Developing Stem Cell Therapies for Juvenile and Adult-Onset Huntington's Disease

Abstract

Stem cell therapies have been explored as a new avenue for the treatment of neurologic disease and damage within the CNS in part due to their native ability to mimic repair mechanisms in the brain. Mesenchymal stem cells have been of particular clinical interest due to their ability to release beneficial neurotrophic factors and their ability to foster a neuroprotective microenviroment. While early stem cell transplantation therapies have been fraught with technical and political concerns as well as limited clinical benefits, mesenchymal stem cell therapies have been shown to be clinically beneficial and derivable from nonembryonic, adult sources. The focus of this review will be on emerging and extant stem cell therapies for juvenile and adult-onset Huntington's disease.

Commonalities in Biological Pathways, Genetics, and Cellular Mechanism between Alzheimer Disease and Other Neurodegenerative Diseases: An In Silico-Updated Overview

“…The pathophysiology of HD is linked to an 'expanded trinucleotide repeat' (CAG) in the IT-15 gene on chromosome 4 [41]. Current treatments for HD are unable to delay the progression and onset of the disease [42]. …”

Engineered BDNF producing cells as a potential treatment for neurologic disease

“…Following transplantation, treated mice displayed significantly less anxiety-like behaviors than untreated transgenic mice. These results, along with the abundance of peer-reviewed articles (see [98]) provide compelling evidence for the proposed use of genetically engineered MSC as a candidate therapy for changing the trajectory of disease progression in patients diagnosed with early-stage HD.…”

“…[98] MSCs have been shown to be readily engineered using viral vectors to robustly deliver growth factors. [99,100] Using gene-modified MSCs as a delivery strategy addresses certain safety concerns involved with the direct use of viral vectors, as MSCs do not permanently engraft into host tissues.…”

“…noggin). Unlike direct BDNF delivery via viral vector injection or recombinant protein administration into the brain, MSCs migrate into areas of tissue damage and have been shown to have numerous tissue healing effects (reviewed in [98]). Studies have shown that MSCs do not permanently engraft into host tissues; however, the duration and strategic localization of BDNF production should be adequate to produce a beneficial effect that will outlast the survival of MSCs.…”

The Transcription Factor XBP1 in Memory and Cognition: implications in Alzheimer’s Disease

“…For instance, use of AAV in the clinic has proven difficult due to host immunogenicity to the virus and limited biodistribution (197,198). More recent approaches utilizing human mesenchymal stem cells (MSCs) that have been genetically engineered to produce BDNF have shown beneficial outcomes in a Huntington disease model (199). Importantly, some pharmaceutical companies, namely Atherys, SanBio and Brain Storm Therapeutics, finalized several MSC therapy-based phase II clinical trials involving ischemic stroke and amyotrophic lateral sclerosis patients and reported no adverse effects whatsoever (200).…”