Stem Cell Therapy Shows Evidence of Aiding Cognition, Lowering Amyloid Load in Mouse Model of Alzheimer’s

Stem Cell Therapy Shows Evidence of Aiding Cognition, Lowering Amyloid Load in Mouse Model of Alzheimer’s
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stem cell study

Neuralstem’s stem cell therapy for Alzheimer’s disease was found to improve cognition and lessen the load of amyloid-beta plaques in a mouse model of the disease, a study reports, recommending work continue into this possible Alzheimer’s treatment.

The therapy, called NSI-532.IGF1, combines human neural stem cells with IGF1, a factor that helps prevent degeneration of nerve cells.

The study, “Human neural stem cell transplantation improves cognition in a murine model of Alzheimer’s disease,” was published in the journal Scientific Reports.

“Alzheimer’s disease is a leading cause of dementia and there are currently no treatments available that significantly alter the course of this disease,” Eva Feldman, research director of the University of Michigan ALS Center of Excellence, and the study’s lead author said in a press release.

“We are encouraged by the results we have seen with human neural stem cells in this established animal model and look forward to continuing this collaboration with Neuralstem,” Feldman added.

Stem cells are undifferentiated, or naive, cells capable of giving rise to indefinitely more cells of the same type, and from which certain other types of cells can be produced by genetic differentiation.

Stem cell-based therapies for neurodegenerative diseases, like Alzheimer’s, are a potential alternative to single-target small molecules, as they provide a multifaceted approach to treating disease. Not only can they replace damaged tissue, they can also form synapses — the junctions between two nerve cells that allow them to communicate — modulate inflammation and potentiate the formation of neurons’ (nerve cells) natural niche. However, most are still in early testing.

Several preclinical studies have shown the short-term benefit of stem cell transplantation in murine models, with the therapy’s success linked to its stimulating effects in brain cells. The therapy in animals works to release signaling molecules, called neurotrophic factors, that help support nerve cell regeneration and provide a neuroprotective effect.

“This has supported a handful of ongoing clinical trials in AD [Alzheimer’s disease] patients assessing various mesenchymal stem cell types by intravenous and intraventricular [within the cerebrospinal fluid] delivery, and one completed open-label Phase I trial showing safe intracranial targeting of the hippocampus [ NCT01297218 and NCT01696591],” the researchers wrote.

Neuralstem has developed a human neural stem cell line safely engineered to produce multiple neurotrophic factors.

The company has obtained investigational new drug status for NSI-566RSC, a spinal cord-derived cell line that is being evaluated in a clinical trial in amyotrophic lateral sclerosis (ALS) patients.

In a previous study, researchers showed that Neuralstem’s human neural stem cell line was successfully transplanted into the corpus callosum — a group of nerve fibers bridging the left and right sides of the brain — of a mouse model of Alzheimer’s disease.

The Michigan researchers transplanted NSI-532.IGF1 cells into the intracranial region of the brain in a mouse model of Alzheimer’s, the APP/PS1 model, engineered to carry mutations in genes linked with Alzheimer’s in humans.

Specifically, they planted the cells in a region called fimbria fornix, which is part of the hippocampus — a key structure in the brain critical for memory formation.

Four weeks later, the researchers assessed animals’ cognitive performance using an object recognition test, which evaluates hippocampus-dependent short-term memory.

Compared to sham-control mice (submitted to surgery but not receiving any stem cell transplant), animals given NSI-532.IGF1 spent significantly more time exploring the novel object, a standard behavior also observed in healthy mice (wild-type controls). This suggested that neural stem cell transplant improved short-term non-associative memory in these animals.

At 16-weeks following transplantation, researchers used the Morris water maze test — which evaluates spatial memory and learning — and reported that NSI-532.IGF1 transplanted animals performed significantly better than sham-control mice.

Cognitive improvements in stem cell-transplanted mice were paralleled by a significantly reduction in the number of amyloid-beta toxic plaques, a hallmark of Alzheimer’s disease. Transplanted animals also showed an activation of microglia, the brain’s resident immune cells, that may help clear the toxic amyloid-beta aggregates.

The transplanted stem cells, however, had no effect on proteins linked to synaptic formation.

“NSI-532.IGF1 is a second-generation cell therapy candidate that is engineered to combine neural stem cells with a neuroprotective protein, IGF-1, thereby targeting neurodegenerative conditions like AD,” said Karl Johe, PhD, chief scientific officer at Neuralstem. “This preclinical study from Dr. Feldman’s team suggests that the combined properties of neural stem cells and IGF-1 may mitigate the pathology and cognitive deficits associated with Alzheimer’s disease.”

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