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May 2015

Komatsu M, Wheeler HE, Chung S, Low SK, Wing C, Delaney SM, Gorsic LK, Takahashi A, Kubo M, Kroetz DL, Zhang W, Nakamura Y, Dolan ME

Pharmacoethnicity in Paclitaxel-Induced Sensory Peripheral Neuropathy

Clin Cancer Res [Epub ahead of print]

Publication Date: May 26, 2015

Product Type: iCell GABANeurons

Summary:

iCell Neurons in combination with clinical GWAS studies for chemotherapy-induced peripheral neuropathies (CIPN) were used to identify the most promising genetic variants and genes associated with CIPN underlying ethnic specificity. iCell Neurons were used to validate gene function through the use of gene knockdown by siRNA transfection and neurite outgrowth assessment.

Impact:

iCell Neurons offer a relevant in vitro cell model to assist with the elucidation of variants specific to the Asian population that may be helpful in developing personalized cancer treatments.

April 2015

Pellett S, Tepp WH, Scherf JM, Pier, CL and Johnson EA

Activity of Botulinum Neurotoxin Type D (Strain 1873) in Human Neurons

Toxicon. 101: 63 - 9

Publication Date: April 30, 2015

Product Type: iCell GABANeurons

Summary:

iCell Neurons were used to examine BoNT/D activity, a lesser known BoNT derivative, in human cells. The results showed that BoNT/D can enter and cleave VAMP 2 but at a significantly lower efficiency and shorter duration of action than BoNT/A1, the common serotype used in the cosmetic industry and to a lesser degree as a therapeutic.

Impact:

This study supports the need to explore other serotypes, besides the more well-known types, that could be considered a potential bioterrorism attack and for potential use as a novel therapeutic or drug delivery method. iCell Neurons are a relevant human model to detect BoNT and further characterize its properties.

Chatzidaki A, Fouillet A, Li J, Dage J, Millar NS, Sher E, Ursu D

Pharmacological Characterisation of Nicotinic Acetylcholine Receptors Expressed in Human iPSC-Derived Neurons

PLoS One 10(4):e0125116

Publication Date: April 23, 2015

Product Type: iCell GABANeurons

Summary:

iCell Neurons were used to examine the expression and functional properties of nicotinic acetylcholine receptors (nAChRs). Gene expression analysis indicated the presence of transcripts encoding several nAChR subunits, α3-α7, β1, β2, and β4 subunits. In addition, similarly high transcript levels were detected for the truncated dupα7 subunit transcript, encoded by the partially duplicated gene CHRFAM7A, which has been associated with psychiatric disorders such as schizophrenia.

Impact:

Neuronal nAChRs have been implicated in a variety of neurological and psychiatric disorders, including Alzheimer’s disease, schizophrenia, depression and ADHD, thus drawing considerable interest, from both academia and pharma, in developing novel cellular assays. These cells therefore represent a great tool to advance the understanding of the properties of native human nAChRs.

February 2015

Diouf B, Crews KR, Lew G, Pei D, Cheng C, Bao J, Zheng JJ, Yang W, Fan Y, Wheeler HE, Wing C, Delaney SM, Komatsu M, Paugh SW, McCorkle JR, Lu X, Winick NJ, Carroll WL, Loh ML, Hunger SP, Devidas M, Pui CH, Dolan ME, Relling MV, Evans WE

Association of an Inherited Genetic Variant with Vincristine-related Peripheral Neuropathy in Children with Acute Lymphoblastic Leukemia

JAMA 313(8):815-23

Publication Date: February 24, 2015

Product Type: iCell GABANeurons

Summary:

 iCell Neurons were used to assess chemotherapeutic (vincristine)-induced toxicity and the relationship between CEP72 expression and the degree of patient sensitivity to vincristine. These data corroborate their clinical finding that an inherited polymorphism in CEP72 is associated with an increased risk and severity of vincristine-related peripheral neuropathy.

Impact:

iCell Neurons confirmed clinical findings of a genetic link to the risk and severity of chemotherapeutic-induced neuropathy. These findings may provide basis for safer dosing of the widely used anticancer agent vincristine.