In this webinar we explore developing in vitro models for your rare disease research – from both a patient group and industry perspective. Over the course of the 60-minute session our speakers discuss the following topics:

• 
What makes a good in vitro model
• The pros and cons of in vitro model system types
• The use of stem cell-derived models to measure the effectiveness of compounds
• How to initiate collaborations for reprogramming and modelling diseases using stem cells

Expert speakers include:

• Geraldine Bliss, President and Co-founder at CureSHANK
• Dr Tuzer Kalkan, Principal Scientist at Bit Bio
• Dr Mariangela Iovino, Group Leader, Biology at Charles River Laboratories
• Dr Phil Brownjohn, Senior Scientist, Pharmacologist at Healx

You can watch the webinar recording below. We did our best to answer as many questions during the session, but if you have any additional ones for us please take a look at our FAQs section or submit them via email to accelerate@healx.ai

Webinar | How to Develop In Vitro Models for Rare Disease Research from Healx on Vimeo.

About our speakers

Geraldine Bliss | President and Co-founder at CureSHANK

Geraldine’s son, Charles, has Phelan-McDermid Syndrome, caused by a partial deletion of the SHANK3 gene. His severe form of epilepsy, Lennox Gastaut Syndrome, has had a devastating impact. CureSHANK was born from her promise to Charles to help him get better.

Dr Tuzer Kalkan | Principal Scientist at Bit Bio

Tuzer completed her PhD at State University of New York with Professor Gerald Thomsen, investigating the role of TGF-beta pathway in Xenopus neural crest formation. For her postdoc, she moved to the Cambridge Stem Cell Institute to investigate molecular mechanisms that regulate self-renewal of pluripotent stem cells and their early transitions towards lineage differentiation, with a focus on transcription factors and chromatin regulation. At Bit Bio, Tüzer is leading a project to reprogram pluripotent stem cells to develop models for tox screening.

Dr Mariangela Iovino | Group Leader, Biology at Charles River Laboratories

Mariangela graduated from University of Naples (Naples, Italy) with a degree in medical biotechnology. She went on to complete her PhD in molecular and cellular biology as part of a joint programme between Merck (Rome, Italy), University of Perugia and University of Cambridge (UK). Mariangela was also awarded a master’s degree in medical sciences from the University of Cambridge and continued her career in Cambridge as a postdoctoral researcher in the Department of Clinical Neuroscience, where she gained extensive experience in stem cell culture and neuronal differentiation. Mariangela joined Charles River in 2013 and she is currently a Group Leader in the biology department where she established novel assays using patient-derived human embryonic and induced pluripotent stem cells.

Dr Phil Brownjohn | Senior Scientist, Pharmacologist at Healx

As a pharmacologist at Healx, Phil is responsible for developing a pharmacological rationale for repurposing candidates predicted by the Healnet platform, and leading their preclinical validation through to the clinical testing phase. Prior to his role at Healx, Phil held two postdoctoral positions, including five years at the University of Cambridge using stem cell-derived neuronal models to understand the molecular basis of neurodegenerative disease and screen for disease-modifying drugs. Phil obtained an honours degree and PhD in Pharmacology and Toxicology from the University of Otago, New Zealand.

Q&A with the panelists

We received so many great questions during the webinar that we didn’t have time to answer all of them! Please take a look below for the answers to the questions we didn’t have chance to cover on the day. And for a recap of all other questions addressed during the Q&A session, please watch from 00:51:24 on the webinar recording.

Q. Geraldine, it’s remarkable how you’ve generated a biobank for shankopathies. Have the cells been used for research into these disorders yet? If so how?

Geraldine Bliss (CureSHANK): Yes, the cells have been used for research on Phelan-McDermid syndrome. The first research team (Ricardo Dolmetsch and his post-doc, Alex Shcheglovitov) characterized PMS neurons and did some drug-screening on them and found that IGF-1 restored synaptic deficits in the neurons. IGF-1 is in clinical trial for PMS.

When Dr Shcheglovitov completed his post-doc, he secured a position at The University of Utah, where he continues to work on PMS neurons and brain organoids (like mini-brains). At least one other team has accessed the cell lines to grow and characterise neurons. Another research team has accessed them for the purpose of generating enteric neurons to study the mechanisms of gut dysfunction in PMS and autism.

Q. Dr Kalkan you mentioned reprogramming and optiox. What is the connection between the two? Do you have disease models for dementia?

Dr Tuzer Kalkan (BitBio): Human induced pluripotent stem cells (iPSCs) provide an excellent source of starting material to generate reliable human cell models. But stem cell differentiation using classical differentiation methods is challenging, fraught with inconsistency and complex protocols that are difficult to reproduce and scale. Reprogramming cells by directly activating the program that defines a particular cellular identity is able to shorten the time frames of manufacture compared to classical differentiation. As a result, stem cells convert directly into any desired cell type, such as those of the liver, brain or immune system. However, until recently reprogramming of cells including iPSCs has been hampered by low efficacy and yields.

By applying a cellular reprogramming approach supported by a uniquely-engineered genetic switch, opti-ox (optimised inducible over-expression), Bit Bio is able to overcome gene silencing and with it the restrictions of inefficient cellular reprogramming. Its application to cell reprogramming enables precisely controlled expression of transcription factors and results in deterministic reprogramming of entire human iPSC cultures. The resulting mature human iPSC-derived cells are functional within days, and provide high quality cellular models with simple protocols. Cells are scalable, consistent and easy to use, and provide robust human cell models for high throughput screening and disease modelling.

Bit Bio human iPSC-derived functional glutamatergic neurons, the ioNEURONS/glut, provide a high quality human model for the study of neurological activity and disease. Bit Bio is launching iPSC-derived oligodendrocytes and GABAergic neurons later this year, and disease-specific CNS cell types for Frontotemporal Dementia, Huntington’s disease and Parkinson’s disease. If you would like more information please get in touch at info@bit.bio