Cell-based therapies for amyotrophic lateral sclerosis/motor neuron disease

Fadilah, S A W; Law, Zhe Kang; Lai, Nai Ming; Ismail, Nor Azimah; Ali, Raymond Azman

doi:10.1002/14651858.cd011742

Cited by 5 publications

(2 citation statements)

References 51 publications

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“…A recent Cochrane analysis of safety and efficacy data from phase I/II clinical stem cell‐based transplantation studies of neurological disorders revealed that the numbers of trials are still too low to warrant guidance for reliable clinical practice. This issue is of relevance when developing experimental therapies for diseases that are both lethal and incurable, such as ALS/motor neuron disease, for which standardization and reproducibility of treatments are emerging as critical but thorny issues.…”

Section: Discussionmentioning

confidence: 99%

Results from Phase I Clinical Trial with Intraspinal Injection of Neural Stem Cells in Amyotrophic Lateral Sclerosis: A Long-Term Outcome

Mazzini

Gelati

Profico

et al. 2019

Stem Cells Translational Medicine

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The main objective of this phase I trial was to assess the feasibility and safety of microtransplanting human neural stem cell (hNSC) lines into the spinal cord of patients with amyotrophic lateral sclerosis (ALS). Eighteen patients with a definite diagnosis of ALS received microinjections of hNSCs into the gray matter tracts of the lumbar or cervical spinal cord. Patients were monitored before and after transplantation by clinical, psychological, neuroradiological, and neurophysiological assessment. For up to 60 months after surgery, none of the patients manifested severe adverse effects or increased disease progression because of the treatment. Eleven patients died, and two underwent tracheotomy as a result of the natural history of the disease. We detected a transitory decrease in progression of ALS Functional Rating Scale Revised, starting within the first month after surgery and up to 4 months after transplantation. Our results show that transplantation of hNSC is a safe procedure that causes no major deleterious effects over the short or long term. This study is the first example of medical transplantation of a highly standardized cell drug product, which can be reproducibly and stably expanded ex vivo, comprising hNSC that are not immortalized, and are derived from the forebrain of the same two donors throughout this entire study as well as across future trials. Our experimental design provides benefits in terms of enhancing both intra‐ and interstudy reproducibility and homogeneity. Given the potential therapeutic effects of the hNSCs, our observations support undertaking future phase II clinical studies in which increased cell dosages are studied in larger cohorts of patients. stem cells translational medicine 2019;8:887&897

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Section: Discussionmentioning

confidence: 99%

Results from Phase I Clinical Trial with Intraspinal Injection of Neural Stem Cells in Amyotrophic Lateral Sclerosis: A Long-Term Outcome

Mazzini

Gelati

Profico

et al. 2019

Stem Cells Translational Medicine

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“…Other alternative treatments such as physical therapy may also provide some benefits to some of the clinical symptoms of patients with ALS, such as easing the pain, delaying the loss of strength, and preventing the complications. Additionally, although a few novel therapeutic strategies such as cell and gene therapy have been tested for the better treatment of ALS, there are still no definitive and conclusive outcome yet . Riluzole, the only drug approved by Food and Drug Administration (FDA) of United States, can moderately prolong ALS patients’ life span by 2‐3 months through the inhibition of the glutamate release, but it may only benefit a subset of patients with ALS .…”

Section: Introductionmentioning

confidence: 99%

n‐butylidenephthalide treatment prolongs life span and attenuates motor neuron loss in SOD1^G93A mouse model of amyotrophic lateral sclerosis

Zhou

Zhang

et al. 2017

CNS Neurosci Ther

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Cell-based therapies for amyotrophic lateral sclerosis/motor neuron disease

Fadilah

Law

Ismail

et al. 2016

Cochrane Database of Systematic Reviews

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Currently, there is a lack of high-quality evidence to guide practice on the use of cell-based therapy to treat ALS/MND.We need large, prospective RCTs to establish the efficacy of cellular therapy and to determine patient-, disease- and cell treatment-related factors that may influence the outcome of cell-based therapy. The major goals of future research should be to determine the appropriate cell source, phenotype, dose, and route of delivery, as these will be key elements in designing an optimal cell-based therapy programme for people with ALS/MND. Future research should also explore novel treatment strategies, including combinations of cellular therapy and standard or novel neuroprotective agents, to find the best possible approach to prevent or reverse the neurological deficit in ALS/MND, and to prolong survival in this debilitating and fatal condition.

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Cell-based therapies for amyotrophic lateral sclerosis/motor neuron disease

Cited by 5 publications

References 51 publications

Results from Phase I Clinical Trial with Intraspinal Injection of Neural Stem Cells in Amyotrophic Lateral Sclerosis: A Long-Term Outcome

Results from Phase I Clinical Trial with Intraspinal Injection of Neural Stem Cells in Amyotrophic Lateral Sclerosis: A Long-Term Outcome

n‐butylidenephthalide treatment prolongs life span and attenuates motor neuron loss in SOD1^G93A mouse model of amyotrophic lateral sclerosis

Cell-based therapies for amyotrophic lateral sclerosis/motor neuron disease

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Cell-based therapies for amyotrophic lateral sclerosis/motor neuron disease

Cited by 5 publications

References 51 publications

Results from Phase I Clinical Trial with Intraspinal Injection of Neural Stem Cells in Amyotrophic Lateral Sclerosis: A Long-Term Outcome

Results from Phase I Clinical Trial with Intraspinal Injection of Neural Stem Cells in Amyotrophic Lateral Sclerosis: A Long-Term Outcome

n‐butylidenephthalide treatment prolongs life span and attenuates motor neuron loss in SOD1G93A mouse model of amyotrophic lateral sclerosis

Cell-based therapies for amyotrophic lateral sclerosis/motor neuron disease

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n‐butylidenephthalide treatment prolongs life span and attenuates motor neuron loss in SOD1^G93A mouse model of amyotrophic lateral sclerosis