By: Katie Moisse, PhD
Although stem cell transplants might eventually represent an effective treatment for ALS, many challenges need to be overcome, such as how to deliver the cells into motor areas throughout the nervous system and, once they are in the right place, how to get their axons to connect to targets up to a metre away. The first FDA-approved clinical trial to assess the safety, not efficacy, of injecting stem cells into the nervous system of ALS patients started January 2010 at Emory University in Atlanta. However, research groups in Mexico and Germany are already touting their stem cell transplant protocols as treatments for ALS, promising patients positive results.
Because of the lack of effective treatments for ALS, patients are sometimes willing to try alternative and off-label treatments (such as unproven stem cell therapies) despite their risks, costs and unproven effects. In an effort to educate patients, an international group of ALS researchers created ALSUntangled to assess those treatments by analyzing the science supporting them and documenting patients? experiences with them. The team uses the social networking tools Twitter and NING to collect and review information and publishes its findings as open-access articles in the journal Amyotrophic Lateral Sclerosis.
In their latest reports, the ALSUntangled group led by Richard Bedlack, MD, PhD, director of Duke University Hospital?s ALS Clinic in Durham, North Carolina, revealed the results of their investigations into stem cell transplants at the Hospital San Jose Tecnologico de Monterrey in Mexico and the XCell Centre in Germany.
The Mexican group published the findings of their preliminary trial of stem cell transplants in ALS patients in the journal Cytotherapy in 2009. But the ALSUntangled group identified several flaws in the study. The rationale for the type of stem cells used (ones obtained from blood) and the site of injection (the frontal cortex of the brain) was vague. Bedlack and colleagues report it is unlikely that blood-derived stem cells could offer any neuroprotective effects. It is also unclear how injecting the cells, at various doses, into the frontal cortex could help preserve motor neuron function throughout the central nervous system, including the spinal cord. The patients selected for the treatment group, (not randomly assigned to it ? the normal practice for scientific trials), appeared to be progressing more slowly than those selected for the control group even before the transplant. In addition, neither patients nor researchers were blinded, failing to rule out any researcher bias or placebo effects.
The ALSUntangled group?s most worrisome finding with the Mexican clinic?s procedure concerned safety. The authors of the Cytotherapy study concluded that the transplant was a safe and well-tolerated procedure in ALS even though one patient out of 10 who received the stem cell injection died within 10 days after the procedure. The authors failed to provide adverse event tables (another normal practice for such studies), or perform any follow-up measures assessing whether the cells were even present when patients reached the end stage of the disease. The study also failed to assess cognitive function, which might be a concern following cortical injections.
Five patients from clinics overseen by ALSUntangled investigators had travelled to Mexico for stem cells at the time of the investigation, paying a minimum of $18,000 U.S. plus travel expenses for the procedure. Bedlack and colleagues concluded there is insufficient safety and efficacy data to support stem cell transplants at the Hospital San Jose Tecnologico de Monterrey.
Unlike the Mexican clinic, The XCell Centre ? a private stem cell clinic with locations in Dusseldorf and Cologne, Germany ? has not published any reports on the effects of its stem cell transplant procedure in ALS patients in a scientific journal. Rather, it advertises the treatment on its web site. The web site authors report having a Scientific and Medical Advisory Board of international experts, none of which are members of the ALS community of clinical scientists. And they market the same treatment to patients with ALS, Alzheimer's disease, autism, cardiovascular disease, cerebral palsy, diabetes mellitus types 1 and 2, failed back syndrome, macular degeneration, multiple sclerosis, osteoarthritis, Parkinson's disease, spinal cord injuries and stroke.
The XCell Centre transplant procedure begins with obtaining the patients? stem cells from a bone marrow biopsy. The following day, isolated stem cells are delivered back into the patients, but it is unclear whether the cells are injected into the bloodstream or the cerebrospinal fluid, according to the ALSUntangled group?s report. Patients are sent home one to three days later and some are contacted by the centre for a subjective report on how they are doing. The procedure costs 7,995 Euros (approximately $10,300) per injection.
More than 2,400 patients have undergone stem cell transplants at the XCell Centre since January 2007, according to the centre?s web site, but little data are reported. Similar to the Mexican clinic?s protocol, it is unclear whether the transplanted cells survive in ALS patients and whether functional measures, such as the ALS functional rating scale (ALS-FRS) scores, actually improve. Rather, it appears the centre contacted 53 ALS patients within six months after their transplants for a subjective progress report. Of these, 16 reported no positive changes, 17 reported ?perceived deterioration? and the remaining 20 reported some degree of improvement in some aspect of the disease, the details of which are unclear. However, none of the patients have personally described their experience with the treatment in the ?patient stories? section of the centre?s website.
At the time of the investigation, three patients from clinics overseen by ALSUntangled investigators had received treatments at the XCell Centre ? two worsened and one had no change in progression rate according to objective tests. The ALSUntangled group concluded that, in the absence of evidence that the transplanted cells are surviving and objective measures of patient responses, patients should not seek stem cell transplants at the XCell Centre.
The ALSUntangled group emphasizes that a randomized, blinded, controlled trial is the only way to assess the efficacy of stem cell transplants in ALS patients. Three patients enrolled in the Emory phase I trial to assess safety have had fetal stem cells (isolated from the spinal cord of an eight-week-old fetus) injected into their spinal cords, and a fourth patient is scheduled to receive cells at the end of May. No acute complications and no adverse effects have been reported.
ALSUntangled is dedicated to helping patients to ?fight smart, not just hard,? Bedlack says, by critically examining alternative and off-label therapies. The group has published four investigations and another has been submitted to the journal Amyotrophic Lateral Sclerosis. Their list of treatments to investigate, submitted by patients via Twitter, currently sits at 27.
Posted On: Monday, May 31, 2010
Modified: Monday, June 07, 2010
Category: ALS Research
Posted By: Andrew Romano
Although stem cell transplants might eventually represent an effective treatment for ALS, many challenges need to be overcome, such as how to deliver the cells into motor areas throughout the nervous system and, once they are in the right place, how to get their axons to connect to targets up to a metre away. The first FDA-approved clinical trial to assess the safety, not efficacy, of injecting stem cells into the nervous system of ALS patients started January 2010 at Emory University in Atlanta. However, research groups in Mexico and Germany are already touting their stem cell transplant protocols as treatments for ALS, promising patients positive results.
Because of the lack of effective treatments for ALS, patients are sometimes willing to try alternative and off-label treatments (such as unproven stem cell therapies) despite their risks, costs and unproven effects. In an effort to educate patients, an international group of ALS researchers created ALSUntangled to assess those treatments by analyzing the science supporting them and documenting patients? experiences with them. The team uses the social networking tools Twitter and NING to collect and review information and publishes its findings as open-access articles in the journal Amyotrophic Lateral Sclerosis.
In their latest reports, the ALSUntangled group led by Richard Bedlack, MD, PhD, director of Duke University Hospital?s ALS Clinic in Durham, North Carolina, revealed the results of their investigations into stem cell transplants at the Hospital San Jose Tecnologico de Monterrey in Mexico and the XCell Centre in Germany.
The Mexican group published the findings of their preliminary trial of stem cell transplants in ALS patients in the journal Cytotherapy in 2009. But the ALSUntangled group identified several flaws in the study. The rationale for the type of stem cells used (ones obtained from blood) and the site of injection (the frontal cortex of the brain) was vague. Bedlack and colleagues report it is unlikely that blood-derived stem cells could offer any neuroprotective effects. It is also unclear how injecting the cells, at various doses, into the frontal cortex could help preserve motor neuron function throughout the central nervous system, including the spinal cord. The patients selected for the treatment group, (not randomly assigned to it ? the normal practice for scientific trials), appeared to be progressing more slowly than those selected for the control group even before the transplant. In addition, neither patients nor researchers were blinded, failing to rule out any researcher bias or placebo effects.
The ALSUntangled group?s most worrisome finding with the Mexican clinic?s procedure concerned safety. The authors of the Cytotherapy study concluded that the transplant was a safe and well-tolerated procedure in ALS even though one patient out of 10 who received the stem cell injection died within 10 days after the procedure. The authors failed to provide adverse event tables (another normal practice for such studies), or perform any follow-up measures assessing whether the cells were even present when patients reached the end stage of the disease. The study also failed to assess cognitive function, which might be a concern following cortical injections.
Five patients from clinics overseen by ALSUntangled investigators had travelled to Mexico for stem cells at the time of the investigation, paying a minimum of $18,000 U.S. plus travel expenses for the procedure. Bedlack and colleagues concluded there is insufficient safety and efficacy data to support stem cell transplants at the Hospital San Jose Tecnologico de Monterrey.
Unlike the Mexican clinic, The XCell Centre ? a private stem cell clinic with locations in Dusseldorf and Cologne, Germany ? has not published any reports on the effects of its stem cell transplant procedure in ALS patients in a scientific journal. Rather, it advertises the treatment on its web site. The web site authors report having a Scientific and Medical Advisory Board of international experts, none of which are members of the ALS community of clinical scientists. And they market the same treatment to patients with ALS, Alzheimer's disease, autism, cardiovascular disease, cerebral palsy, diabetes mellitus types 1 and 2, failed back syndrome, macular degeneration, multiple sclerosis, osteoarthritis, Parkinson's disease, spinal cord injuries and stroke.
The XCell Centre transplant procedure begins with obtaining the patients? stem cells from a bone marrow biopsy. The following day, isolated stem cells are delivered back into the patients, but it is unclear whether the cells are injected into the bloodstream or the cerebrospinal fluid, according to the ALSUntangled group?s report. Patients are sent home one to three days later and some are contacted by the centre for a subjective report on how they are doing. The procedure costs 7,995 Euros (approximately $10,300) per injection.
More than 2,400 patients have undergone stem cell transplants at the XCell Centre since January 2007, according to the centre?s web site, but little data are reported. Similar to the Mexican clinic?s protocol, it is unclear whether the transplanted cells survive in ALS patients and whether functional measures, such as the ALS functional rating scale (ALS-FRS) scores, actually improve. Rather, it appears the centre contacted 53 ALS patients within six months after their transplants for a subjective progress report. Of these, 16 reported no positive changes, 17 reported ?perceived deterioration? and the remaining 20 reported some degree of improvement in some aspect of the disease, the details of which are unclear. However, none of the patients have personally described their experience with the treatment in the ?patient stories? section of the centre?s website.
At the time of the investigation, three patients from clinics overseen by ALSUntangled investigators had received treatments at the XCell Centre ? two worsened and one had no change in progression rate according to objective tests. The ALSUntangled group concluded that, in the absence of evidence that the transplanted cells are surviving and objective measures of patient responses, patients should not seek stem cell transplants at the XCell Centre.
The ALSUntangled group emphasizes that a randomized, blinded, controlled trial is the only way to assess the efficacy of stem cell transplants in ALS patients. Three patients enrolled in the Emory phase I trial to assess safety have had fetal stem cells (isolated from the spinal cord of an eight-week-old fetus) injected into their spinal cords, and a fourth patient is scheduled to receive cells at the end of May. No acute complications and no adverse effects have been reported.
ALSUntangled is dedicated to helping patients to ?fight smart, not just hard,? Bedlack says, by critically examining alternative and off-label therapies. The group has published four investigations and another has been submitted to the journal Amyotrophic Lateral Sclerosis. Their list of treatments to investigate, submitted by patients via Twitter, currently sits at 27.
Posted On: Monday, May 31, 2010
Modified: Monday, June 07, 2010
Category: ALS Research
Posted By: Andrew Romano