The Carmel Turner Story Gaining Access to Treatment in Australia The Greek Study Videos Overseas Treatment Options and Trials Contact Me & Other HSCT'ers in Forum Discussions In The Media
Carmel Turner Adult Stem Cell Treatment for Multiple Sclerosis
Carmel Turner MS stem cell treatment -
The Beam Protocol Step by Step
  MSRA 2011 Funded Research.
Current Recovery
The Carmel Turner Story

 

Hello all

Hi I am Carmel Turner.

First of all, Tina Stahmer is currently fund raising to get HSCT treatment for Ms.

Tina Stahmer

Tina is from NSW, Australia. Australia has currently stopped access to HSCT treatment for Ms. There is a resumption date but delays in access to treatment impact the success of the treatment. Tina  has applied and been accepted for HSCT treatment for MS in India with Dr Amit. We congratulate her community, that have rallied around her to assist her with fund raising efforts.

Tina has still not achieved her fund raising goal. As we are personally involved with Tina and Andy we wish to bring attention to their fight.

Her treatment will occur early in December 2012. Tina's disease/disability is aggressively progressing and HSCT will Halt her progression of Ms.

Donations 

‘Something for Tina’ Bendigo Bank (Australia) BSB: 633 000 Acc: 146 882 576, or visit her website 

http://tinasten.wix.com/pleasehelptina#!contact/c21dx

Media : Newspaper Clippings

http://www.merimbulanewsonline.com.au/story/402904/tinas-fight-for-life/

 

 

 

 

Tina has been a very active member of the FaceBook group, HSCT for MS http://www.msstemcell.com/forum.php.

 

The FB forum is the best way to contact Tina and myself and others that have had this same HSCT treatment. 

 

New sections

 

 

 

I have added the following section research.

MS Cause, significant research progress

Explaining how this breakthrough and treatment is as important to 80 plus diseases of the autoimmune system. I am contacted regularly by patients of other autoimmune disease and asked if this site could be applicable to them...and in short... Yes it is!

 

 

 

 

I have included a scan copy of my latest MRI (in my recovery section below) showing that my lesions are shrinking. 

In my media section I have included my latest articles.

I have also added a Youtube video of a presentation from the US HALT study in my scientific evidence sections below. 

 

 

I Like to change the video on my Main page on a regular basis. The following is of Amy Paterson who has obtained HSCT Treatment in Russia

Please donate to her appeal at the following blog

http://amygoesninja.wordpress.com/

 

 

  <iframe width="853" height="750" src="http://www.youtube.com/embed/vxhD_V6Jvnk?rel=0&autoplay=1" frameborder="0" allowfullscreen></iframe>

 

 

Please click here to visit my new fund raising section.

Click to download as a printable word document.

LAST UPDATE :

1.International treatment options page and added fund raising page on the 28/07/2011 17:00 PM. India 40k, Israel 75k, Germany 78k.

This website is still a work in progress.

********************************

Hi I am Carmel Turner.

I am one of the few lucky MS people to receive Autologous HSCT (Autologous Hematopoietic Stem Cell Transplantation) treatment for Multiple Sclerosis. I received this treatment over a 3 month period, September - November 2010 in Canberra, Australia.

 

I was diagnosed in 2009 after the birth of my daughter in 2008. In total, it took nearly 10 months to be diagnosed after noticing significant gait in my walk since my child’s birth. By the time I was diagnosed I had an extremely aggressive form of RRMS with progressive disability or at the initial stages of secondary progressive MS. I was having a relapse every 3 months. In 18 months I went from a normal able individual, to a person that could not take three steps without holding onto a four wheeler walker that I used at home. When my child was learning to walk I was losing my ability to walk. When I went out in public I was in a wheelchair.

 

When I truly understood how quickly I was progressing and what were the limited approved treatments and their limited capacity to alter the disease progression particularly once the disease became progressive. I knew that I would need to search for upcoming treatments. I did not just rely on my neurologist to supply me with information. I researched every possible avenue for treatment of the disease and its symptoms. I would then discuss them with everyone including my neurologist.

 

My primary source of information was http://clinicaltrials.gov/ and sages medical journal. I went to the search portal on the clinical trials web site above and typed the disease MS, located a registered trial on a particular treatment and located the published review of the trial in the listed medical journals.

 

At the time my father in law had a friend that was being treated for leukaemia. Due to this I knew of the acronym for HSCT and the basic concept that the treatment destroyed the immunity system and rebuilt it from new.

 

Eventually through this activity, I came across DR burt’s work that lead myself to ask my neurologists about HSCT treatment for MS. My neurologist informed myself that the treatment was intrusive and held very little benefit. He said he had been to Germany to observe the treatment, I later discovered he had been to the X-cell center in Germany that does not do the treatment that I was referring to. I then found Dr Burt’s website with all the contact information and patient selection criteria. At the time I was preparing to contact Dr Burt, I saw a news flash about a young man in Canberra called Ben Leahy having the treatment that I was considering at the time. The news flash gave just enough details so I could track down the treating neurologist in Canberra Australia. I sent my patient history and MRI’s to the doctors and I was later approved to receive treatment in 2010.

 

 

Results of treatment have simply been beyond words.

  • I no longer take any MS medication. Only HRT oestrogen.
  • MRI's have confirmed disease activity has stopped.
  • My Disease is in remission (I say remission not cure, BIG difference)
  • When compared to a 18 month old MRI. My current MRI has fewer lesions and no new lesions have appeared since treatment.
  • My appetite is normal again.
  • My EDSS score went from 6.5 - 7.0 down to 4.0 -4.5 so I am no longer wheel chair dependent and walk without aids.
  • My Incontinence has gone.
  • My MS Bladder is gone (where you sit on the toilet for 2 hours waiting while at the same time busting for a pee)
  • My Pain has gone. No more crying myself to sleep.
  • I am Driving again.
  • My cognitive abilities and memory have gone back to normal.
  • My strength in my upper and lower limbs are improving.
  • My Intolerance to heat has disappeared
  • My quality of life has improved beyond words.
  • I am living life and enjoying being a mother to my child again.

 

I have set up this website to empower Ms suffers (and also 80 other autoimmunity disorders) and their loved ones with difficult to locate information. Here is all the information that I have discovered by my research relating to the treatment that I received for Multiple Sclerosis. This is mostly to help those,  like myself, who do not have 5 years spare to wait for the currently running US FDA trails to come to completion and the treatment to be FDA Approved treatment for MS.

 

I had progressed to an EDSS score of 7.0 in two years, death has a score of EDSS 10. When I did not have time to spare I encountered several road blocks to gaining access to credible information on treatments under clinical trials and also a lack of understanding about the different types of stem cell treatments by support resources that MS patients traditionally turned to. I hope resources located on this web site reduces those road blocks for others and provides them with a real alternatives that they may not have been previously aware of.  

 

To date around the world, there have been up to 600 people with MS that has received autologous HSCT treatment under controlled studies. Those studies have shown up to 86% of the patients with MS responding to treatment by achieving complete remission in their MS disease for periods greater than a decade. The treatment resulted in halting all activity of the MS disease in patients that previously experienced regular relapses. Those who responded to treatment, have also had some reversal of neurological damage and physical disability caused by the previously active MS disease. On average, disability improvement is between 1.0 and 3.0 in their EDDS score over a three year period after treatment.

 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2817032/
 

Even more exciting than the success rate of those treated in these trials achieving remission, is the fact that patients with the worst prognosis that have been shown to be unresponsive to approved therapies are the patients that respond best to treatment. In fact most of the trial data is based off patients that fit into this category of MS. The patients that were in the 5 per cent with the so-called malignant and aggressive form of MS, the patients that needed a wheelchair within five years of diagnosis.

 

http://au.news.yahoo.com/thewest/lifestyle/a/-/lifestyle/13351322/stemcell-hope-for-multiple-sclerosis/


The fact that there is only 600 treated in the infers that this treatment is a new discovery. Which could not be further from the truth. The only thing new or cutting edge is giving this treatment to MS patients. HSCT treatment is not cutting edge nor a new discovery. The HSCT treatment that is used to treat MS, is an established and proven treatment that is currently used in hospitals around the world as a standard procedure to treat 15 different diseases including leukaemia. The procedure was invented by a French oncologist in 1959 on five workers whose own marrow had been damaged by irradiation caused by nuclear accident at research facility in Yugoslavia.

 

The procedure was first successfully done in a western hospital in 1968. Since then the treatment has been revised as new technology emerged within the medical field and new practices adopted. This has had a significant impact on treatment related fatalities. On average 50,000 HSCT treatments are performed each year, every year, around the world treating the 15 approved disease for the treatment.
 

The links below are of the general history of HSCT for all diseases. The fatality rates relate to all diseases except for MS as it yet approved.

 

http://en.wikipedia.org/wiki/Hematopoietic_stem_cell_transplantation


http://www.e-mjm.org/2009/v64n1/Haematopoietic_Stem_Cell_Transplantation.pdf

If I had a different disease, a disease that HSCT is approved for, I could have this treatment, 15 minutes down the road from where I live, payed by my health insurance. As a standard treatment for those diseases.

 

Unfortunately even though this is a proven and established treatment for 15 disease, the trials for this particular treatment for MS patients are still occurring. The phase I trials started in 1996, those trials have now progressed to the last double blind phase III trial that is required before this treatment will be covered automatically under US Health insurance. This will probably take another 5 year period for the trials come to an end and another 5 years before the treatment to be used regularly by US neurologist at a time that their patients have progressed enough to justify such a treatment. These trials specifically compare Tysabri treatment effectiveness over an extended period time to slow MS activity to HSCT treatment results of halting all disease activity.
 

 

In America, the HSCT treatment I received is currently progressing through two separate FDA trials using two different types of HSCT treatment. The trials are in Seattle (HALT trial) or in Chicago(MIST trial). The trials started in the early 1990’s and have completed both Phase I and Phase II FDA trials.

 

Seattle HALT

http://www.halt-ms.org/

 

Chicago MIST

http://www.stemcell-immunotherapy.com/

 

The trials use slightly different versions of HSCT treatment. Seattle HALT trial uses a myeloablative chemotherapy protocol while the MIST Chicago trial uses a non-myeloablative (or lymphoablative) chemotherapy protocol. Both achieve the same end result of rebooting the immunity system but through changing the chemotherapy the treatments reboot the immunity system in a different manner. The non-myeloablative protocol is less toxic and less aggressive. A simple analogy using the PC reboot of the two approaches would be that myeloablative switches off the power to the HDD,CPU and memory concurrently and them switches them back on. While with the non-myeloablative shuts the system down sequentially by powering off the HDD and when turning the power back onto the HDD, turning the CPU off and etc. Through this method one part of the system is powered on during the reboot. Both methods achieve the reboot but through different approaches and one is slightly less aggressive in its approach but achieves the same end result.

 

After 16 years since its beginning, the Chicago MIST Trial has started the final phase of trials, a double blind Phase III US Government FDA trial's which will see this treatment covered under US health insurance in five years for people with MS. Once this occurs, the treatment I received will become available to US neurologist as an US FDA approved treatment. This will hopefully result in Australian Neurologist's acknowledging the white elephant in the room.

 

http://clinicaltrials.gov/ct2/show/NCT00273364?term=burt+and+multiple+sclerosis&rank=2

From an article of an earlier form of HSCT, HYCY that is also called Revimmune, HYCY is similar to the current methods used by Dr Burt in his current Phase III trial. The first time they started to use this type of HSCT treatment to attempt to treat auto-immunity disease was in 1977 and the Dr's involved at the time had started to form some idea that HSCT could treat MS and 80 different immunity diseases back in 1977, that are still today considered as untreatable.

http://www.hopkinsmedicine.org/hmn/w08/feature1.cfm

 

http://www.youtube.com/watch?v=SuJj52twOdo

 

As you will learn from further below there are several different types of stem cell treatments. The stem cell treatment I had is very different type of stem cell treatment to the type of stem cell therapy that is on offer through one day surgery centers that operate as stem cell clinics in Germany, China and Panama that use unproven MSC stem cell therapy.

 

The treatment I received involved collecting stem cells from my own body. This is then followed by a large dose of chemotherapy to destroy the bone marrow and clean out each component of the entire immunity system including killing all the T-Cells in the body. The Immunity system is then rebuilt. This occurs by infusing the previously collected stem cells and regrowing new bone marrow. This new bone marrow slowly starts producing new t-cells that does not have the MS disease. The entire process from beginning to end effectively reboots your immunity system. Effectively restoring the patients immunity system back to a point in time, of auto immune self tolerance, the period of time in the patients life prior to MS being active. For a detailed description of my entire procedure please click on the left hand panel or here, BEAM step by step.

 

I have filmed my whole procedure and placed it on You Tube. I have direct links to the videos on the link at the top of this page. These videos show the whole treatment from beginning to end. I did this so others can see first hand what the treatment was like. It is an intense treatment and should only be done after a considered choice.

 

Another reason for the video's was to show that the chemotherapy is the majority of the treatment. It is the underlying reason for remission of MS in Autologous HSCT treatment that took myself 12 weeks to receive. This will hopefully show people what the one day stem cell clinic's in Germany (X-Cell Center), Panama, Argentina and China do not perform during MSC therapy that involves collecting the stem cells and re-infusing them on the same day without any additional therapy. MSC therapy and HSCT treatments are significantly different treatments that achieve significantly different outcomes. MSC therapy is also new treatment and a new form of stem cell treatment that has not completed phase I trials. HSCT treatment is an established treatment in modern medicine used for cancer patients and has been under trial for MS treatment since 1996.  MSC therapy requires multiple treatments at $30,000 a session for results yet to be confirmed by phase II trials while HSCT treatment is a once off treatment that requires no further treatment for established results for two separate US FDA phase II studies.

 

The treatment that I had is a very specific type of stem cell treatment that involves chemotherapy that requires to be an in patient of a hospital. No clinic has the facilities or the know how to perform HSCT which is in effect a Bone Marrow Transplant and needs BMT facilities. HSCT treatment only occurs in state run hospitals that has in patient care facilities capable of caring for a person when they are anaemic.

 

The treatment result of HSCT has been shown to be repeatable in halting all MS disease activity and halt the progression of the disease in its tracks. The only aim of the treatment is to halt all MS disease activity.  The absence of disease activity creates a the respite that the body needs for disability improvement that is on average, an improvement of the EDSS score of the patient between 1.0 – 3.0 EDSS points over a three year period. The stem cells in the treatment do not contribute at all to disability improvement or repair nerves as stem cell clinics would like to infer. The only role that the stem cell’s play in the HSCT procedure is to grow a new bone marrow that produce t-cells that no longer attack the myelin sheath. The treatment is in effect a Bone Marrow Transplant (BMT).

 

Trials so far indicate remission periods greater than 10 years in patients who’s disease was so aggressive that they have been documented by multiple neurologist as to not to respond to any known treatment, who also previous to HSCT treatment, experienced multiple relapses a year resulting in sever physical and cognitive disability in a very short period of time.

 

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2817032/

 

US Gov FDA Safety Phase I Trials for HSCT treatment of MS began in 1995 and successfully completed and US Gov FDA curative effectiveness Phase II started in 2000 that saw the treatment changed by lessons learnt from the phase 1 trials by removing TBI therapy from the treatment that was found to undermine the long term curative result of the treatment it also added significant risk to treatment, when TBI was in use the average fatality rate was 10-15%, after TBI has been removed the treatment the average fatality rate at treatment centers for HSCT reduced down to less then 1% (0.8 at one of Europe’s largest cancer treatment hospitals, Germany Heidelberg University hospital that treats 200 patients a year using HSCT and is one hospital offering this treatment to people with MS).

 

US FDA Phase I and II trials

 

The last phase of trial process of the USA FDA have began in 2012, this trial is the last that needs to occur before your local US neurologist can offer HSCT treatment to later stages of RRMS as an alternative to Tysabri or for SPMS, an alternative to Novantrone® (mitoxantrone) to their patients.

 

Current US FDA Goverment double blind Phase III trials

 

This is the last trial that needs to occur for the HSCT treatment for MS can be covered by US health insurance. The US Gov FDA Phase III double blind comparative study to current treatments (Tysabri) is the last trial that needs to occur before the general MS population has access to the treatment that has been shown to be the only treatment that is capable of modifying the disease course and reversing existing physical and neurological damage.

 

When current US trials come to a conclusion over the next 5 years, and when the treatment is released in the US that results in remission periods of over a decade for 86% of those treated in the US, it will be short period of time before the general release and usage of HSCT by Australian neurologist. I cannot imagine a situation were only US citizens have access to the only known treatment for MS to show such success in effective treatment for patients that were previously considered to be untreatable. 


Economic benefits to the community of treated MS patients are realized through the discontinuation of lifelong immumodulator drugs after treatment. These immumodulator drugs are very expensive and at minimum cost 12 k a year. One of the drugs, Tysabri, cost 35k a year to the PBS scheme, creating a demonstrable saving of 350k in medical prescription cost over a 10 years period after treatment. Most experience substantial reversal of their pre-existing symptoms, something that cannot currently be repeated with current therapeutic approaches.
 

Current selection criteria, targets a narrow window in the progression of the disease cycle. There is a limited time when this form of treatment can be considered. You may be in that narrow window today. In 5-10 years time when this treatment will be released, you may no longer be in that window. I had a very aggressive form of MS that resulted in myself becoming wheel chair bound (EDSS score 6.5 progressing to 7.0) within 2 years of diagnoses. I cannot emphasis enough how close I was being told "sorry, if you came to us sooner". In a very short period of time after diagnoses, I almost became to far progressed within the disease cycle to be considered for HSCT treatment. The longer and more ingrained the damage is the less likely that HSCT will reverse the condition. Trials target those at the end of RRMS and at the beginning of SPMS. Those that have multiple relapses in a year. To qualify for trials you need to demonstrate that you have tried and are unresponsive to all currently approved FDA treatments including tysabri.

If I relied on traditional sources of information about treatment options I would have not been aware of this treatment option let alone the exclusion criteria that I almost failed.

I hope to steer those away from stem cell treatments that give false hope.  If a person Google's "MS stem cell" you will be presented with false hope via advertising for stem cell china, x-cell treatment center, holly hubber south American stem cell clinics, colostrum products. All of these presented options are money down the drain and are scams. Some of these corporations have started to setup charities that present information about stem cell treatments then tell you that their products are apart of the selection criteria. Or simply having their products on the same page informing readers about legitimate research along with products infers some sort of creditability to their products. One of these charity that are nothing more than a marketing front for scam treatments is;

 

http://www.adultstemcellfoundation.org/ 

  

Media

My latest Article in the UK magazine MSRC (Multiple Sclerosis Research Center).

Page 3 of my latest Article in the UK magazine MSRC (Multiple Sclerosis Research Center).

 

To see my current recovery please click on Current Recovery in the Left hand panel.

 

I am contacted by people around the world seeking treatment and others that have already received treatment. I am also in contact with people who are currently or about to start treatment. Through this little community, I have learned how people are gaining access to treatment here in Australia and around the world. I have also meet people that have had the treatment a decade ago here in Australia and also in the US. Both of whom have not relapsed since treatment.

 

You can contact me at  carmelbturner@gmail.com or find me on the face book group HSCT for MS.

 

http://www.facebook.com/#!/groups/149103351840242/

 

 

There are legitimate treatment options overseas to gain access to AHSCT for MS (Including the US, China, Israel and Germany). The legitimate treatment centres are all in public hospitals oncology departments that usually treat cancer patients. NOT private stem cell clinics. Some of these legitimate sources of treatment are currently running USA FDA phase III trials or are treating international patients. Click here to go to International treatment options and trials.

 

I had my treatment here in Australia. It was covered and payed for by Australian Medicare that is limited to Australian citizens. For details of that please click on the link at the top or here gaining access to treatment in Australia.  

 

The scientific Evidence of HSCT for MS

This treatment has been established by nearly a 100 independent studies around the world repeating the same results. Up to 600 people have now been treated in separate trials around the world with an average success rate of 86%. I have links below to the largest studies of registered peered review studies.

 

 

Autologous hematopoietic cell transplantation for multiple sclerosis: a systematic review

 

The long-term effect of AHSCT on MRI measures of MS evolution: a five-year follow-up study

 

JAMAstem_cell_for_non_malignancies.pdf

 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2817032/

 

The Last trial before general release of HSCT treatment in the US is underway. A FDA Phase III double blind study.

http://clinicaltrials.gov/ct2/show/NCT00273364?term=burt+and+multiple+sclerosis&rank=2

 

And here is Dr Richard Burt official web site of his treatment

 

http://www.stemcell-immunotherapy.com/

 

If you would like further scientific material please refer to George Goss scientific reference library for neurologist and patients. George has spent a considerable amount of time cataloguing all peered review scientific journals on this subject and quite simply is second to none.

 

George Goss HSCT Research Reference Library for Neurologist's and Patients

http://themscure.blogspot.com/2010/06/stem-cell-transplantation-reference.html

  

Progress of HSCT treatment.

Since starting this web site a year ago. There has been a huge amount of activity around HSCT for MS. I continue to work with people trying to obtain treatment here in Australia and overseas. This consumes at least 2-4 hours of my time every day. I have been involved in peoples fund raising efforts to gain access to treatment overseas. I have done public talks at rotary events. Explained the treatment and how they can get involved.

 

MS Society Australia growing Support of HSCT for MS that is showing promising results

The HSCT trials in Perth that started after Dr Andrews in the ACT treated Ben Leahy. This trial is being run by Dr Bill Carroll, the chief scientific advisor to the MSRA and treating neurologist. The MSRA also announced a $500,000 grant to establish a registrar of all people that have received HSCT for Multiple Sclerosis in Australia.

 

 

 

 

 

The MS Australian (MSA) Society has this year (2011) re-printed an article from 2008 about HSCT showing promising results for MS. For those that missed it, the link is below.

 

http://www.ms.asn.au/publications/Network Winter 2011.pdf
 

The article does not explain how to gain access to treatment or any mention of the success so far here in Australia. There is no mention of Dr Colin Andrews treatment success of 100% of treated patients. Also, no mention of Dr Bill Carroll and the trials in Perth and their success rate. Both trials are 100% funded by Medicare and the article infers otherwise. At Least though MSA acknowledge the benefit from this treatment. They are starting to educate people of its existence and fund some research through a registrar of those that have received the treatment. This is a huge step forward from the Australian MS society previous position. I congratulate the Australian MS Society in progressing down the path of helping those that they represent by informing them of a treatment existence. This policy change of MSA is now reflective of those MS societies in the US and Europe where one of their members have this treatment, they acknowledge and publish the fact. They also publish in their magazine/website and where to locate their blogs of their experience. This enables those with MS in those countries to be educated about this treatment. 

 

 

The brain center in Melbourne presented a lecture about myself and the other three (Ben,Che,Michael) that were treated in Canberra. The
lecture held for 250 neurologist/neuroscientist specifically about
HSCT treatment for MS at Canberra hospital. The brain center in Melbourne have in total 600 neurologist/neuroscientist, with 50 support personal
at the Royal Melbourne hospital and another 50 admin staff. It is the largest brian
research center in the southern hemisphere. This is the facilities that
is connected to the royal Melbourne hospital which did the 2001
study into HSCT for ms, the first trial in Australia. .



http://www.heraldsun.com.au/news/more-news/melbourne-brain-centre-opens-in-parkville/story-fn7x8me2-1226169015577


http://www.florey.edu.au/about-florey/about-us/melbourne-brain-centre


http://www.florey.edu.au/news-events/in-the-news


http://www.premier.vic.gov.au/images/stories/documents/mediareleases/2011/111017_Baillieu_-_Melbourne_Brain_Centre_Parkville_enhances_Victorias_reputation_for_outstanding_medical_research.pdf

 

 

The MSRA held a public forum on HSCT treatment for MS. The panel included Prof Trevor Kilpatrick of the previously mentioned Florey Neuroscience Institute.

 

Date: Saturday 29th October 2011
Time: 9.30 am – 12 noon
Venue: Jasper Hotel, 489 Elizabeth Street, Melbourne

 Program:

Time Topic Speaker
9:30am Registration  
10am Welcome Mr Jeremy Wright
MS Research Australia
10:10am MS Research Overview Dr Lisa Melton
MS Research Australia
10:30am Stem Cell Therapy for MS Prof Gianvito Martino
Universita Vita-Salute San Raffaele, Milan, Italy
11am MS Repair and Regeneration Prof Trevor Kilpatrick
Florey Neuroscience Institutes
11:30am Living well with MS John Mathews
MS Community Nurse
11:50am Q & A Jeremy Wright

 

 

http://www.msra.org.au/public-lecture

 

 

ENGLAND: Current treatment of Stella

I have a new friend in the UK called Stella and her husband Marc. Stella is currently going through treatment and is detailing her experience in a blog on the MSRC web site and national magazine.

 

 

Norway/Sweden has started treatment of a lady named Hanna Vesterager that had to hire a lawyer and fight for her right for treatment. Hanna has setup an appeal and has a Blog of her current treatment.

 

Hanna has been released from hospital and is now back at home. I have yet to talk to her but it appears she had minimal complications. It is still early days and she is only just starting to recover from a very intense treatment. The MS society in Norway has links to Hanna's blog so those that they represent are educated about this procedure.  The MS Society of Norway even contributed to her personal appeal and encourage others to do so.

 

http://translate.google.com/translate?sl=no&tl=en&js=n&prev=_t&hl=en&ie=UTF-8&layout=2&eotf=1&u=http%3A%2F%2Fhannastamceller.blogg.no%2F

 

http://translate.google.com/translate?sl=no&tl=en&js=n&prev=_t&hl=en&ie=UTF-8&layout=2&eotf=1&u=http%3A%2F%2Fwww.ms.no%2Fhaugaland

 

 

MS Research significant Progress

The most exciting progress in HSCT that has occurred this year. Research has proven beyond all doubt, that Multiple Sclerosis root cause is genetic.
 

http://www.nature.com/nature/journal/v476/n7359/full/nature10251.html
 

The head researchers main hope with this research would above all, destroy hysteria around treatments that a lot of people are making a lot of money, from selling false hope to the most vulnerable.

 

http://www.theglobeandmail.com/life/health/new-health/health-news/massive-study-disputes-zamboni-theory-of-multiple-sclerosis/article2125784/
 


This research proves that MS root cause is a genetic disorder. Environmental factors effect the genetic floor that later triggers a Immunity disease called Multiple Sclerosis. That Immunity disease MS, is then further effected by environmental factors. These factors impact the speed on the rate of acceleration, on the progression through the disease cycle. The MS disease Cycle begin with benign MS, then progress to RRMS followed by RRMS with progressive disability and then SPMS . Diet exercise, Vitamin D, Epstein-Barr virus are external environmental factors that may impact the progression of the disease but their use or management will not reverse or manage this aggressive disease.

 

As a treatment, no amount of Vitamin D tablets will go to the extent of halting the progression of the disease and reversing neurological damage but can have a small effect on regularity of exacerbations and progression in early part of the disease cycle. Modern medicine has a greater ability to manage the disease and no medical profession would recommend relying on vitamin D alone, unless you are determined to prove your ideology of choice and prepared to take responsibility for the inevitable outcome.  Once the disease has progressed to RRMS with progressive disability of an Edss score of greater than 4.0 these external factors management have little impact beyond that of a placebo. Also modern medicine has lost control to the disease and is fighting to regain control that has proven to be rarely regained with current medications.

The research also indicates that those with these genetic markers are more receptive to subtle changes in environmental factors, such as vitamin D. So if two sisters/brothers growing up in the same house, with the same diet and the same location in the world, they will result in two different out comes. As the genetic disorder present in only one of them effects that persons ability to absorb Vitamin D at lower sunlight levels. Two of the 57 genetic markers effect Vitamin D absorption. 

Due to the identification of the genes, scientists will also be able to more clearly define those environmental factors as with the 2 of the 57 genetic markers involve vitamin D absorption. Ms people will not necessary have all 57 genetic markers, which in turn will identify what environmental factor could be the trigger for that individual. They also believe that there are more genes to be found. This science has not been completed but beyond doubt, a large step has been made. It was only four years ago when they only had identified two genes common in MS'ers, so one can see how quickly this science is being established.

 

A great analogy of this research is, genetics loads the gun and a  single or multiple random environmental factors pulls the trigger that creates a disease of the immunity system called MS.

 

This research also explains why those with MS are more likely than an average person to have multiple autoimmune disease.

 

This research also indicates that more than 80 disease are also treatable with Autologous HSCT treatment that would result in a remission in the disease and an Allogenic HSCT treatment will result in a life long cure of the disease. This research indicates that if certain combination of environment factors exist along with certain genes of the 57 genes (not everyone will have all 57 genes), will result in a disease such as Diabetes type 1 Lupus or another combination environment factors trigger with certain genes will result in Autoimmune Gastritis.

 

If I had one of these diseases I would be contacting the same Dr's in Australia and also the treatment centres listed on my international option pages. The only other option is to wait for the 20 years for this research to conclude if you believe that you will not progress further into the disease cycle that may prevent these treatment's from being effective.

 

Diabetes type 1 (Lupus), is one of the trials that Dr Burt is trialling in a Phase II study with HSCT treatment. Dr's previously understood that 80 autoimmune diseases are interrelated, these perceptions were based through general observations of the similar behaviour and similar treatments between the diseases. Now scientist and Dr's have solid science to explain why these diseases are interrelated along with a reason why patents with one autoimmune disease is more likely than others to have multiple autoimmune diseases.

 

Phase I and Phase II study of Type 1 Diabetes Lupus with HSCT treatment.

http://www.nature.com/bmt/journal/v31/n7/full/1703868a.html

 

Dr Burt is also conducting research with the following diseases using similar HSCT treatments to address each disease. If your disease is not listed does not mean that it is not treatable with HSCT, Dr Burt has targeted those diseases that get the most attention.

Rheumatoid Arthritis; Bullous Pemphigus; Chronic Inflammatory Demyelinating Polyneuropathy; Crohn's Disease; Myasthenia Gravis; Peripheral Vascular Disease; Polymyositis; Scleroderma; Sjogren's Syndrome; Vascular Biology

 

Also a link to Professor Graeme Stewart radio interviews explaining these concepts, who is one of an eleven-person team leading this global study of twenty-seven-thousand people across fifteen countries that resulted in these breakthroughs.

 

http://mpegmedia.abc.net.au/rn/podcast/2011/08/bst_20110811_0635.mp3

 

http://mpegmedia.abc.net.au/classic/podcast/current/audioonly/mti_20110815.mp3

 

Graeme Stewart contact details

http://www.radioaustralia.net.au/innovations/stories/s3302315.htm

 

In the interviews not only are autoimmune disease's that root cause is genetic but also HIV infection, that also after infection has a genetic component. Articles that relate to this is below.
 

http://germanherald.com/news/Germany_in_Focus/2010-12-16/506/Man_%60cured%60of_aids

 

Peered review study of the only case of HIV being cured.

http://www.ncbi.nlm.nih.gov/pubmed/21148083

 

Technical explanation of the gene involved in HIV AIDS

http://en.wikipedia.org/wiki/CCR5

 

If I had one of these diseases I would be contacting the same Dr's in Australia and also the treatment centres listed on my international option pages. The only other option is to wait for the 20 years for this research to conclude.

 

 

Future possible Developments of this research

The MS genes discovery are significant not just for MS. Since MS is a disease of the immunity system it relates significantly to other immunity diseases. Type 1 diabetes, Lupus, thyroiditis are all about to hear of progress with their diseases. Scientist researching these disease, now know what to go look for as their disease symptoms and mechanics are similar to MS.

 

Hopefully the first thing we see in our GP office as a result of this established science, is a blood test for MS. Those who test positive will not necessarily develop the MS immunity disease but will give them advanced warning that they are highly prone to developing the disorder. It would also be a huge piece of mind to love ones of those diagnosed with MS. Does my child or my sister have MS, would be answered before the disease disorder and the damage is detectable in MRI scans. There are already blood tests being developed that not only detect MS but what stage of the disease cycle the patient is at and predict disability increase.

 

http://www.msra.org.au/new-blood-test-monitor-damage-ms

 

This research brings us closer to a cure than ever before. We are now able to test if a person has an underlying genetic floor that eventually results in the immunity disease MS turning onto its host. This will enable quicker diagnoses but also confirm who should be a chosen as genetic compatible donor for future Allogenic HSCT transplants which I go into detail further below.

 

 

Autologous Hematopoietic Stem Cell Transplant (Autologous HSCT)

The treatment that I received Autologous Hematopoietic Stem Cell Transplantation (Autologous HSCT) is the closest treatment to a cure that is available in Australia or overseas with an acceptable risk. The risk is a 1% fatality rate. The treatment involves collecting stem cells from the patients own body before a large does of chemo is given to the patient, to destroy that patients immunity system. The immunity system is rebooted by regrowing the bone marrow, the heart of the immunity system from the previously collected stem cells.

The result of this treatment is the patients immunity system becoming antigen naive. Antigen naive means, all the memory of the immunity system that it has gained over your entire life since birth, such as chicken pox that you gained at the age of 5, is removed from your immunity memory. All the memory of your immunity system is wiped and started again from scratch. This also removes the memory of MS from your immunity system. At one stage in your life, your immunity system decided that your myelin sheath was a foreign body that needed to be destroyed. Your immunity system is restored to the state it was, when you were a new born baby, before you had MS.

This form of treatment places the MS disease in the patient into remission. It does result in a small change in the underlying genetic code, but is unlikely to remove all of the 57 elements of the genetic code of the MS genetic disorder. The treatment according to research will result in the remission of the disease for 10, 15 years or a life long change. There is a chance of relapse due to the genetic code that caused the disease in the first place is still present.

Even though this treatment is not a cure, it is the only treatment that has been proven through separate unrelated trials to place the disease into remission. The result of these trials prove that remission is a repeatable event for the vast majority that receive treatment. Due to placing the disease into remission, the body has the opportunity to repair the neurological damage caused by having the disease. I strongly recommend others to consider Autologous HSCT, as it is the only treatment that is proven to place the disease into remission with an acceptable risk. Since treatment I have gone from a wheel chair to walking and starting to lead a normal life. Alleluia.  

 

It has been proven time and time again through several small peered review registered trials to halt all progression and activity of the disease. It gives the human body the reprieve from the disease it requires, to repair the damage the disease has done. Currently large scale FDA Phase III double blind studies are currently occurring. That will see this treatment covered under US health insurance.

http://clinicaltrials.gov/ct2/show/NCT00273364?term=burt+and+multiple+sclerosis&rank=2

 

Progression may occur again due to the genetic floor still being present. If relapse does occur, due to the Immunity system being reset back to a point in time, of at first of being in a self tolerate state of the MS disease (benign MS), then to the beginning of the cycle of early relapsing remitting MS. Patients are in a far better position than before therapy. This is due to conventional therapy has better established record of responding to these phases of the disease cycle.

The patient that had previously progressed in the disease cycle and have deteriorated despite treatment. That patient will be more likely to respond to conventional therapy after a relapse that occurred after HSCT treatment. As a result of the HSCT treatment the immunity system has been restored back to a point in time, to a state of having the upper hand on the disease. Patients that previously had aggressive and unmanageable diseases would be more likely to be, no longer be beyond help.  

 

I have recently located a presentation that was made by the US HALT study in Seattle. The US Halt study is an official phase II FDA trial with the exact same treatment that I received. It is a executive summary of their observations of the Phase II trial and their own conclusions of what the results indicate. They cover both positive and negative results. It also speculates on future direction of treatment once more data collaborates current assumptions and also when other treatments obtain an acceptable risk. Which i go into further in the below section Allogenic HSCT treatment.

 

 

 

 

Allogenic Hematopoietic Stem Cell Transplant (Allogenic HSCT)

 

Another treatment Allogenic Hematopoietic Stem Cell Transplantation will result in changing the underlying genetic code as well as remove the memory of MS from your immunity system.

Allogenic HSCT is a similar operation to Autologous HSCT. The immune system is rebooted. Firstly by destroying your immunity system through chemo therapy. Then your immune system is "rebooted" by growing a new bone marrow through stem cells.

The main difference is who they harvest stem cells from. This treatment harvest stem cells from a genetically compatible donor and those stem cells are used to grow the new bone marrow in the recipient patient. Due to recent breakthroughs of identifying genetic markers of MS the genetic compatible donors can now be screened to ensure they do not re-introduce the disease.

This treatment differs to mine as my Autologous HSCT, harvest's the stem cells from the patient themselves. This treatment, has a significant risk associated with it and that is the only reason why I would not recommend this treatment for MS. The death rate is between 10%-30%.

Problem's occurs after the bone marrow has been created. The new immunity system can identify, the new recipient patients body as a foreign body and starts to attack it. This scenario is refereed to as graft vs host disease (GVHD). This is the primary reason why this form of treatment has a fatality rate of 30%.

If the patient does not develop GVHD or it is successfully treated, they then need to take anti-rejection drugs for 2-3 years. This is to ensure their body does not reject the bone marrow, that is effectively another persons bone marrow. After 2-3 years, the genes from the donor and the genes of the patient effectively blend into a third person. This removes the need to continue the anti-rejection drugs. This state of becoming effectively a third person at a genetic level by having two peoples genetic code blended into a new person, is referred to as mixed chimerism.

This would result in a significant large change in the underlying genetic code of the patient that would have a high likely hood (not guaranteed but highly likely considering the scope of change to the genetic code) removing the underlying genetic floor that caused the disease. This will occur along side with removing the MS disease from the immunity disease as in my treatment.

The immunity system would be cleaned out and rebooted with the newly grown bone marrow. This would remove the MS disease (the faulty anti-gen immunity memory of MS) from the immunity system. Also, the underlying genetic code that created the faulty immunity system in the first place, it would be the most likely cure the MS disease. It will achieve the same as my treatment but remove the possibility of relapse as the root cause has been removed. Even though I believe that this form of treatment is the cure for MS I would not recommend people perusing to cure their MS with this form of treatment due to 1 in 3 patients die.

There is research as we speak that promise to change things. There is a new method of this treatment that takes stem cells from the donor and patient. These collections are mixed before placing them back into the patient. This new form of treatment promises to reduced the death rate down to 1 in a 100 similar to the treatment that I have. Until this is proven through trials with a greater population of 3 patients, I would not recommend this form of treatment. I do though recommend people keep track of it as it holds so much promise. The good news is since I had a Autologous HSCT treatment I have the time to wait for science while living life MS free.

 

 

University of Louisville Phase I/II Clinical Trial - Donor Stem Cell Transplantation (with variable mixed chimerism [mixing both donor and recipient stem cells together prior to engraftment]) for the Treatment of Multiple Sclerosis. Phase III trials are planned for 2014
 

 

http://www.clinicaltrials.gov/ct2/show/NCT00497952

The bottom line is "they" know what the cure for MS is, they are just refining the method of delivery so it is safe for the general population of MS'ers. Now that they know what 57 genes to test for, they can prove it.

As an interesting side note "they" also beginning to understand what the cure for HIV AIDS is, it is the same treatment that will cure MS. The Cure for HIV was discovered the same way as the cure for MS was discovered. A patient with HIV also succumbed to leukaemia, one of the 15 diseases approved for AHSCT treatment. Unfortunately for HIV sufferers there is only one case of a HIV infected patient receiving treatment and all current conclusions and selection criteria is based off this isolated individual. The history of the development of HSCT for MS shows that as more individuals are treated, there is greater amount of data to draw conclusions from and as a result, future patient selection changes. There is no follow up study planned. Instead this case is dismissed in favour of a pharmaceutical managed therapy, just as it is for MS sufferers.

HIV sufferers are at the beginning of the 30 years of medical bureaucracy that has prevented the development of the cure for MS. Like MS sufferers, HIV positive patients only hope to gaining access to treatment within the current orthodox medical practice, is to contract leukaemia or one of the other 14 diseases approved to have access to AHSCT. HIV sufferers are at the beginning of arguing those down that know what is best for them, by denying them treatment under the same argument used to deny MS sufferers treatment, the treatment is too intense while ignoring how intense the disease itself is and the lack of quality of life that results from that disease.

The treatment that Timothy Ray Brown (also referred to as the "Berlin Patient") received was an allogenic HSCT operation, where the donor was proven to be naturally resistant to HIV.

 

 

http://germanherald.com/news/Germany_in_Focus/2010-12-16/506/Man_%60cured%60of_aids

 

Peered review study of the only case of HIV being cured.

http://www.ncbi.nlm.nih.gov/pubmed/21148083

 

Technical explanation of the gene involved in HIV AIDS

http://en.wikipedia.org/wiki/CCR5

 

 

 

 

 

Mesenchymal Stem Cell Trials (MSC)

 

The UK have announced trials into Mesenchymal Stem Cell (MSC) therapies. This type of stem cell procedure is very different than those mentioned above. They have been used by stem cell clinics around the world as they require little skill and are a one day procedure that does not require the patient to be booked into hospital.

As a consequence they have little costs for the operator and can be very profitable. The results of these therapies can be easily misconstrued into something they are not. As a result I have been very sceptical and reluctant to present any information around these therapies. I have been quite frankly disgusted by people promoting MSC as a cure. They are telling people that MSC therapy can cure them of MS and it's symptoms. I hope one day there are legal consequences. The manner that these private operators (such as the X-Cell center) and people like Holly Huber that support MSC as a cure, are simply dishonest. They are saying anything that can mislead a person to secure another dollar. They have set back this type of legitime treatment by selling it as something it is not...a cure for MS or a treatment that can reverse MS.

MSC therapy does not attempt to treat the underlying disease. It does not attempt to halt the activity or progression of the disease. It attempts to repair the damaged done by the disease. It attempts to rebuild nerve damage and to some degree start remyelination of the nerves. The therapy results in improvement in EDSS scores, that can be used to infer by unscrupulous operators that they have reversed MS and MSC therapy is an effective treatment of MS.

However, the slick marketing of these institutions fail to point out that as soon as the patient experience an MS exacerbation / relapse, those improvements are short lived. Depending on the individual's stage of the disease cycle, attacks could occur at 5 years intervals or as in my case before I had autologous HSCT treatment every 6-12 weeks. So this therapy, does result in EDSS improvement until your next attack, which as in Holly Huber case, invites you back to spend another 40k or until your bank balance runs out. Since holly has done such an effective job of marketing these operators she is either on their pay roll or receiving a significant discount on her inevitable next treatment. Unless you address the underlying disease any benefit of this therapy will be short lived.

There are currently no approved treatments available to help repair damage caused by MS. This type of UK trial is vital if these type of treatments are to become a reality.

My treatment of Autologous HSCT, has seen benefits in my EDSS score. The improvement in my EDSS score was the result of removing the MS disease from my immunity system. It did not remove the underlying MS genetic floor and hence I could relapse. As a consequence, I tell people what I believe is true and that is my disease is in remission. Only a Allogenic HSCT operation could have a chance of doing both. That is remove the disease from the immunity system, along with the genetic floor.

The Autologous HSCT resulted in my immunity system no longer attacking my body. Nerve rebuild and remyelination of the nerves are a natural process if MS is removed from the immunity system. This was demonstrated by my intolerance to heat disappearing overnight. When I received treatment, it was during the Australian summer where 40 °C days are not uncommon. I wore a cooling vest and air conditioning on 24/7 before AHSCT. Now I do not use air conditioner until my husband and daughter need it. There is though a limit to what the natural process will achieve and MSC treatment could be a legitime option if it is backed by legitimate Phase I and Phase II trail research data as we are starting to see in the UK. My EDSS score was 7.0 it has reduced to 4.0 in less than 12 months. Research indicates my EDSS improvement will plateau after 3 years and I am looking at options when the natural process has had the opportunity to achieve its full potential. Considering what I have already achieved in 12 months I am optimistic of what the next 2 years will bring but keep a keen eye on legitimate research.       

The UK trials are replicating what is already occurring at the Cleveland clinic in the US.

 

 http://clinicaltrials.gov/ct2/show/NCT00813969 

 

These MSC trials involve collecting the Mesenchymal Stem Cell from the patient's own bone marrow. This is probably done surgically aspirated from the pelvic bone, but they may also do it by using a mobilization drug (G-CSF) and then perform PBSC collection from the peripheral bloodstream. The collected MSC's are then replicated (culture expansion) ex-vivo (out of the body) over a period of 1-3 months to create a substantially large MSC population. This population would be in the neighbourhood of 1-2 million stem cells per kilogram of body weight. The result of this effort is then re-infused back into the body.

The Cleveland method is being used in a trial being conducted in Israel by two state hospitals under the direction of Dr. Dimitri Karussis. The results are not negative but not positive. This I believe is due to patient selection. You can see that some patients have irregular exacerbations and some have regular exacerbations. Keep in mind that all these trials are at a Phase I trial phase, where they are proving safety rather than curative efficiently of the procedure. I hope that either the Phase II trials or the recently announced UK trials introduce a anomaly in the data by having a patient that has received HSCT treatment.

 

 

 

 
 

 

 

Where to get HSCT treatment.

 

MS Society continue to state that they do not recommend anyone to seek treatment outside clinical trials. I understand this position, considering how many snake oil salesman that are out there willing to take advantage of people by selling a MS Stem Cell treatment, that has no chance of treating their current stage of the disease cycle.

In fact, 95% of the results of a Google search on MS Stem Cell will return results taking readers to treatment center's that are a scam operators. They are selling treatments with very clever marketing. Unless you know what you are looking for, most likely you will taken advantage of. So we fully understand MS Society recommendation.

At the same time though, we feel denying people information of where the legitime treatment center's are, is equally unethical. In doing so, playing part in sealing peoples fate by turning the other cheek.

We strongly recommend our fellow Australians to contact either of the two doctors providing trials here in Australia. Click on the link above or here, Gaining Access to treatment here in Australia. Keep in mind both Dr's are attempting to establish the treatment here in Australia and are cherry picking patients that are 100% certain to prove this treatment effectiveness.

They have strict guidelines to achieve these goals. I have attempted my best, to recall my treating Dr's selection criteria. Those considering AHSCT should not self diagnose. It is better to let the Dr rule you out, rather than yourselves and miss your spot. In addition, you should take into consideration, that we have heard from 3 of the 9 patients from the Perth trial, that the waiting list is at present 2 years for approved patients.

 

The MS Society states that all should participate in controlled trials. As I understand this position, I am not supportive of it. I strongly recommend that other's attempting to gain access, first attempt to gain access here in Australia and then consider overseas treatment.

One warning in doing so, even though the current Phase III trial in Chicago fits within the MS Society recommendations, the treatment costs 157k for approved patients. To be approved you must have meeting with Dr Burt and you MUST have a MRI in his hospital that cost 8k. He has refused to look at MRI's done at other hospitals even if they meet his criteria and are less than 2 weeks old.

There is travel and accommodation costs on top of this. The sad truth is, Burt rejects the majority of candidates. This is due to the fact he is cherry picking patients that will prove his treatment is successful. Those who are approved, then must sign legal commitment to return for 5 years, having 5 MRI's (that cost 8k) so Dr Burt can show his success of the treatment he has developed.

Due to this, we do not recommend him. Although his trial, fits into the MS Society definition of appropriate treatment. Dr Burt is a necessary evil though, as the trail he is completing, will result in this treatment being released in the US and hopefully here in Australia.

We have on our International treatment options page hospitals (one of which is the leading cancer institute in Europe that performs this procedure 200 times a year with a 1% fatality rate, no hospital in Australia could claim these success and number of patient's treated). They consider patients free of charge through emailing patient history and appropriate MRI's for consideration of approval.

The patient has 95% of decision after this consultation through email, and require a final meeting with the doctors before getting the 100% approval. The patient does not pay anything towards treatment until approval is given and they are half the cost of any US FDA approved trial (and hence MS Society approved overseas trial). These treatments though are costly but are half the cost of any trial in the US.

As my husband and I were desperate for AHSCT, especially with a little one, this was definitely plan B for us. This information took a great deal of research to find and we are passing on what we have learnt from these efforts. This was due to not being supplied it from the MS Society or treating neurologist.

We believe people should involve their families and loved ones. Watch my videos and you will see it is an intense treatment not to be taken lightly. I do not believe taking patients decisions for them, by hiding and denying information. In acting in such a manner, I would be partly responsible for their fate, if they were not given the information to decide for themselves. Once again, this is about empowering the Ms sufferer and their loved ones. So much power is taken from us with this disease. It is about time, more power is given back to us for a better quality of life, Alleluia.

 

Of course, I am speaking to my fellow Australian's and all my fellow MS'ers, no matter were you are on the planet. Treatment options in Australia and International Treatment Options.

 

 

 Other HSCT blogs

There are as mentioned, 600 people that have had HSCT for Ms. Some of them keep a blog, in their endeavours to gain treatment and educate people of AHSCT and their recovery after treatment. Here are some of them.

 

The undisputed best blog of HSCT for MS is that of George Goss

http://themscure.blogspot.com/

 

http://marcstemcell.com/blog/

 

http://lisashope.com/blog/

Lisa web site is really well designed. We recommend all those that are contemplating a personal appeal to look at Lisa's web site.

 

http://www.sandiselvi.com

 

 

There is another gentleman, David in the US that has had the same procedure as myself that runs an excellent forum for MS people in the US called Active MS'ers

http://activemsers.wssnoc.net/index.php

and he has Blog located here

http://www.activemsers.org/

 

Stella log

http://www.msrc.co.uk/index.cfm/fuseaction/show/pageid/3181

 

 

 

 

 

 

 

 

 

 

 

   


 

     




 

 

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