Developing stem cell therapies for juvenile and adult-onset Huntington's disease

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From: Regenerative Medicine(Vol. 10, Issue 5)
Publisher: Future Medicine Ltd.
Document Type: Report
Length: 14,836 words
Lexile Measure: 2110L

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Author(s): Kyle D Fink aff1 , Peter Deng aff1 , Audrey Torrest aff1 , Heather Stewart aff1 , Kari Pollock aff1 , William Gruenloh aff1 , Geralyn Annett aff1 , Teresa Tempkin aff2 , Vicki Wheelock aff3 , Jan A Nolta [*] aff1


Huntington's disease; regenerative medicine; stem cell; transplantation

Significant advances in stem cell therapies

The clinical use of stem cell therapies has gained approval for a variety of injuries and diseases of the CNS. While much work is still needed before the widespread use of stem cells in a clinical setting can be realized, this mode of therapy may be advantageous to treat neurological disorders than many others because of the ability of stem cells to accurately mimic the normal cell repair and development process in the brain [1 ]. Although cell transplantation therapies have been fraught with technical and political problems, there are signs that this approach has considerable potential. Early work with Parkinson's disease, where the first clinical trials were performed in the mid-1980s and a total of 300-400 patients have been treated subsequently with fetal cell transplantation and in the open label studies, has yielded evidence of some functional improvement [for review [2,3 ]] as measured by withdrawal of anti-parkinsonian medications. Patients with Huntington's disease (HD) have received clinical benefits from implants of fetal/embryonic stem cells as well, however, these effects have been shown to be temporal [4-6 ].

Another type of cells, mesenchymal stem cells (MSCs), have emerged for clinical transplantation studies due to their capacity to release neurotrophic factors and their ability to create a neuroprotective microenvironment through the release of specific ILs and cytokines. Clinical trials using MSCs in the CNS are now also underway, and are focused on the safety of the cells. MSCs have been autologously transplanted into the subventricular zone in patients with advanced Parkinson's disease [ 7 ], intravenously in patients that had suffered a stroke [8,9 ], and umbilical cord MSCs have been administered intravenously in children with cerebral palsy [10 ] with no adverse side effects from the cells and observed clinical efficacy as measured by improvements in neurological domains and fractional anisotropy values in brain MRI-DTI.

Stem cell clinical trials for stroke, spinal cord injury and amyotrophic lateral sclerosis are already underway while additional studies utilizing adult stem cells are nearing clinical trials for Parkinson's and Alzheimer's and HD.

The goal of stem cell transplantation should focus on providing therapeutic benefit through two main mechanisms. Successful cell transplantation should be able to work synergistically with the endogenous microenvironment to upregulate intrinsic cell proliferation or neuroprotection via trophic factor secretion and immune modulation, potentially enhancing the overall regenerative capacity of the transplanted tissue [11 ], or by being capable of integrating into the endogenous host network and replacing or repairing the lost neurons. This review will focus on the potential of adult stem cells to provide neuroprotection and immune modulation in adult-onset and juvenile HD.

Huntington's disease

HD is an autosomal-dominant disorder caused by an expanded and unstable CAG trinucleotide repeat that causes a progressive degeneration...

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Gale Document Number: GALE|A424015186