level so we have no cervical results to look at.





This is MSC stem cell injections done along the injury site as patient 15 had:





full paper at https://www.celltherapyjournal.org/c...48145/mmc1.pdf


This sort of treatment started in 2005. It is now 2018 and not available for western SCI community

In 2005, Gerry Allen (C5-C6) had umbilical cord stem cell injections at & below his injury by Beike (China), also with recovery of sensation.

More details.


We are now in 2018.. 13 years later. What is the delay getting this to folks that need it?

What is the D-level ??

[GRAMMY]

In 2005, Gerry Allen (C5-C6) had umbilical cord stem cell injections at & below his injury by Beike (China), also with recovery of sensation.

We are now in 2018.. 13 years later. What is the delay getting this to folks that need it?

Here's what Wise Young had posted about "Beike". If you do a search, there is tons of information posted about it.

Jon,

I am sorry that it seems to be pouring down all of a sudden. However, I think that it has been pent-up and a long time in coming. I have generally refrained from commenting critically on the Beike claims to date in hopes that Beike would publish some of their results. The problem is not what Beike does not claim. It is what they (and through you) are claiming, i.e. that they have a therapy that is improving recovery in 80% of people with spinal cord injury, that is 100% safe, and that people would benefit from repeated therapies. You suggest that anecdotal data is acceptable. Please, as a person who has been in a medical familiy, you know what the problem is with anecdotal data and the reason why they are not accepted in the medical world. You know that what you are doing is wrong for the following reasons.

Anecdotal data are usually incomplete and therefore misleading. We don't know the denominator. Only the good cases are being presented. It doesn't seem that your web site is presenting any of the bad cases that don't turn out. You claim here that 80% of the people say that they have gotten improvements that they are satisfied with. What is the denominator? Where do you get this data... Are you repeating what you are verbally told by the doctors at Beike? When are people reporting their satisfaction, when they are being discharged, when they are told that the recovery will still take months to happen, and that they should expect recovery after they get home? Have there been any systematic effort to contact the patients and find out if they are actually recovering and finding out whether any of the people are having complications?

There is a strong placebo effect in situations such as these. Add to that a strong desire and expectation for recovery, you will see many people reporting positive effects of the therapy. This is true of any treatment, including ones that should have no effects whatsoever. Let me give you an example. About a decade ago, a couple named Vigil (Berverly and Tom) charged many people with spinal cord injury to treat them with a product called Neuralyn (Source). They advertised their product on the web and they had many testimonials from people who swore that this ointment cured them. In fact, we had several of these people here on spinewire and cando (the precursors to CareCure). People were told (like you are telling them that the treatment is 80% effective) that Neuralyn was 85-95 percent effective. They were told that Tom Vigil is a doctor with training in biochemistry, that the work is supported by a distinguished board of physicians and scientists, and that the cost of research and patent applications justified the $300-$500 charge per vial of the ointment. This couple has been convicted of criminal fraud.

How is what Beike doing any different from what the Vigils did? The fact that Beike has not and is not following up on their patients is not reassuring. The fact that they don't seem to be doing standardized neurological examinations and publishing their results is bothersome. The fact that they are making claims of safety and efficacy, directly or indirectly through you, your web site, or anecdotal claims from patients, without publishing the results in respected medical journals suggest strongly that the data cannot and will not pass peer-review. Finally, the fact that they are charging for unproven therapies, even asking patients to come back and pay for repeated therapies is unethical. I have indicated my skepticism that the therapy by the Beike group would be effective for the following reasons.

1. Non-HLA matched cells. The Beike group is using non-HLA matched cord blood cells to treat patients. Two decades of experience with cord blood transplants strongly suggest that HLA-matching is essential for engraftment of cord blood cells, particularly cells that are being given peripherally. For the Beike group to claim, with no data whatsoever that the expanded cells are not being rejected and are engrafting in the spinal cord, is not acceptable. The cells (particularly those that are injected intravascularly) are very likely to be rejected in most of the patients.
2. Cell expansion and purification. The Beike group claims to be expanding the cells and purifying CD34+ cells for transplantation. Are they really doing this? What is the purity of the cells? Is the procedure GMP? Are the cells being grown in the presence of bovine serum? How are they ensuring that the cells are sterile and not contaminanted? Have the procedures been approved by any regulatory agency? Is there any evidence that the cells are surviving or are getting into the spinal cord? Incidentally, I know of no group that is consistently able to row and expand CD34+ cells. I would imagine that if the Beike group actually has a method that works, they would be crowing this from the roof-tops and publishing it in the best journals, and getting a lot of funding from venture capitalists.
3. The lack of publications is concerning. Where are the publications, even in Chinese? I spend a lot of time in China and I have yet to talk to any doctor who thinks that this treatment has beneficial effects in spinal cord injury. The fact that Beike are setting up operations to so many cities is worrisome. It seems that no part of what they are doing has been subjected to peer- or regulatory review. While you claim that the procedures are safe, where is the data? The data should not be based on whether or not Cherry or whoever has personally talked to anybody who has had a problem with the procedure. It is the responsibility of the doctors who are carrying out the study to document adverse events. The problem is that I don't think that Beike is doing a study. It is just a business concern with a serious conflict of interest because the treatment is earning a great deal of money.

At the beginning, I was willing to adopt a wait-and-see attitude, hoping that they would come out with some publication, to provide some evidence of what they are doing and to support their claims. But, I just don't see any of this happening. I am seeing more anecdotal evidence being presented on your web site, the citation of unsubstantiated statistics such as 80% improvement of the patients, and continued unjustified scientific claims being made with no evidence to support the claims. I therefore cannot recommend that anybody goes to this group for treatment. It has all the hallmarks of a scam.

Wise.