Robin J. Kleiman

A community-led initiative to de-risk and advance Parkinson’s disease therapeutic targets

Jonathan Behr, Ryan Birol, Cornelis Blauwendraat, Bradford H. Casey et autres

Identifying effective therapeutic targets for Parkinson's disease (PD) is challenging, with no current disease-modifying therapies available. To address this, The Michael J. Fox Foundation for Parkinson's Research launched the Targets to Therapies (T2T) initiative, uniting experts to prioritize and validate promising targets. …

us, gb, be, Kenya, cn, it (code pays fourni par la source)

Cis-regulatory elements driving motor neuron-selective viral payload expression within the mammalian spinal cord

M. Aurel Nagy, Spencer T. Price, Kristina Wang, Stanley Gill et autres

Spinal motor neuron (MN) dysfunction is the cause of a number of clinically significant movement disorders. Despite the recent approval of gene therapeutics targeting these MN-related disorders, there are no viral delivery mechanisms that achieve MN-restricted transgene expression. In this study, chromatin …

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Cis-regulatory elements driving motor neuron-restricted viral payload expression within the mammalian spinal cord

M. Aurel Nagy, Spencer T. Price, Kristina Wang, Stanley P Gill et autres

Spinal motor neuron (MN) dysfunction is the cause of a number of clinically significant movement disorders. Despite the recent approval of gene therapeutics targeting these MN-related disorders, there are no viral delivery mechanisms that achieve MN-restricted transgene expression. In this study, chromatin …

us (code pays fourni par la source)

16p13.11 deletion variants associated with neuropsychiatric disorders cause morphological and synaptic changes in induced pluripotent stem cell-derived neurons

Elizabeth D. Buttermore, Nickesha Camille Anderson, Pin-Fang Chen, Nina R. Makhortova et autres

16p13.11 copy number variants (CNVs) have been associated with autism, schizophrenia, psychosis, intellectual disability, and epilepsy. The majority of 16p13.11 deletions or duplications occur within three well-defined intervals, and despite growing knowledge of the functions of individual genes within these intervals, the …

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Contributors

Irene Antony, Elizabeth D. Buttermore, Gerarda Cappuccio, Juan Cruz Casabona et autres

Developing clinically translatable screens using iPSC-derived neural cells

Sandra J. Engle, Patrick W. Faloon, Abigail Mariga, Robin J. Kleiman

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Gene-based therapeutics for rare genetic neurodevelopmental psychiatric disorders

Beverly L. Davidson, Guangping Gao, Elizabeth Berry‐Kravis, Allison M. Bradbury et autres

We are in an emerging era of gene-based therapeutics with significant promise for rare genetic disorders. The potential is particularly significant for genetic central nervous system disorders that have begun to achieve Food and Drug Administration approval for select patient populations. This …

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Human inducible pluripotent stem cells: Realization of initial promise in drug discovery

Robin J. Kleiman, Sandra J. Engle

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Generation and characterization of human induced pluripotent stem cells (iPSCs) from three male and three female patients with CDKL5 Deficiency Disorder (CDD)

Pin-Fang Chen, Teresa C. Chen, Taylor E. Forman, Amanda Cantu Swanson et autres

CDKL5 Deficiency Disorder (CDD) is a rare X-linked monogenic developmental encephalopathy that is estimated to affect 1:42,000 live births. CDD is caused by pathogenic variants in the CDKL5 gene and is observed in both male and female patients. Here, we report the …

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Phenotypic Screen with TSC-Deficient Neurons Reveals Heat-Shock Machinery as a Druggable Pathway for mTORC1 and Reduced Cilia

Alessia Di Nardo, Isadora Lenoël, Kellen Diamond Winden, Alina Rühmkorf et autres

Tuberous sclerosis complex (TSC) is a neurogenetic disorder that leads to elevated mechanistic targeting of rapamycin complex 1 (mTORC1) activity. Cilia can be affected by mTORC1 signaling, and ciliary deficits are associated with neurodevelopmental disorders. Here, we examine whether neuronal cilia are …

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How to develop therapeutic and translational research collaborations with industry

Robin J. Kleiman, Michael Ehlers

Discovery and development of new medicines requires the talent and passion of both academic and industrial scientists. Identifying the optimal set of circumstances for direct collaboration between academic and industry teams requires a mutual understanding of what each partner brings to the …

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A High-Content Screen Identifies TPP1 and Aurora B as Regulators of Axonal Mitochondrial Transport

Evgeny Shlevkov, Himanish Basu, Mark‐Anthony Bray, Zheng Sun et autres

Dysregulated axonal trafficking of mitochondria is linked to neurodegenerative disorders. We report a high-content screen for small-molecule regulators of the axonal transport of mitochondria. Six compounds enhanced mitochondrial transport in the sub-micromolar range, acting via three cellular targets: F-actin, Tripeptidyl peptidase 1 …

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