Experimental neurotransplantation treatment for hereditary cerebellar ataxias

Abstract

Hereditary cerebellar degenerations are a heterogeneous group of diseases often having a detrimental impact on patients’ quality of life. Unfortunately, no sufficiently effective causal therapy is available for human patients at present. There are several therapies that have been shown to affect the pathogenetic process and thereby to delay the progress of the disease in mouse models of cerebellar ataxias. The second experimental therapeutic approach for hereditary cerebellar ataxias is neurotransplantation. Grafted cells might provide an effect via delivery of a scarce neurotransmitter, substitution of lost cells if functionally integrated and rescue or trophic support of degenerating cells. The results of cerebellar transplantation research over the past 30 years are reviewed here and potential benefits and limitations of neurotransplantation therapy are discussed.

Therapeutic Potential of Mesenchymal Stem Cells vs. Estradiol Benzoate or Avosoya on the Cerebellar Cortex of Ovariectomized Adult Albino Rats

“…Cendelin [52] reported that various types of stem cells can be used for experimental neurotransplantation such as: embryonic or adult neural stem cells, embryonic stem cells, adult stem cells, mesenchymal stem cells isolated from various tissues. In a study of Chen et al [53], HUCBMCs were found to express BDNF and other factors such as NT-3 and GDNF.…”

Preventive motor training but not progenitor grafting ameliorates cerebellar ataxia and deregulated autophagy in tambaleante mice

“…Transplantation of distinct types of neural progenitors or stem cells has been broadly tested for replacement of degenerated PCs and/or rescue of functional deficits in several ataxia mouse models (for review, see Cendelin, 2016). Functional benefits were obtained after bilateral transplantation of foetal cerebellar cell suspension directly into the CN of adult pcd (Triarhou et al, 1996) or SCA1…”

Transplanted Human Neural Progenitor Cells Attenuate Motor Dysfunction and Lengthen Longevity in a Rat Model of Ataxia

“…Currently, negligible clinical alleviation of ataxic symptoms has been possible with a combination of physical therapy and drugs. Alternatively, the use of cell replacement therapy has shown notable promise to slow the progression of neuronal degeneration found in multiple neuronal disorders 3 . Cell replacement therapies for these disorders such as traumatic brain injury, Alzheimer’s, Parkinson’s, Huntington’s, amyloid lateral sclerosis, and, of importance to our study, ataxia are currently being investigated 4 , 5 .…”

“…Cell replacement therapies for these disorders such as traumatic brain injury, Alzheimer’s, Parkinson’s, Huntington’s, amyloid lateral sclerosis, and, of importance to our study, ataxia are currently being investigated 4 , 5 . Within treatments of ataxia, cerebellar Purkinje cells are usually the main target for cell replacement therapy 3 , 6 .…”

“…Numerous in vivo experiments have been conducted on the efficacy of reducing neurodegeneration via direct Purkinje cell replacement in ataxic rodent models 3 . Researchers found that injections of mesenchymal stem cells (MSCs) improved motor symptoms in the neurodegenerative Lurcher mice that exhibit progressive loss of Purkinje cells 7 , 8 .…”