Gene therapy for Huntington's disease

Ramaswamy, Shilpa; Kordower, Jeffrey H.

doi:10.1016/j.nbd.2011.12.030

Cited by 52 publications

(27 citation statements)

References 175 publications

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“…In the last few years, gene therapies for neurologic diseases are being intensively studied in neuromuscular disorders and Huntington disease. [16][17][18][19] Therapies using antisense oligonucleotides are being specifically developed for diseases with known dominant negative mutations. In the field of epilepsy, we are still lagging behind in targeted gene therapy development, and it is time to make the mental shift when we think about developing novel epilepsy therapies.…”

Section: Resultsmentioning

confidence: 99%

Extending the KCNQ2 encephalopathy spectrum

Weckhuysen¹,

Ivanović²,

Hendrickx³

et al. 2013

Neurology

200

283

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Section: Resultsmentioning

confidence: 99%

Extending the KCNQ2 encephalopathy spectrum

Weckhuysen¹,

Ivanović²,

Hendrickx³

et al. 2013

Neurology

200

283

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“…One possible avenue for HD treatment involves gene therapy to prevent production of the mutant protein, typically using either anti-sense DNA oligonucleotides (ASOs) against mutant huntingtin mRNA, or RNA that interferes with huntingtin expression (RNAi) (Crook and Housman, 2013; Ramaswamy and Kordower, 2012). Several studies have shown that direct delivery of RNAi molecules to the forebrain via an AAV vehicle can reduce mutant Htt production and slow phenotypic progression in mouse HD models (DiFiglia et al, 2007; Wang et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Effect of early embryonic deletion of huntingtin from pyramidal neurons on the development and long-term survival of neurons in cerebral cortex and striatum

Dragatsis

Dietrich

Ren

et al. 2018

Neurobiology of Disease

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We evaluated the impact of early embryonic deletion of huntingtin (htt) from pyramidal neurons on cortical development, cortical neuron survival and motor behavior, using a cre-loxP strategy to inactivate the mouse htt gene (Hdh) in emx1-expressing cell lineages. Western blot confirmed substantial htt reduction in cerebral cortex of these Emx-httKO mice, with residual cortical htt in all likelihood restricted to cortical interneurons of the subpallial lineage and/or vascular endothelial cells. Despite the loss of htt early in development, cortical lamination was normal, as revealed by layer-specific markers. Cortical volume and neuron abundance were, however, significantly less than normal, and cortical neurons showed reduced brain-derived neurotrophic factor (BDNF) expression and reduced activation of BDNF signaling pathways. Nonetheless, cortical volume and neuron abundance did not show progressive age-related decline in Emx-httKO mice out to 24 months. Although striatal neurochemistry was normal, reductions in striatal volume and neuron abundance were seen in Emx-httKO mice, which were again not progressive. Weight maintenance was normal in Emx-httKO mice, but a slight rotarod deficit and persistent hyperactivity were observed throughout the lifespan. Our results show that embryonic deletion of htt from developing pallium does not substantially alter migration of cortical neurons to their correct laminar destinations, but does yield reduced cortical and striatal size and neuron numbers. The Emx-httKO mice were persistently hyperactive, possibly due to defects in corticostriatal development. Importantly, deletion of htt from cortical pyramidal neurons did not yield age-related progressive cortical or striatal pathology.

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“…As previously mentioned, preventing BBB breakdown might also have a positive effect on Aβ accumulation (Deane et al, 2008; Bell and Zlokovic, 2009). Even if research on these new therapeutic approaches is not yet accessible in humans, their potential therapeutic implications have already created enthusiasm in the scientific community (Bu, 2009; Ramaswamy and Kordower, 2011; Mahley and Huang, 2012a). …”

Section: Treatmentmentioning

confidence: 99%

The potential applications of Apolipoprotein E in personalized medicine

Villeneuve

Brisson

Marchant

et al. 2014

Front. Aging Neurosci.

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Personalized medicine uses various individual characteristics to guide medical decisions. Apolipoprotein (ApoE), the most studied polymorphism in humans, has been associated with several diseases. The purpose of this review is to elucidate the potential role of ApoE polymorphisms in personalized medicine, with a specific focus on neurodegenerative diseases, by giving an overview of its influence on disease risk assessment, diagnosis, prognosis, and therapy. This review is not a systematic inventory of the literature, but rather a summary and discussion of novel, influential and promising works in the field of ApoE research that could be valuable for personalized medicine. Empirical evidence suggests that ApoE genotype informs pre-symptomatic risk for a wide variety of diseases, is valuable for the diagnosis of type III dysbetalipoproteinemia, increases risk of dementia in neurodegenerative diseases, and is associated with a poor prognosis following acute brain damage. ApoE status appears to influence the efficacy of certain drugs, outcome of clinical trials, and might also give insight into disease prevention. Assessing ApoE genotype might therefore help to guide medical decisions in clinical practice.

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Gene therapy for Huntington's disease

Cited by 52 publications

References 175 publications

Extending the KCNQ2 encephalopathy spectrum

Extending the KCNQ2 encephalopathy spectrum

Effect of early embryonic deletion of huntingtin from pyramidal neurons on the development and long-term survival of neurons in cerebral cortex and striatum

The potential applications of Apolipoprotein E in personalized medicine

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