66 research outputs found
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Predicting the risk of disease in familial amyotrophic lateral sclerosis
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Preventing familial amyotrophic lateral sclerosis: Is a clinical trial feasible?
No full textComparison of Phenotypic Characteristics and Prognosis Between Black and White Patients in a Tertiary ALS Clinic
No full textA novel ALS SOD1 C6S mutation with implications for aggregation related toxicity and genetic counseling
No full textMaternally transmitted diabetes and deafness associated with a 10.4 kb mitochondrial DNA deletion
No full textLumbar Intraspinal Injection of Neural Stem Cells in Patients with Amyotrophic Lateral Sclerosis: Results of a Phase I Trial in 12 Patients
No full textAdvances in stem cell biology have generated intense interest in the prospect of transplanting stem cells into the nervous system for the treatment of neurodegenerative diseases. Here, we report the results of an ongoing phase I trial of intraspinal injections of fetal‐derived neural stems cells in patients with amyotrophic lateral sclerosis (ALS). This is a first‐in‐human clinical trial with the goal of assessing the safety and tolerability of the surgical procedure, the introduction of stem cells into the spinal cord, and the use of immunosuppressant drugs in this patient population. Twelve patients received either five unilateral or five bilateral (10 total) injections into the lumbar spinal cord at a dose of 100,000 cells per injection. All patients tolerated the treatment without any long‐term complications related to either the surgical procedure or the implantation of stem cells. Clinical assessments ranging from 6 to 18 months after transplantation demonstrated no evidence of acceleration of disease progression due to the intervention. One patient has shown improvement in his clinical status, although these data must be interpreted with caution since this trial was neither designed nor powered to measure treatment efficacy. These results allow us to report success in achieving the phase I goal of demonstrating safety of this therapeutic approach. Based on these positive results, we can now advance this trial by testing intraspinal injections into the cervical spinal cord, with the goal of protecting motor neuron pools affecting respiratory function, which may prolong life for patients with ALS. S TEM C ELLS 2012;30:1144–1151Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92063/1/1079_ftp.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/92063/2/SC_11-1235_sm_supplTable1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/92063/3/SC_11-1235_sm_supplFigure1.pd
Gut microbiome differences between amyotrophic lateral sclerosis patients and spouse controls
No full textObjective: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that is incurable and ultimately fatal. Few therapeutic options are available to patients. In this study, we explored differences in microbiome composition associated with ALS. Methods: We compared the gut microbiome and inflammatory marker profiles of ALS patients (n = 10) to those of their spouses (n = 10). Gut microbiome profiles were determined by 16S rRNA gene sequencing. Results: The gut microbial communities of the ALS patients were more diverse and were deficient in Prevotella spp. compared with those of their spouses. In contrast, healthy couples (n = 10 couples of the opposite sex) recruited from the same geographic region as the patient population did not exhibit these differences. Stool and plasma inflammatory markers were similar between ALS patients and their spouses. Predictive analysis of microbial enzymes revealed that ALS patients had decreased activity in several metabolic pathways, including carbon metabolism, butyrate metabolism, and systems involving histidine kinase and response regulators. Conclusions: ALS patients exhibit differences in their gut microbial communities compared with spouse controls. Our findings suggest that modifying the gut microbiome, such as via amelioration of Prevotella spp. deficiency, and/or altering butyrate metabolism may have translational value for ALS treatment
Intraspinal neural stem cell transplantation in amyotrophic lateral sclerosis: Phase 1 trial outcomes
No full textPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106747/1/ana24113.pd
Analysis of graft survival in a trial of stem cell transplant in ALS
No full textObjective The first US Food and Drug Administration–approved clinical trial to treat amyotrophic lateral sclerosis ( ALS ) with neural stem cell–based therapy is in progress. The goal of the current study was to identify and assess the survival of human spinal cord–derived neural stem cells ( HSSC s) transplanted into the spinal cord in patients with ALS . Methods Spinal cords transplanted with HSSCs were examined from six autopsy cases. Homogenized tissues were interrogated for the presence of donor versus recipient DNA using real‐time PCR methods ( qPCR ). Fluorescence in situ hybridization (FISH) was performed using DNA probes for XY chromosomes to identify male donor HSSCs in one female case, and immunohistochemistry (IHC) was used to characterize the identified donor cells. Results Genomic DNA from donor HSSC s was identified in all cases, comprising 0.67–5.4% of total tissue DNA in patients surviving 196 to 921 days after transplantation. In the one female patient a “nest” of cells identified on H&E staining were XY ‐positive by FISH , confirming donor origin. A subset of XY ‐positive cells labeled for the neuronal marker NeuN and stem cell marker SOX 2. Interpretation This is the first study to identify human neural stem cells transplanted into a human spinal cord. Transplanted HSSC s survived up to 2.5 years posttransplant. Some cells differentiated into neurons, while others maintained their stem cell phenotype. This work is a proof of concept of the survival and differentiation of human stems cell transplanted into the spinal cord of ALS patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109593/1/acn3134.pd
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