Intrastriatal CERE-120 (AAV-Neurturin) protects striatal and cortical neurons and delays motor deficits in a transgenic mouse model of Huntington's disease

Ramaswamy, Shilpa; McBride, Jodi L.; Han, Ina; Berry‐Kravis, Elizabeth; Zhou, Lili; Herzog, Christopher R.; Gasmi, Mehdi; Bartus, Raymond T.; Kordower, Jeffrey H.

doi:10.1016/j.nbd.2008.12.005

Cited by 54 publications

(29 citation statements)

References 28 publications

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“…Wild-type (B6C3F1/J) and Huntington’s disease (HD) (B6C3F1/J-TgN(HD82Gln)81Dbo(N171)) transgenic mice carrying a mutant Huntingtin gene were purchased from Jackson Labs and bred to produce litters for desensitization as previously described (Ramaswamy et al, 2009). Human fetal NPCs (hfNPC) (G010 cell line) were derived as neurospheres from early gestation cortex and fully characterized as previously described (McBride et al, 2004; Svendsen et al, 1998) and later expanded in vitro for three months using a three-dimensional adherent cell culture method (Wakeman et al, 2009).…”

Section: Methodsmentioning

confidence: 99%

Neonatal immune-tolerance in mice does not prevent xenograft rejection

Mattis

Wakeman

Tom

et al. 2014

Experimental Neurology

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Assessing the efficacy of human stem cell transplantation in rodent models is complicated by the significant immune rejection that occurs. Two recent reports have shown conflicting results using neonatal tolerance to xenografts in rats. Here we extend this approach to mice and assess whether neonatal tolerance can prevent the rapid rejection of xenografts. In three strains of neonatal immune-intact mice, using two different brain transplant regimes and three independent stem cell types, we conclusively show that there is rapid rejection of the implanted cells. We also address specific challenges associated with the generation of humanized mouse models of disease.

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Section: Methodsmentioning

confidence: 99%

Neonatal immune-tolerance in mice does not prevent xenograft rejection

Mattis

Wakeman

Tom

et al. 2014

Experimental Neurology

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“…Gene therapy approaches have shown promise for the treatment of Parkinson’s disease,[1-6] Alzheimer’s disease,[7,8] lysosomal storage diseases[9,10] and brain tumors. [11] Viral gene vectors have been used in clinical trials for neurological disorders and shown to be therapeutically effective.…”

mentioning

confidence: 99%

Targeted gene transfer to the brain via the delivery of brain-penetrating DNA nanoparticles with focused ultrasound

Mead

Mastorakos

Suk

et al. 2016

Journal of Controlled Release

133

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Gene therapy holds promise for the treatment of many pathologies of the central nervous system (CNS), including brain tumors and neurodegenerative diseases. However, the delivery of systemically administered gene carriers to the CNS is hindered by both the blood-brain barrier (BBB) and the nanoporous and electrostatically charged brain extracelluar matrix (ECM), which acts as a steric and adhesive barrier. We have previously shown that these physiological barriers may be overcome by, respectively, opening the BBB with MR image-guided focused ultrasound (FUS) and microbubbles and using highly compact “brain penetrating” nanoparticles (BPN) coated with a dense polyethylene glycol corona that prevents adhesion to ECM components. Here, we tested whether this combined approach could be utilized to deliver systemically administered DNA-bearing BPN (DNA-BPN) across the BBB and mediate localized, robust, and sustained transgene expression in the rat brain. Systemically administered DNA-BPN delivered through the BBB with FUS led to dose-dependent transgene expression only in the FUS-treated region that was evident as early as 24 h post administration and lasted for at least 28 days. In the FUS-treated region ~42% of all cells, including neurons and astrocytes, were transfected, while less than 6% were transfected in the contralateral non-FUS treated hemisphere. Importantly, this was achieved without any sign of toxicity or astrocyte activation. We conclude that the image-guided delivery of DNA-BPN with FUS and microbubbles constitutes a safe and non-invasive strategy for targeted gene therapy to the brain.

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“…Transgenic animal modeling of human diseases has led to biomedical breakthroughs that have significant impact on the diagnoses, treatments, and interventions in human diseases (Chan, 2004;Chan et al, 2001;Yang and Chan, 2011;Yang et al, 2008;Brosh et al, 2000;Cayzac et al, 2011;Hitz et al, 2009;Lassnig et al, 2005;Ramaswamy et al, 2009;Shavlakadze et al, 2005;Tsunematsu et al, 2011). Since the development of the first transgenic rodents in the early 1980s, thousands of transgenic rodents that captured conditions of human diseases have been developed.…”

Section: A Importance Of the Transgenic Nonhuman Primate Model Of Humentioning

confidence: 99%