CURRENT WINNER

MACARTHUR FELLOWS PROGRAM

Lorenz Studer

Stem Cell Biologist | Class of 2015

https://www.macfound.org/fellows/947/

118 publications on PubMed

https://www.ncbi.nlm.nih.gov/pubmed/?term=LORENZ+STUDER

PRESIDING

Dagmar Ringe Professor of Biochemistry, Chemistry and Rosenstiel Basic Medical Sciences Research Center

WELCOME

Lisa Lynch Provost and Maurice B. Hexter Professor of Social and Economic Policy Brandeis University

RESPONSE Lorenz Studer, MD Director, Center for Stem Cell Biology Memorial Sloan Kettering Cancer Center Member, Developmental Biology Program Memorial Sloan Kettering Cancer Center

Fully defined protocol for all ectodermal lineage

• Nervous system: Forebrain, Midbrain, Spinal cord:
• CNS lineage to PNS Lineage
• Excitatory cortical neurons
• cortical interneurons Astrocytes
• microglia
• Age-reset disease – late-onset during reprogramming – Is age reversible?
• Loss of age-related markers
• iPSC-derived cells yield stage cell upon differentiation
• In vitro differentiation techniques: 2D Directed Differentiation 3D- Organoids
• Graded MORPHOGEN SIGNALING
• DOXYCYLINE: ISHH-ORGANIZER – 5 discrete forebrain regions
• Building Human brain cells in 2D and in 3D
• Organized cells –>>>  directed organoids –>> Organized Organoids
• Parkinson, 1817 – Essay on Shaky Palsy (Niagrostaterial pathway)
• Genetics and related dysfunction: affecting PD
• Charckot, 1889
• PD – new approach following drugs and deep brain stimulation failure in advanced disease: Fetal tissue transplant trials: Fetal Grafting
• graft-induced dyskinesia
• Long term, 15 years positive effects
• Stem-cell-based regenerative therapy could transform PD therapy
• 1995  Fetal DA neuron grafting for PD in Switzerland
• 1998 – midbrain stem cell derived DA neuron
• 200-2003 – Stem cell in brain implantation in WashDC
• 2011 – Behavioral assays that are restored in mice
• Optogenetics: manipulating – Light on the brain – control animal’s neurons
• MOA of Graft function
• Dopamine neurons – Stratium area of the human brain
• From bench to bedside – WNT boost enhances EN1 expression
• Neuron melanin induction
• Manufacturing and QA testing: GMP – Off the shelf Allogenic Product
• 1,000 human dose equivalents
• cryopreserve
• MSK-DA01 is highly enriched for mDA neuron precursors without detectable hESC Contaminants
• FDA feedback and final steps to IND – PRE-IND MEETING: 2014, 2016
• GLP STUDIES:
• TUMORIGENICITY, BIODISTRIBUTION AND TOXISITY
• HISTOLOGY OF FINAL PRODUCT
• CLINICAL TRIAL DESIGN – STEM-PD – MSK and Weill Cornell Medicine
• HLA expression is absent in edited iPSC with expression of HLA-E to block NK clearance
• FUTURE: CRISPR
• ATLaS-PD – assessing the longitudinal Symptoms/signs to moderate of severe stage
• Development of a new PD therapy from Pluripotent Stem Cells
• BlueRock Therapeutics – MSK-PD – Start up – $240Million funding
• Stem cell based dopamine therapy for PD
• Immunosuppression for 12 months
• defined levodopa response > 45% improvement
• Conclusions
• Cell banks for clinical trials
• NY state Stem cell science consortia

http://www.brandeis.edu/rosenstiel/images/pdfs/gabbay21program.pdf