SUBIECT: Wise Young "TVM: Se afla 'vindecarea' in China?"

Prezentarea Doctorului Wise Young - "The Spinal Cord Workshop", Bedford Stem Cell Research Foundation, 2008









Am creat acest thread separat, deoarece vreau sa vin cu unele linkuri la pagini sau lucrari de specialitate mentionate in video, si de asemenea sa lucram la versiunea finala a subtitrarii.

Astept comentariile voastre.

La doi ani si jumatate dupa ce am facut un transplant de celule stem in China (cel putin asa pretinde medicul Huang Hongyun),cand in sfarsit acceptasem ca aceste ''transplanturi'' nu ajuta,iese in fata dr-ul Wise (desi nu a iesit chiar acum,clipul a fost postat pe Youtube in 28 mai 2008) si ma face sa trec din nou prin cateva emotii.Scepticism,apoi speranta.....totusi,si iarasi furie pentru ca am fost pacalita sa platesc pentru a fi un cobai,si disperare ca daca va aparea un tratament,o cura,de unde bani...si de aceasta data cine stie cati......Si-atunci sa spun ''gata,nu mai vreau sperante desarte''?......Sa ma consolez cu situatia data?
Eu spun ''Faca-se voia ta,Doamne''

LUMINITA a scris:Or sa mai treaca ceva ani buni pana cand pacientii cu TVM cronic vor avea sanse de a spera la indeppendenta... oricum, teste si cercetari se fac, ramane sa vedem ce ne aduce nou Dionnis in acest thread
Amin.

PS. Bine ai revenit, vindecare rapida a problemelor tale si nu uita... esti 'caramida' cu folos a acestui site... pupici

Luminita a scris:[/b]
Clipul a fost postat pe Youtube acum cateva zile de mine, ca i-am facut traducerea. Conferinta a avut loc in 2008. Nu stiu exact cand a fost postat pe internet, dar cred ca in urma cu doi ani.

Am deschis acest thread ca sa discutam si corectam greselile in traducere, si pentru a aduce in discutie unele dintre lucrurile pe care le zice Wise.

Pe Wise l-am urmarit, pe forumul Carecure, cred ca de vreo 7 ani, si mereu si-a mentinut o pozitie constanta - 'Nu exista 'vindecarea'(cure) ...inca.' Wise e la baza neurochirurg, dar apoi si-a dedicat viata cercetarii. Face cercetari pe sobolani in SUA. Singurul medicament aprobat de FDA-ul american pentru a fi folosit in TVM, care e standard acuma in SUA, a fost descoperit de Wise, trecut prin teste clinice in mai multe faze etc. Nu aduce multe imbunatatiri, conform statisticilor - pana in 20% pt. cazuri incomplete, pana in 8% pt. cazuri complete, dar in SUA e procedura standard. In alte tari, e la decizia doctorului daca sa-l administreze sau nu, luand in considerare starea generala a pacientului.
Wise deasemenea e cel care a introdus "contusion model" in cercetarea pe sobolani.
Pe scurt, e cineva care militeaza pentru gasirea unei vindecari pentru TVM, -aduna fonduri, face cercetare etc.- si din cate am vazut eu isi mentine o pozitie constanta si realista.

Videoul e luat de aici: https://spinalcordworkshop.org

Bedford Stem Cell Research Foundation, e o organizatie non profit infintata decatre Dr. Ann A. Kiessling, care printre altele, incurajeaza cercetarea pentru a gasi un remediu TVM. Femeia asta e tare si ea ..vedeti in biografie, si-i aduna pe cei mai buni in domeniu, pentru a incerca sa miste lucrurile inainte. Acuma a fost o conferinta si-n 2010, dar inca nu au pus videourile la aia. Mai este un video cu Wise in 2009, dar in mare repeta ce a zis si-n 2008. In 2009 lucrul nou e ca a infintat o retea TVM in SUA.

Videoul din 2008, mie mi s-a parut interesant, deoarece prezinta f. pe scurt, majoritatea lucrurilor ce se intampla in cercetare, si realitatea din sistemul medical american si cel chinez. As mai traduce si altele, dar traducerea merge foarte greu.

Ma lungesc prea mult la vorba. Am vrut sa atasez fisierul cu traducerea, dar nu am reusit, de aia am sa-i dau un copy paste aici, si le voi lua pe rand.

[EDIT ...nu pot sa-l bag copy paste...ca e prea lung, si-l pune doar pe jumatate. Daniel, poate-mi explici cum sa-l atasez: aleg un fisier pentru a-l atasa, apas [fisier] ...dar nu-mi iese.Mersi.]


***

Pentru inceput mentionez trei lucruri care mi s-au parut interesante:

1.https://www.chinascinet.org Asta e pagina Retelei TVM din China, infintata de Wise, in care sunt membri mai multe spitale chineze. Fac 'teste clinice', nu cer bani, si nu ofera vindecarea.

Fac teste clinice pentru o combinatie intre un transplant de celule din sange al cordonului ombilical, + administrare de Litiu si probabil Methylprednisolone. Aceste teste clinice, sunt acum in desfasurare. Din cate am inteles pe forumul lui Wise, deocamdata o 'incidental observation' (o observatie accidentala? ...nu stiu cum sa traduc asta), e ca Litiu ajuta la ameliorarea Durerii Neuropate. Sa vedem ce rezulatate vor avea pe final. ..acum recrutau pacienti pentru testul clinic CN102B.

2. Decompresare intra-medulara pentru cazuri acute la Chengdu Army Kunming General Hospital

Pe majoritatea nu-i intereseaza acest subiect, deoare nu-i vorba de cazuri cronice. Totusi daca exista o metoda care da rezultate, pentru cei noi accidentati, nu am vrea sa afle si doctorii nostri despre ea? Probabil ca deja stiu ...cel putin sper.
Din 30 de pacienti, Asia A, 54% au recuperat mersul. Pacienti operati intre 2 - si 65 de zile de la accident.

3. Christopher & Dana Reeve Foundation - Test Clinic cu medicamentul 'Riluzole'

Wise mentioneaza in video, asta in 2008, ca a auzit ceva despre un astfel de test clinic. Am cautat pe net, sa vad daca a pornit, si pe 12 Aprilie 2010, au recrutat pacienti pentru Test Clinic Faza 1, (sa se asigure siguranta). Acesta e un alt test clinic, care trebuie urmarit.

https://www.christopherreeve.org/site/c.ddJFKRNoFiG/b.4435063/k.4B8F/Reeve_Foundation_North_American_

"NEWS UPDATE - April 13, 2010: The Reeve Foundation's North American Clinical Trials Network (NACTN) enrolled the first patient into its Riluzole Phase I safety study yesterday evening. NACTN, which is supported by a grant from the Department of Defense, has spent months planning and preparing for this clinical trial. This is an acute injury trial, which means that only patients who are newly injured, treated in the Emergency Room at a NACTN site and meet the inclusion/exclusion criteria can be enrolled.

Riluzole, a neuroprotective drug, is presently used in the treatment of amyotrophic lateral sclerosis where it prolongs the life spans of patients. It acts by blocking the ability of sodium and calcium ions to enter and damage neurons and glia. Laboratory studies have shown it to be effective in limiting traumatic damage to the spinal cord.

The Phase I study will evaluate safety of riluzole in acutely injured spinal cord patients; it will also investigate its pharmacodynamics (biochemical and physiological effects) and pharmacokinetics (what the body does to it). The trial will also collect information about its efficacy as measured by ASIA (motor and sensory outcomes), ASIA Impairment Grade and Brief Pain Inventory."

****

Mai sunt si alte puncte interesante din video, la care pot veni cu linkuri... am salvat linkurile akasa cred. Deocamdata am incarcat postu asta prea tare.

Sper ca pot avea discutii pe text, cu cei ce stiu engleza, pentru a corecta greselile. Nu incerc sa dau sperante desarte la nimeni, ci cred doar ca acestea sunt lucruri pe care trebuie sa le urmarim.

Spor.

Tot respectul Dionnis ,m-am uitat la textul tradus si nu am remarcat greseli majore.Sa dea bunul Dumnezeu sa se descopere o vindecare cat mai curand.

Mersi.

Cateva din nelamuririle pe care le am, poate le elucidam:

"adhesions" - nu sunt sigur asupra acestui cuvant, care ar fi traducerea corecta.Noi l-am tradus prin "cicatrici".

Adhesions are fibrous bands that form between tissues and organs, often as a result of injury during surgery. They may be thought of as internal scar tissue.
en.wikipedia.org/wiki/Adhesion_(medicine)

Nu sunt sigur, deoarece zice despre "remove adhesions" din afara spinal cord. Poate-s bucati de os.. etc. Sau sunt cicatrici in exteriorul maduvei?

***
In doua locuri vorbeste despre "lateral myotomy" [sau cel putin asa imi pare mie ca spune]. Am tradus prin "miotomie". Dar din nou nu sunt sigur, deoarece "Myotomy describes a surgical procedure in which a muscle is cut." si acolo era vorba de a taia in maduva spinarii, care desigur nu-i un muschi.

***
"intrathecally" ..l-am tradus prin 'punctie'. Desi "intrathecally" are un inteles mai larg.
i
ntrathecal /in·tra·the·cal/ (-the´k'l) within a sheath; through the theca of the spinal cord into the subarachnoid space.

Intrathecal
Introduced into or occurring in the space under the arachnoid membrane which covers the brain and spinal cord.

****

Diferente dintre: "open up the spinal cord" si "expoze the spinal cord".

Open up- a deschide maduva spinarii, a taia in maduva.

Expoze - a expune maduva.
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[standardized outcome measures] am tradus prin "evaluari standard ale rezultatelor" poate exista o deifinitie mai buna.


***

"Hemisectioned spinal cord" am tradus prin semisectionata ...dar poate exista o formulare mai buna.

Desi am inteles "contuzioned spinal cord", nu am inteles exact diferenta intre hemisectioned si transectioned spinal cord.

***

Cd34 enriched cells -- tradus prin "imbogatite", dar poate exista un termen mai bun.

***

"unmatched HLA cells" ..am tradus prin fara a se verifica compatibilitatea, dar nu e asta definitia corecta.

Nu gasesc un cuvant in romaneste care sa se potriveasca mai corect. Idei?

***

'cell culture media' ..cum traducem "media"?

***

Dorsal Root Entry Zone - am tradus prin Calea Radacinii Posterioare. poate ar trebui Punctul de intrare al Radacinii Posterioare. Nu sunt sigur care-i semnificatia "caii".

Cam atat deocamdata. Daca aveti vreo idee, let me know.

Am mai facut unele modificari, si versiunea finala am bagat la trilulilu aici:

https://www.trilulilu.ro/Eqqqu/ee0025f89175ff

Adaug aici si subtirarea in caz ca o vrea cineva, ca se poate sa o pierd...I-am schimbati terminatia in .txt, sper sa se incarce de data asta

La unele dintre problemele mentionate anterior am gasit solutia:


'cell culture media' ..cum traducem "media"? ... e 'mediu de cultura'

***

enriched ...e corect cu imbogatite

***

"unmatched HLA cells" am tradus prin 'necompatibilizate' ...desi suna putin aiurea, imi pare cel mai aproape.

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"diferenta intre hemisectioned si transectioned spinal cord." hemisectioned am tradus prin hemisectionata. E vorba ca maduva e taiata, pana la jumatate.
Transectioned ...e atunci cand e taiata, sectionata complet.

***

intrathecally. ..a ramas punctie, din cate inteleg eu, cand se face injectia acul trece prin dura mater, dar nu de pia mater. Nu patrunde in Substanta Alba.

E la fel ca in video pus de Daniel pe site.


***

Referitor la intrebarea lui cosmin0040, din alt thread.

In momentul de fata, din ce am citit, am aflat urmatoarele: Wise si cei de la https://www.chinascinet.org/, sunt in stadiul de a recruta 20 de pacienti pentru testul clinic CN102B.

Testeaza siguranta. Wise vorbeste si despre test si-n video. Testul clinic a fost afisat si la clinicaltrials.gov, care este un site oficial al National Institute of Health - SUA. https://clinicaltrials.gov/ct2/show/NCT01046786

Verified by China Spinal Cord Injury Network, January 2010
Detailed Description:

This is an open-label, dose-escalating clinical trial. Three groups of four patients will receive transplants of increasing doses of HLA-matched umbilical cord blood mononuclear cell into the spinal cord. In the fourth group, we will transplant the highest volume of cells that did not increase neurological deficits along with a single bolus of 30mg/kg methylprednisolone sodium succinate. In the fifth group of four subjects, we will inject that volume of cells plus a bolus intravenous dose of 30mg/kg methylprednisolone sodium succinate and a 6-week course of oral lithium carbonate titrated to 0.6-1.0 mM serum levels. All the subjects are encouraged to stand or walk for one hour a day after the cell transplantation.

The neurological and walking outcomes will be assessed 3 days, and 1, 2, 6, 24 and 48 weeks after transplantation. The outcomes of the five treatment groups will be compared by analysis of variance and, if possible, correlation with cell dose. Efficacy and safety will be analyzed comparing neurological change scores amongst the five different treatment groups. Loss of motor (>5 points) or sensor scores (>2 points) from baseline pre-treatment levels would be considered deleterious. Increases in scores above baseline would be considered beneficial.


***


Doua threaduri in care Wise vorbeste despre ultimele nouatati sunt aici:

https://sci.rutgers.edu/forum/showthread.php?t=129584

https://sci.rutgers.edu/forum/showthread.php?t=129837


Vreau sa fac un copy paste, sa ramana aici chiar daca e in engleza:

****

Lunasicc42,

Let me describe the differences not only of the therapies but differences of the approaches taken by Beike and ChinaSCInet.

1. Commercial product versus clinical trial. Beike is selling an unproven therapy and is profiting from the therapies. ChinaSCINet is doing clinical trials of therapies and does not charge subjects. Beike claims that their therapies work (80% of the time was the claim on CareCure) even though they have no evidence that this is so. We say that we don’t know whether the therapies work until clinical trials are done.

2. CD34+ cells versus mononuclear cells. Based on information sent to me by patients who have gone there, Beike is growing umbilical cord blood cells that express the CD34+ marker from fresh human umbilical cord blood. CD34 is a marker for hematopoietic cells and endothelial progenitor cells. In contrast, ChinaSCINet is transplanting umbilical cord blood mononuclear cells that include CD34+, CD133+, CD45+, and other markers.

3. Non-HLA-matched versus HLA-matched. Beike cells are not HLA-matched to recipients. HLA stands for human leukocyte antigen. Cells that are not HLA-matched are usually rejected by the immune system. ChinaSCINet is using cells that match at least 4 of 6 HLA. When umbilical cord blood cells are used for bone marrow transplants, about 80% of 4:6 HLA matched cells engraft while 100% of 6:6 HLA matched cells should engraft. Unmatched cells usually will not engraft.

4. Intravenous/intrathecal administration versus intraspinal administration. Beike is giving non-HLA-matched CD34+ umbilical cord blood cells intravenously or intrathecally to patients. ChinaSCINet is making four injections of 4, 8, or 16 µliters of cells (100,000 cells per µliter) into the spinal cord, i.e. 1.6, 3.2, and 6.4 million cells, above and below the injury site. Our transplants will contain cells that express CD34, CD133, and other markers of stem cells.

5. No lithium versus lithium. Beike is just giving the cells intrathecally or intravenously. ChinaSCINet is testing the difference between transplanting the cells into the spinal cord and transplanting the cells followed by a 6-week course of oral lithium that is carefully titrated so that the subjects have 0.6 mM and 1.0 mM serum levels.

Many animal studies suggest that umbilical cord blood mononuclear cells improve neurological recovery in rats after spinal cord injury. In 2003, Saporta, et al. [1] reported that intravenous infusion of human umbilical cord blood cells to rats improves neurological recovery after spinal cord injury. In 2004, Zhao, et al. [2] found that intraspinal transplantation of CD34+ human umbilical cord blood cells improves functional recovery in adult rats after spinal cord hemisection. In 2005, Kuh, et al. [3] reported functional recovery in rats after spinal cord contusion (NYU Impactor) and human umbilical cord blood cell were transplanted into the spinal cord, when the transplants were given with brain-derived neurotrophic factor (BDNF). In 2006, Nishio, et al. [4], using the Impactor, reported that human umbilical cord blood enriched with CD34+ cells survived in rats for at least 3 weeks after transplantation but disappeared by 5 weeks but nevertheless improved the volume of surviving white matter and locomotor function of the rats. In 2007, Dasari, et al. [6] reported that human umbilical cord blood mononuclear cells survived for at least two weeks and enhanced remyelination in the spinal cord of rats after contusion injury. In 2008, Dasari reported [7] that the cells reduced expression of fas and prevented death of neurons [8]. In 2008, Cho, et al. [9] reported that neurally induced human umbilical cord blood cells produce nerve growth factors and promoted functional recovery in rats with spinal cord injury, including somatosensory evoked potentials. In 2009, Kao, et al. [10] found that CD34+ human umbilical cord blood injected intravenously into the tail veins of rats after spinal cord compression improved ability of the rats to climb an inclined plane and that CD34+ cells produce the growth factors GDNF and VEGF in the spinal cord while non-CD34+ cells did not. Finally, Lee, et al. [11] recently described a method of human umbilical cord blood mononuclear cells into the spinal cord of dogs and 3 of 4 dogs that received the cells improved locomotor function after 3 weeks.

I have reviewed the literature on lithium treatment of spinal cord injury before and will not do it here except to say that lithium may improve neurological function in rats when given shortly after injury but it does not seem to do so when given to animals and people with chronic spinal cord injury. We have completed one phase 1 lithium clinical trial in 20 patients with chronic spinal cord injury and found the treatment to be safe (submitted for publication). In a recently completed double-blind randomized clinical trial, we confirmed that a 6-week course of oral lithium is safe and does not improve neurological function in people with chronic spinal cord injury but surprisingly noted that a majority of people who received lithium showed a significant reduction in neuropathic pain. We are planning on a further clinical trial to confirm that finding. Of course, when we do the clinical trial of umbilical cord blood monunuclear cell transplant plus lithium, we will be looking for any reduction in neuropathic pain. We are planning a clinical trial in the United States that will include one treatment arm that will have lithium only.

In other studies, we have shown that lithium strongly stimulates umbilical cord blood cells to produce neurotrophins (including NGF, NT3, and GDNF) both in vitro (in the culture dish) and in vivo (after transplantation into the spinal cord. At the same time, we found that administration of cyclosporin or other calcineurin inhibitors completely abrogated this effect of lithium in animals. In our experiments, if calcineurin inhibitors are not given, transplanted human umbilical cord blood or non-HLA matched rat neonatal blood do not survive longer than 4 weeks. So, it was not possible for us to duplicate in rats the treatment that we want to do in humans. We have shown that injecting a single bolus of methylprednisolone increased the length of survival of transplanted cells. We are currently carrying out experiments with a special rat strain called Fischer rat where we can transplant cells from one animal to another without immunosuppression.

What our phase 1/2 trial of umbilical cord blood cell, methylprednisolone, and lithium treatment of chronic spinal cord injury will hopefully show are:
1. the transplants and the procedure are safe.
2. the transplanted cells improve neurological function.
3. giving a bolus of methylprednisolone along with the cell transplants improve neurological function more.
4. giving a 6-week course of lithium along with the cells will improve neurological function even more.

Please understand that I don’t know what the results of the trial will be. Nobody has ever done these combination treatments in humans before. While Beike claims to have gotten improvement of patients after giving non-HLA-matched CD34+ cells intravenously, I am very skeptical of these claims. Our trial may show variable neurological improvement, even though all the patients are ASIA A, so that we will not see a statistically significant trend of improvement with greater umbilical cord blood dose, methylprednisolone, and lithium. Our trials may show significant improvement associated with the cell transplants. We don’t know. That is why we are doing the clinical trial.

Wise.

****

E prea mult de tradus. Foarte pe scurt: sunt in procesul de a recruta 20 de pacienti, TVM complet ASIA A, cronic [mai mult de un an de la accident], ii impart in mai multe grupe. Trebuie sa compatibilizeze si HLA, cel putin 4 din 6 gene.

Fac tratamente combinatorii.

Fac laminectomie, apoi injecteaza direct in maduva, in puctul de intrare al Radacinii Posterioare celule UBC din sange ombilical. Cantitatile care vor fi injectate vor fi diferite de la grup.

La unii li se va administra si methilpredinsolone si litiu.

In primul rand se testeaza siguranta, dar in functie de rezultate vor vedea daca merg mai departe. Urmatoarea faza e un test clinic cu 400 de pacienti.

Astept sa iasa videourile de la ultima conferinta, din Taiwan, ..sa vedem ce mai zic acolo.

Nu se stie ce rezultate vor avea. Sa vedem.

Am dat azi pe la Care Cure, sa vad ce se mai intampla.

A inceput si testul clinic al lui Wise. Cel de care vorbeam mai sus.

Pe 29 Noiembrie, au avut primul implant la Hong Kong. Din cate am inteles vor mai avea 19 pacienti la Hong Kong si 20 la Kunming, China.


https://sci.rutgers.edu/forum/showpost.php?p=1290098&postcount=104

12-01-2010, 05:15 AM #104
Wise Young
Administrator

Join Date: Jul 2001
Location: New Brunswick, NJ, USA
Posts: 36,016

The first case was one on the 29th of November. It was, I believe, the first spinal cord injury cell transplant operation in Hong Kong history. The surgery went well. The patient did not have any neurological change afterward. In addition to the daily care and exams, the subject will be receiving formal examinations at 6 weeks, 6 months, and a year. I am hopeful, of course.

The next case has been tentatively scheduled for around the middle of December.

Wise.


O traducere pe fuga:

"Am avut primul caz pe 29 Noiembrie. Cred ca a fost primul transplant de celule stem, din Hong Kong. Operatia a decurs bine. Pacientul nu a prezentat schimbari neurologice dupa operatie. Pe langa ingrijirea si examinarile zilnice, subiectul va fi examinat la 6 saptamani, 6 luni si un an. Desigur, am sperante.

Urmatorul caz a fost programat pentru jumatatea lui Decembrie.

Wise."

In prezent sunt doua teste clinice care au pornit. Cel al lui Geron, si asta al lui Wise.

Sa vedem ce iese. Inca nu au dat vreun comunicat oficial.

Mai vreau sa fac cateva precizari. Sper sa nu complic lucrurile, ci sa le simplific.

Am sa mai pun si unele chestii in engleza, deoarece vreau sa le revad in viitor, si sa vad diferentele. Uneori, cu trecerea timpului, dispar de la linkurile originale si nu le mai gasesc.

Ultima versiune a traducerii conferintei din 2008, a urcat-o si Daniel la Youtube. Nu am sa sterg prima versiune, cea care e la inceputul acestui thread, sa se poata vedea diferentele. La ultima versiune, am bagat diacritice si am mai facut unele modificari.









Nu mai stau sa caut exact minutul in care vorbeste despre aceste teste clinice, dar redau din subtitrare:

00:49:46,671 --> 00:49:50,232
Tocmai am inceput acest test,

655
00:49:50,232 --> 00:49:53,636
un test in faza 2 pentru litiu;

656
00:49:53,636 --> 00:49:56,213
e un 'test clinic aleatoriu dublu orb' faza 2 ,

657
00:49:56,213 --> 00:49:58,180
pentru a determina eficacitatea litiului adminstrat pe cale orala,

658
00:49:58,180 --> 00:50:00,951
pe 40 de pacienti cu TVM cronic.

659
00:50:00,951 --> 00:50:03,474
Acesta se desfasoara la China Rehabilitation Research Center.

660
00:50:03,474 --> 00:50:08,976
In final, ne aflam in stadiul in care facem aplicatii la guvernul chinez, pentru acest studiu,

661
00:50:08,976 --> 00:50:13,129
pentru a transplanta celule mononucleare din sange .

662
00:50:13,129 --> 00:50:16,770
Si acesta e un studiu "dose-response curve"

663
00:50:16,770 --> 00:50:21,431
Am avut o conferinta pentru a cadea de acord cum e mai bine sa injectam celulele

664
00:50:21,431 --> 00:50:23,773
si am decis ca cea mai buna metoda pentru a injecta celulele

665
00:50:23,773 --> 00:50:27,344
este la un unghi de 45 de grade, in Calea Radacinii Posterioare [Dorsal Root Entry Zone],

666
00:50:27,344 --> 00:50:29,499
deasupra si sub zona lezata.

667
00:50:29,499 --> 00:50:31,654
Pentru a evita toate Tracturile din Subtanta Alba,

668
00:50:31,654 --> 00:50:35,680
începem cu injectii de 4 microlitri,

669
00:50:35,680 --> 00:50:38,952
apoi 8 microlitri, dupa care injectii de 16 microlitrii,

670
00:50:38,952 --> 00:50:43,657
si acestea contin aproximativ 100.000 de celule in fiecare microlitru.

671
00:50:43,657 --> 00:50:47,551
Dupa ce am facut asta - 4 pacienti in fiecare grupa,

672
00:50:47,551 --> 00:50:51,527
aceasta se numeste "accelerated dosing trial paradigm".

673
00:50:51,527 --> 00:50:59,485
Apoi vom face injectia de 16 microlitri, plus Methylprednisolone.

674
00:50:59,485 --> 00:51:02,641
Am aratat ca atunci cand administram o singura pilula de Methylprednisolone,

675
00:51:02,641 --> 00:51:06,753
crestem rata de supravietuire a celulelor de aproape 4 ori dupa o injectie.

676
00:51:06,753 --> 00:51:10,231
Si apoi, dupa ce facem asta, si vom arata ca nu prezinta pericole,

677
00:51:10,231 --> 00:51:11,165
vom trece la pasul final,

678
00:51:11,165 --> 00:51:14,987
care este: transplat de celule, plus Methylprednisolone, plus Litiu.

679
00:51:14,987 --> 00:51:21,368
Toate acestea au ca tinta un "studiu clinic faza 3",

680
00:51:21,368 --> 00:51:27,783
în care vom avea 400 de pacienti si le vom tranplanta celule mononucleare,

681
00:51:27,783 --> 00:51:31,142
dupa care ii vom alege aleatoriu pentru administrare sau fãrã administrare de Litiu.

682
00:51:31,142 --> 00:51:33,489
Oamenii m-au intrebat: "De ce v-ati facut planul in modul acesta?"

683
00:51:33,489 --> 00:51:38,393
Stiu ca in China nu cred ca pot convinge pe nimeni sa faca un 'sham surgery control'.

684
00:51:38,393 --> 00:51:40,640
Nimeni nu ar fi de acord cu asa ceva.

685
00:51:40,640 --> 00:51:48,474
În esenta, facem un studiu in care transplantam celule la 400 de pacienti,

686
00:51:48,474 --> 00:51:51,359
apoi ii alegem aleatoriu pentru Litiu.

687
00:51:51,359 --> 00:51:53,415
Care sunt rezultatele posibile ale acestui studiu?

688
00:51:53,415 --> 00:51:58,750
Unul dintre rezultate ar putea arata ca nici un tratament

689
00:51:58,750 --> 00:52:02,900
nu arata vreo imbunatatire, comparativ cu conditia de dinainte de tratament.

690
00:52:02,900 --> 00:52:05,742
În acest caz asta ar fi ceva foarte negativ

691
00:52:05,742 --> 00:52:08,492
si nu as recomanda aceasta terapie nimanui.

692
00:52:08,492 --> 00:52:12,254
Un rezultat negativ e foarte puternic.

693
00:52:12,254 --> 00:52:18,425
Daca ni se dovedeste ca transplantul de celule + Litiu e mai bun decat doar transferul de celule,

694
00:52:18,425 --> 00:52:23,650
atunci am putea propune folosirea tratamentului format din transplant de celule + Litiu.

695
00:52:23,650 --> 00:52:25,922
Pentru ca a fost un studiu aleatoriu.

696
00:52:25,922 --> 00:52:31,143
Daca ni se arata ca atat transplantul de celule, cat si transplantul de celule + Litiu,

697
00:52:31,143 --> 00:52:35,224
aduc imbunatatiri comparativ cu conditia de dinainte de tratament,

698
00:52:35,224 --> 00:52:40,083
atunci nu putem sa dovedim ca aceste imbunatatiri nu se datoreaza doar operatiei

699
00:52:40,083 --> 00:52:49,679
si atunci va trebui sa mai facem un studiu clinic ca sa dovedim ca imbunatatirile sunt aduse de transplantul de celule.

700
00:52:49,679 --> 00:52:56,096
Eu m-am gandit ca daca vom avea acest rezultat,

701
00:52:56,096 --> 00:53:04,105
acela ca atat transplantul de celule din sangele ombilical... cat si transplantul de celule ombilicale + Litiu, arata imbunatatiri,

702
00:53:04,105 --> 00:53:06,089
sau ca ambele par sa arate aceleasi imbunatatiri,

703
00:53:06,089 --> 00:53:08,366
urmatorul test clinic pe care l-am face constã în

704
00:53:08,366 --> 00:53:11,774
compararea altui tip de celula cu celulele din sange al cordonul ombilical.

705
00:53:11,774 --> 00:53:15,039
Abia apoi vom avea cateva raspunsuri.

706
00:53:15,039 --> 00:53:19,778
Sunt multe constrangeri in China, si cred ca si in SUA este valabil,

707
00:53:19,778 --> 00:53:25,232
si este foarte dificil sã se creeze un grup placebo.

708
00:53:25,232 --> 00:53:26,750
Ar fi foarte dificil.

709
00:53:26,750 --> 00:53:33,204
Ipotezele ar trebui sa fie destul de clare.

710
00:53:33,204 --> 00:53:41,745
Studiul CN100 e sa arate ca centrele pot aduna informatii despre pacienti pe perioada unui an,

711
00:53:41,745 --> 00:53:47,328
Studiul CN101 este pentru a arata ca Litiu administrat oral nu prezinta complicatii,

712
00:53:47,328 --> 00:53:52,906
CN102, pentru a arata daca Litiul are ca efect imbunatatirea neurologica,

713
00:53:52,906 --> 00:53:58,973
CN102b, ca sa arate daca e sigur sa se transplanteze celule in maduva spinarii,

714
00:53:58,973 --> 00:54:01,836
si CN103, este pentru a dovedi daca terapie combinatorie este eficienta.

***

Pe 29 noiembrie au inceput testul clinic CN102b.

Redau si in engleza informatiile despre acest test:

Clinical Trial CN102b Information
The clinical trial CN102B "Safety and Feasibility of Umbilical Cord Blood Cell Transplant into Injured Spinal Cord: an Open-Labeled, Dose-Escalating Clinical Trial" is now open for subject recruitment. Dr Gilbert Leung and Dr Yat-wa Wong from The University of Hong Kong (HKU), Prof. Wai-sang Poon from The Chinese University of Hong Kong (CUHK), and Prof. Wise Young from ChinaSCINet and The State University of New Jersey (Rutgers, USA) are the principle investigators of the trial. This trial was started in early March 2010.

The trial details have been posted on https://clinicaltrials.gov/ct2/show/NCT01046786. Briefly, the trial will recruit 20 subjects with chronic traumatic spinal cord injury at C5 and T10 levels inclusive (more than one year after injury with stable neurological function); who are classified on the ASIA Impairment Scale as A (“complete” spinal cord injury); who do not have significant contraindications to the surgery, methylprednisolone or lithium; and for whom we can find an umbilical cord blood unit that matches at least 4:6 human leukocyte antigens (HLA) -A, -B, and -DR. The institutional review boards (IRB) of HKU and CUHK, and Hong Kong Department of Health have approved the trial.

The subjects will be enrolled into five treatment groups and four subjects for each group. The first three groups will receive respectively 4, 8, and 16µliters of 100,000 HLA-matched mononuclear cells/µliter. Cells will be transplanted by four injections 3mm-deep into dorsal root entry zones of spinal cord above and below the injury site. The fourth group will receive the highest safe transplant volume plus an intravenous bolus of 30 mg/kg methylprednisolone to improve the survival of transplanted cells. The fifth group will receive the transplant, methylprednisolone, and a 6-week course of oral lithium carbonate titrated to serum levels of 0.6 to 1.0 mM. Lithium stimulates the cell growth, produces growth factors and hence stimulates regeneration.

StemCyte, a US cord blood bank, will donate the HLA-matched human umbilical cord blood cells. The units have been tested extensively to rule out diseases. A highly-certified U.S. laboratory (Vista Biologicals) will thaw, isolate, and purify mononuclear cells from the units. These cells include CD34+ and CD133+ stem cells in umbilical cord blood. The cells will be shipped from the United States to Hong Kong without culturing or growing of the cells. Stemcyte units are certified by National Marrow Donor Program criteria for safety of transplantation to treat other conditions.

The surgical operation will be performed by Prof. Wai-sang Poon from Prince of Wales Hospital (The Chinese University of Hong Kong) and Dr. Gilbert Leung from Queen Mary Hospital (The Hong Kong University). The hospitalisation period will be within the discretion of the principal investigators which is probably be one week. Rehabilitation will be voluntary after transplantation. Follow-up assessment will be performed at second-week, six-week, six-month, and twelve-month after transplantation. Some of the assessments will be conducted at the MacLehose Rehabilitation Centre.

The trial aims to assess the feasibility and safety of transplanting umbilical cord blood cells into the spinal cord in subjects with chronic spinal cord injury. During transplantation, the injection may cause local damage to the spinal cord. Such damage is unlikely at the small volumes (4-16 µliters) that will be injected. In China, patients routinely get more than 35µliter cell injections into spinal cord without neurological loss. Cell transplants may cause inflammation or meningitis but this is unlikely because the cells are extensively tested to rule out infectious disease and are HLA-matched to reduce the likelihood of immune rejection. During the first week after transplantation, the subjects will be closely monitored in hospital for neurological changes and adverse effects. After discharged, neurological function will be closely monitored at six-week, six-month and twelve-month after implantation to monitor the performance progress.

The trial is based on data from multiple animal studies indicating that umbilical cord blood mononuclear cells (UCBMC) transplanted into spinal cord are well-tolerated can improve function in animals after spinal cord injury. Methylprednisolone may increase the survival of transplanted cells and lithium stimulates umbilical cord blood mononuclear cells to produce growth factors (neurotrophins) that stimulate regeneration in the spinal cord. Based on the results of this phase I/II trial, a phase III trial will be decided and planned to evaluate the efficacy of umbilical cord blood mononuclear cells with and without methylprednisolone and lithium.

https://www.chinascinet.org/index.php?option=com_content&task=view&id=125&Itemid=167


Sper ca nu m-am lungit prea tare.

https://sci.rutgers.edu/forum/showthread.php?t=139662&page=20

12-25-2010, 04:36 PM #199
Wise Young
Administrator

Join Date: Jul 2001
Location: New Brunswick, NJ, USA
Posts: 36,071

Merry Christmas. We are continuing with the trial in Hong Kong. The third case was done on the 23rd of December. Results will not be available for at least 6 months. Wise.

"Craciun Fericit. Continuam testul clinic din Hong Kong. Al treilea pacient a fost operat pe 23 decembrie. Rezultatele vor fi publice dupa cel putin 6 luni. Wise."