{"id":8094,"date":"2016-06-05T08:15:35","date_gmt":"2016-06-05T08:15:35","guid":{"rendered":"http:\/\/www.kurzweilai.net\/?p=281406"},"modified":"2016-06-07T05:08:20","modified_gmt":"2016-06-07T05:08:20","slug":"chronic-stroke-patients-safely-recover-after-injection-of-human-stem-cells","status":"publish","type":"post","link":"https:\/\/hoo.central12.com\/fugic\/2016\/06\/05\/chronic-stroke-patients-safely-recover-after-injection-of-human-stem-cells\/","title":{"rendered":"Chronic stroke patients safely recover after injection of human stem cells"},"content":{"rendered":"<p><iframe frameborder=\"0\" height=\"290\" scrolling=\"no\" src=\"http:\/\/www.washingtonpost.com\/video\/c\/embed\/88637f80-29b7-11e6-8329-6104954928d2\" width=\"480\"><\/iframe><br \/>\nInjecting specially prepared human adult stem cells directly into the brains of chronic stroke patients proved safe and effective in restoring motor (muscle) function in a small clinical trial led by\u00a0<a href=\"http:\/\/med.stanford.edu\/\" >Stanford University School of Medicine<\/a>\u00a0investigators.<\/p>\n<p>The 18 patients had suffered their first and only stroke between six months and three years before receiving the injections, which involved drilling a small hole through their skulls.<\/p>\n<p>For most patients, at least a full year had passed since their stroke \u2014 well past the time when further recovery might be hoped for.\u00a0 In each case, the stroke had taken place beneath the brain\u2019s outermost layer, or cortex, and had severely affected motor function. \u201cSome patients couldn\u2019t walk,\u201d Steinberg said. \u201cOthers couldn\u2019t move their arm.\u201d<\/p>\n<div id=\"attachment_281521\" class=\"wp-caption aligncenter\" style=\"width: 485px;  border: 1px solid #dddddd; background-color: #f3f3f3; padding-top: 4px; margin: 10px; text-align:center; display: block; margin-right: auto; margin-left: auto;\"><img class=\" wp-image-281521\" title=\"Sonia Olea Coontz\" src=\"http:\/\/www.kurzweilai.net\/images\/Sonia-Olea-Coontz.png\" alt=\"\" width=\"475\" height=\"289\" \/><p style=' padding: 0 4px 5px; margin: 0;'  class=\"wp-caption-text\">Sonia Olea Coontz had a stroke in 2011 that affected the movement of her right arm and leg. After modified stem cells were injected into her brain as part of a clinical trial, she says her limbs &#8220;woke up.&#8221; (credit: Mark Rightmire\/Stanford University School of Medicine)<\/p><\/div>\n<p>One of those patients, Sonia Olea Coontz, of Long Beach, California, now 36, had a stroke in May 2011. \u201cMy right arm wasn\u2019t working at all,\u201d said Coontz. \u201cIt felt like it was almost dead. My right leg worked, but not well.\u201d She walked with a noticeable limp. \u201cI used a wheelchair a lot. After my surgery, they woke up,\u201d she said of her limbs.<\/p>\n<p><strong>\u2018Clinically meaningful\u2019 results<\/strong><\/p>\n<p>The promising results set the stage for an expanded trial of the procedure now getting underway. They also call for new thinking regarding the permanence of brain damage, said\u00a0<a href=\"https:\/\/med.stanford.edu\/profiles\/gary-steinberg\" >Gary Steinberg<\/a>, MD, PhD, professor and chair of neurosurgery.<\/p>\n<p>\u201cThis was just a single trial, and a small one,\u201d cautioned Steinberg, who led the 18-patient trial and conducted 12 of the procedures himself. (The rest were performed at the University of Pittsburgh.) \u201cIt was designed primarily to test the procedure\u2019s safety. But patients improved by several standard measures, and their improvement was not only statistically significant, but clinically meaningful. Their ability to move around has recovered visibly. That\u2019s unprecedented. At six months out from a stroke, you don\u2019t expect to see any further recovery.\u201d<\/p>\n<p>The trial\u2019s results are detailed in a paper published online June 2 in\u00a0<em>Stroke<\/em>. Steinberg, who has more than 15 years\u2019 worth of experience in work with stem cell therapies for neurological indications, is the paper\u2019s lead and senior author.<\/p>\n<p>The procedure involved injecting\u00a0SB623 mesenchymal stem cells, derived from the bone marrow of two donors and then modified to beneficially alter the cells\u2019 ability to restore neurologic function.*<\/p>\n<p><strong>Motor-function improvements<\/strong><\/p>\n<p>Substantial improvements were seen in patients\u2019 scores on several widely accepted metrics of stroke recovery. Perhaps most notably, there was an overall 11.4-point improvement on the motor-function component of the Fugl-Meyer test, which specifically gauges patients\u2019 movement deficits. &#8220;Patients who were in wheelchairs are walking now,&#8221; said Steinberg, who is the Bernard and Ronni Lacroute-William Randolph Hearst Professor in Neurosurgery and Neurosciences.<\/p>\n<p>\u201cWe know these cells don\u2019t survive for more than a month or so in the brain,\u201d he added. \u201cYet we see that patients\u2019 recovery is sustained for greater than one year and, in some cases now, more than two years.\u201d<\/p>\n<p>Importantly, the stroke patients\u2019 postoperative improvement was independent of their age or their condition\u2019s severity at the onset of the trial. \u201cOlder people tend not to respond to treatment as well, but here we see 70-year-olds recovering substantially,\u201d Steinberg said. \u201cThis could revolutionize our concept of what happens after not only stroke, but traumatic brain injury and even neurodegenerative disorders. The notion was that once the brain is injured, it doesn\u2019t recover &#8212; you\u2019re stuck with it. But if we can figure out how to jump-start these damaged brain circuits, we can change the whole effect.<\/p>\n<p>\u201cWe thought those brain circuits were dead. And we\u2019ve learned that they\u2019re not.\u201d<\/p>\n<p><strong>New trial now recruiting 156 patients<\/strong><\/p>\n<p>A new randomized, double-blinded multicenter phase-2b trial aiming to enroll 156 chronic stroke patients is now actively recruiting patients. Steinberg is the principal investigator of that trial.\u00a0For more information, you can e-mail\u00a0<a href=\"mailto:stemcellstudy@stanford.edu\" >stemcellstudy@stanford.edu<\/a>. \u201cThere are close to 7 million chronic stroke patients in the United States,\u201d Steinberg said. \u201cIf this treatment really works for that huge population, it has great potential.\u201d<\/p>\n<p>Some 800,000 people suffer a stroke each year in the United States alone. About 85 percent of all strokes are ischemic: They occur when a clot forms in a blood vessel supplying blood to part of the brain, with subsequent intensive damage to the affected area. The specific loss of function incurred depends on exactly where within the brain the stroke occurs, and on its magnitude.<\/p>\n<p>Although approved therapies for ischemic stroke exist, to be effective they must be applied within a few hours of the event \u2014 a time frame that often is exceeded by the amount of time it takes for a stroke patient to arrive at a treatment center.<\/p>\n<p>Consequently, only a small fraction of patients benefit from treatment during the stroke\u2019s acute phase. The great majority of survivors end up with enduring disabilities. Some lost functionality often returns, but it\u2019s typically limited. And the prevailing consensus among neurologists is that virtually all recovery that\u2019s going to occur comes within the first six months after the stroke.<\/p>\n<p><em>* Mesenchymal stem cells are the naturally occurring precursors of muscle, fat, bone and tendon tissues. In preclinical studies, though, they\u2019ve not been found to cause problems by differentiating into unwanted tissues or forming tumors. Easily harvested from bone marrow, they appear to trigger no strong immune reaction in recipients even when they come from an unrelated donor. In fact, they may actively suppress the immune system. For this trial, unlike the great majority of transplantation procedures, the stem cell recipients received no immunosuppressant drugs.<\/em><\/p>\n<p><em>During the procedure, patients\u2019 heads were held in fixed positions while a hole was drilled through their skulls to allow for the injection of SB623 cells, accomplished with a syringe, into a number of spots at the periphery of the stroke-damaged area, which varied from patient to patient.<\/em><\/p>\n<p><em>Afterward, patients were monitored via blood tests, clinical evaluations and brain imaging. Interestingly, the implanted stem cells themselves do not appear to survive very long in the brain. Preclinical studies have shown that these cells begin to disappear about one month after the procedure and are gone by two months. Yet, patients showed significant recovery by a number of measures within a month\u2019s time, and they continued improving for several months afterward, sustaining these improvements at six and 12 months after surgery. Steinberg said it\u2019s likely that factors secreted by the mesenchymal cells during their early postoperative presence near the stroke site stimulates lasting regeneration or reactivation of nearby nervous tissue.<\/em><\/p>\n<p><em>No relevant blood abnormalities were observed. Some patients experienced transient nausea and vomiting, and 78 percent had temporary headaches related to the transplant procedure.<\/em><\/p>\n<hr \/>\n<p><strong>Abstract of\u00a0<em>Clinical Outcomes of Transplanted Modified Bone Marrow\u2013Derived Mesenchymal Stem Cells in Stroke: A Phase 1\/2a Study<\/em><\/strong><\/p>\n<p>Background and Purpose\u2014Preclinical data suggest that cell-based therapies have the potential to improve stroke outcomes.<\/p>\n<p>Methods\u2014Eighteen patients with stable, chronic stroke were enrolled in a 2-year, open-label, single-arm study to evaluate the safety and clinical outcomes of surgical transplantation of modified bone marrow\u2013derived mesenchymal stem cells (SB623).<\/p>\n<p>Results\u2014All patients in the safety population (N=18) experienced at least 1 treatment-emergent adverse event. Six patients experienced 6 serious treatment-emergent adverse events; 2 were probably or definitely related to surgical procedure; none were related to cell treatment. All serious treatment-emergent adverse events resolved without sequelae. There were no dose-limiting toxicities or deaths. Sixteen patients completed 12 months of follow-up at the time of this analysis. Significant improvement from baseline (mean) was reported for: (1) European Stroke Scale: mean increase 6.88 (95% confidence interval, 3.5\u201310.3;<em>P<\/em>&lt;0.001), (2) National Institutes of Health Stroke Scale: mean decrease 2.00 (95% confidence interval, \u22122.7 to \u22121.3;\u00a0<em>P<\/em>&lt;0.001), (3) Fugl-Meyer total score: mean increase 19.20 (95% confidence interval, 11.4\u201327.0;\u00a0<em>P<\/em>&lt;0.001), and (4) Fugl-Meyer motor function total score: mean increase 11.40 (95% confidence interval, 4.6\u201318.2;<em>P<\/em>&lt;0.001). No changes were observed in modified Rankin Scale. The area of magnetic resonance T2 fluid-attenuated inversion recovery signal change in the ipsilateral cortex 1 week after implantation significantly correlated with clinical improvement at 12 months (<em>P<\/em>&lt;0.001 for European Stroke Scale).<\/p>\n<p>Conclusions\u2014In this interim report, SB623 cells were safe and associated with improvement in clinical outcome end points at 12 months.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Injecting specially prepared human adult stem cells directly into the brains of chronic stroke patients proved safe and effective in restoring motor (muscle) function in a small clinical trial led by&nbsp;Stanford University School of Medicine&nbsp;investigators. The 18 patients had suffered their first and only stroke between six months and three years before receiving the injections, [&#8230;]<\/p>\n","protected":false},"author":13,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[42,49,43],"tags":[],"class_list":["post-8094","post","type-post","status-publish","format-standard","hentry","category-biotech","category-cognitive-scienceneuroscience","category-news"],"_links":{"self":[{"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/posts\/8094"}],"collection":[{"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/users\/13"}],"replies":[{"embeddable":true,"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/comments?post=8094"}],"version-history":[{"count":4,"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/posts\/8094\/revisions"}],"predecessor-version":[{"id":8125,"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/posts\/8094\/revisions\/8125"}],"wp:attachment":[{"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/media?parent=8094"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/categories?post=8094"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/tags?post=8094"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}