Weill Cornell Medicine scientists have developed an innovative human neuron model that robustly simulates the spread of tau protein aggregates in the braina process that drives cognitive decline in Alzheimer's disease and frontotemporal dementia. This new model has led to the identification of novel therapeutic targets that could potentially block tau spread.
The preclinical study, published April 5 in Cell, is a significant advancement in Alzheimer's disease research.
Dr. Li Gan. Credit: John Abbott
Currently no therapies can stop the spread of tau aggregates in the brains of patients with Alzheimers disease," said lead study author, Dr. Li Gan, director of the Helen and Robert Appel Alzheimers Disease Research Institute and the Burton P. and Judith B. Resnick Distinguished Professor in Neurodegenerative Diseases in theFeil Family Brain and Mind Research Instituteat Weill Cornell Medicine. Our human neuron model of tau spread overcomes the limitations of previous models and has unveiled potential targets for drug development that were previously unknown.
Human pluripotent stem cells can develop into any cell of the body and can be coaxed to become neurons to model brain diseases in a lab dish. However, it had been nearly impossible to model tau propagation in these young neurons, as tau propagation requires decades in aging brains.
Celeste Parra Bravo
Dr. Gans team used CRISPR technology to modify the genomes of human stem cells, prompting them to express forms of tau associated with diseased aging brains. "This model has been a game-changer, simulating tau spread in neurons within weeksa process that would typically take decades in the human brain," Dr. Gan said.
In their quest to halt tau propagation, Dr. Gan's team employed CRISPRi screening to disable 1,000 genes to ascertain their roles in tau spread. They discovered 500 genes that have a significant impact on tau abundance.
Dr. Shiaoching Gong
CRISPRi technology allowed us to use unbiased approaches to look for drug targets, not confined to what was previously reported by other scientists, said one of the lead study authors Celeste Parra Bravo, a neuroscience doctoral candidate in the Weill Cornell Graduate School of Medical Sciences working in the Gan lab.
One discovery includes the UFMylation cascade, a cellular process involving the attachment of a small protein named UFM1 to other proteins. This process's connection to tau spread was previously unknown. Post-mortem studies of brains from patients with Alzheimers disease found that UFMylation is altered, and the team also found in preclinical models that inhibition of the enzyme required for UFMylation blocks tau propagation in neurons.
We are particularly encouraged by the confirmation that inhibiting UFMylation blocked tau spread in both human neurons and mouse models, said paper co-author Dr. Shiaoching Gong, associate professor of research in neuroscience in the Appel Instituteat Weill Cornell Medicine.
Many Alzheimers disease treatments initially show promise in mouse models but do not succeed in clinical trials, Dr. Gan said. With the new human cell model, she is optimistic about the path ahead. "Our discoveries in human neurons open the door to developing new treatments that could truly make a difference for those suffering from this devastating disease."
Many Weill Cornell Medicine physicians and scientists maintain relationships and collaborate with external organizations to foster scientific innovation and provide expert guidance. The institution makes these disclosurespublic to ensure transparency. For this information, see profile forDr. Li Gan.
This research was supported in part by the National Institute of Neurological Disorders and Stroke, the National Institute on Aging and the National Institute of General Medical Sciences, all part of the National Institutes of Health, through grant numbers U54NS100717, R01AG072758, R01AG054214, R01AG074541, R25GM130494, and R01AG064239. Additional support was provided by the Rainwater Charitable Foundation and the JPB Foundation.
Excerpt from:
Human Neuron Model Paves the Way for New Alzheimer's Therapies - Weill Cornell Medicine Newsroom
- Congress Gives Stem Cells Another Shot -ASK THE EXPERT- ... [Last Updated On: August 4th, 2011] [Originally Added On: August 4th, 2011]
- Stem Cell Game 3- Grow with the Flow [Last Updated On: August 5th, 2011] [Originally Added On: August 5th, 2011]
- PROSTATE CANCER and stem cells [Last Updated On: August 13th, 2011] [Originally Added On: August 13th, 2011]
- Preview: 21st Century Snake Oil [Last Updated On: September 2nd, 2011] [Originally Added On: September 2nd, 2011]
- Stem cells: the future of medicine? [Last Updated On: September 5th, 2011] [Originally Added On: September 5th, 2011]
- Stem Cells: Politics vs. Medicine [Last Updated On: September 5th, 2011] [Originally Added On: September 5th, 2011]
- Mesenchymal Stem Cells in Regenerative Medicine: Of Hopes and Challenges [Last Updated On: September 5th, 2011] [Originally Added On: September 5th, 2011]
- An amazing story of stem cells, regenerative medicine and healing power: [Last Updated On: September 6th, 2011] [Originally Added On: September 6th, 2011]
- Preserving Stem Cells: Regenerative Medicine [Last Updated On: September 9th, 2011] [Originally Added On: September 9th, 2011]
- TEDxPhoenix - Jane Maienschein - Stem Cells, Regenerative Medicine and Us [Last Updated On: September 11th, 2011] [Originally Added On: September 11th, 2011]
- Personalized Medicine: Stem Cells 1/2 [Last Updated On: September 14th, 2011] [Originally Added On: September 14th, 2011]
- A Century of Stem Cells - Johns Hopkins Medicine [Last Updated On: September 16th, 2011] [Originally Added On: September 16th, 2011]
- What are stem cells? How can they be used for medical benefit? [Last Updated On: September 17th, 2011] [Originally Added On: September 17th, 2011]
- STEM CELLS TRANSLATIONAL MEDICINE Official Announcement [Last Updated On: September 18th, 2011] [Originally Added On: September 18th, 2011]
- Turning Adult Stem Cells into Medicine - Zannos Grekos, MD [Last Updated On: September 18th, 2011] [Originally Added On: September 18th, 2011]
- A New Era in Regenerative Medicine [Last Updated On: September 24th, 2011] [Originally Added On: September 24th, 2011]
- Bruce Conklin: Drug screening with stem cells [Last Updated On: September 27th, 2011] [Originally Added On: September 27th, 2011]
- Professors Chandran and ffrench-constant - Are stem cells the future of regenerative medicine? [Last Updated On: September 27th, 2011] [Originally Added On: September 27th, 2011]
- Hormone Myths vs. Medical Literature and How to Grow Your Own Stem Cells - Ronald Rothenberg, MD [Last Updated On: September 28th, 2011] [Originally Added On: September 28th, 2011]
- Cardiovascular Derivatives of Embryonic Stem Cells in Cardiac Repair and Drug Discovery [Last Updated On: September 29th, 2011] [Originally Added On: September 29th, 2011]
- Jackson Laboratory symposium: What's vital for effective stem cell therapies? [Last Updated On: September 30th, 2011] [Originally Added On: September 30th, 2011]
- Alzheimer's Disease: Spotlight on Stem Cell Research - Rod Shankle [Last Updated On: October 3rd, 2011] [Originally Added On: October 3rd, 2011]
- "StemEnhance" the Biggest Scientific [Last Updated On: October 4th, 2011] [Originally Added On: October 4th, 2011]
- Stem cell medical breakthrough? [Last Updated On: October 4th, 2011] [Originally Added On: October 4th, 2011]
- The Future of Stem Cells and Regenerative Medicine [Last Updated On: October 4th, 2011] [Originally Added On: October 4th, 2011]
- Stem Cell Clinical Trials : University of Miami Miller School of Medicine [Last Updated On: October 4th, 2011] [Originally Added On: October 4th, 2011]
- Medical tourism in Croatia - Regenerative medicine-Stem cells in reconstructive surgery [Last Updated On: October 4th, 2011] [Originally Added On: October 4th, 2011]
- Bioethics Stem Cells and the New Biology [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- Stem Cells: The Hope The Hype and the Science [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- Skin Stem Cells: Their Biology [Last Updated On: October 6th, 2011] [Originally Added On: October 6th, 2011]
- Spotlight on Cancer Stem Cell Research [Last Updated On: October 6th, 2011] [Originally Added On: October 6th, 2011]
- Lou Gehrig's Disease (ALS): UCSD Team's Stem Cell Therapy Rationale [Last Updated On: October 6th, 2011] [Originally Added On: October 6th, 2011]
- Sickle Cell Anemia: Stem Cell Gene Therapy - Donald Kohn [Last Updated On: October 6th, 2011] [Originally Added On: October 6th, 2011]
- Stem Cells and Parkinson's Disease [Last Updated On: October 6th, 2011] [Originally Added On: October 6th, 2011]
- Stem Cell Research: Macular Degeneration [Last Updated On: October 6th, 2011] [Originally Added On: October 6th, 2011]
- An amazing story of stem cells and regenerative medicine [Last Updated On: October 6th, 2011] [Originally Added On: October 6th, 2011]
- Stem Cell City - Lisa Ray [Last Updated On: October 6th, 2011] [Originally Added On: October 6th, 2011]
- Stem Cell Therapy: Healing Force of the future [Last Updated On: October 6th, 2011] [Originally Added On: October 6th, 2011]
- Adult Stem Cells in Drug Discovery and Therapeutics [Last Updated On: October 7th, 2011] [Originally Added On: October 7th, 2011]
- Medical Breakthrough: First Stem Cell Procedure [Last Updated On: October 7th, 2011] [Originally Added On: October 7th, 2011]
- Dr. Judith Oppenheim, Chicago on Dental Stem Cells on WGN-TV's Medical Watch. [Last Updated On: October 9th, 2011] [Originally Added On: October 9th, 2011]
- Jerome Zack: Creating iPS Cells - Video [Last Updated On: October 14th, 2011] [Originally Added On: October 14th, 2011]
- Sight for sore eyes - Video [Last Updated On: October 15th, 2011] [Originally Added On: October 15th, 2011]
- Regenerative Medicine Update: Stem Cells and Functional Testing - Mitchell J. Ghen, DO, PhD - Video [Last Updated On: October 15th, 2011] [Originally Added On: October 15th, 2011]
- Stem cells as the future of medicine - Video [Last Updated On: October 18th, 2011] [Originally Added On: October 18th, 2011]
- Neural Stem Cells Reverse Alzheimer's-Like Symptoms - Video [Last Updated On: October 19th, 2011] [Originally Added On: October 19th, 2011]
- Deafness: Spotlight on Stem Cell Research - Ebenezer Yamoah - Video [Last Updated On: October 21st, 2011] [Originally Added On: October 21st, 2011]
- Leukemia: Spotlight on Stem Cell Research - Patient Stories - Video [Last Updated On: October 21st, 2011] [Originally Added On: October 21st, 2011]
- Epidermolysis Bullosa: Corrected iPS Stem Cell-Based Therapy - Video [Last Updated On: October 21st, 2011] [Originally Added On: October 21st, 2011]
- iPS Stem Cell-Based Treatment of Epidermolysis Bullosa - Video [Last Updated On: October 21st, 2011] [Originally Added On: October 21st, 2011]
- Parkinson's Disease: Spotlight on Stem Cell Research - Arnold Kriegstein - Video [Last Updated On: October 21st, 2011] [Originally Added On: October 21st, 2011]
- Closing Remarks, Screening Stem Cells 2009: From Reprogramming to Regenerative Medicine - Video [Last Updated On: October 23rd, 2011] [Originally Added On: October 23rd, 2011]
- The Sue and Bill Gross Stem Cell Regenerative Medicine Center at UCI - Video [Last Updated On: October 26th, 2011] [Originally Added On: October 26th, 2011]
- Stem Cell Institute - Video [Last Updated On: October 28th, 2011] [Originally Added On: October 28th, 2011]
- StemCellTV Special Report - Stem Cell Therapy a "Medical Game Changer" - Video [Last Updated On: October 28th, 2011] [Originally Added On: October 28th, 2011]
- Adult Stem Cells and Regeneration - Video [Last Updated On: November 8th, 2011] [Originally Added On: November 8th, 2011]
- Cloned Embryonic Stem Cells, FIRST (Brainstorm Ep26) - Video [Last Updated On: November 12th, 2011] [Originally Added On: November 12th, 2011]
- Beating Heart Stem Cells - Video [Last Updated On: November 13th, 2011] [Originally Added On: November 13th, 2011]
- Stem Cell Research In Toronto - Video [Last Updated On: November 13th, 2011] [Originally Added On: November 13th, 2011]
- Stem Cells and Their Amazing Potential 2011 trailer - Video [Last Updated On: November 15th, 2011] [Originally Added On: November 15th, 2011]
- Stemcell Research and Aging - Panel 1 - Video [Last Updated On: December 13th, 2011] [Originally Added On: December 13th, 2011]
- Austin Forum - Nov 1st (Part 4 of 4) - Video [Last Updated On: December 13th, 2011] [Originally Added On: December 13th, 2011]
- Vet-Stem Medistem Cellmedicine Rheumatoid Arthritis Stem Cell Video - Video [Last Updated On: December 19th, 2011] [Originally Added On: December 19th, 2011]
- Stem Cell Clinical Trial for Heart Failure: Eduardo Marban - CIRM Spotlight on Disease - Video [Last Updated On: December 26th, 2011] [Originally Added On: December 26th, 2011]
- Stem Cell-Derived Heart Cells: Bruce Conklin - CIRM Science Writer's Seminar - Video [Last Updated On: January 5th, 2012] [Originally Added On: January 5th, 2012]
- Pope gives support to adult stem cells and asks for ethics in scientific research - Video [Last Updated On: January 5th, 2012] [Originally Added On: January 5th, 2012]
- Stem Cell Treatment for Rheumatoid Arthritis - Darnell Morris - Video [Last Updated On: January 5th, 2012] [Originally Added On: January 5th, 2012]
- Personalized Medicine: Stem Cells 2/2 - Video [Last Updated On: January 13th, 2012] [Originally Added On: January 13th, 2012]
- Utilizing Stem Cell-derived Cardiomyocytes for Early Safety Screening - Webinar Presentation - Video [Last Updated On: January 22nd, 2012] [Originally Added On: January 22nd, 2012]
- Stem Cell Stage Bypassed in Skin Cell to Brain Cell Transformation [Last Updated On: February 1st, 2012] [Originally Added On: February 1st, 2012]
- Encouraging Results with Stem Cell Transplant for Brain Injury [Last Updated On: February 1st, 2012] [Originally Added On: February 1st, 2012]
- Stem cell injection successfully treats urinary incontinence [Last Updated On: February 13th, 2012] [Originally Added On: February 13th, 2012]
- ImmunoCellular Therapeutics To Present at Targeting Stem Cells Symposium during 19th Annual Molecular Medicine Tri ... [Last Updated On: February 17th, 2012] [Originally Added On: February 17th, 2012]
- Adult Stem Cell Success Stories - Barry Goudy - Video [Last Updated On: February 21st, 2012] [Originally Added On: February 21st, 2012]
- Stem Cell Treatment for T-6 Spinal Cord Injury - Video [Last Updated On: February 21st, 2012] [Originally Added On: February 21st, 2012]
- Stem Cells China-Switzerland.wmv - Video [Last Updated On: February 21st, 2012] [Originally Added On: February 21st, 2012]
- Stem cell find offers hope for infertility [Last Updated On: February 27th, 2012] [Originally Added On: February 27th, 2012]
- Stem cell fertility treatments could be risky for older women [Last Updated On: February 28th, 2012] [Originally Added On: February 28th, 2012]
- A*STAR Scientists Make Groundbreaking Discovery on Stem Cell Regulation [Last Updated On: March 1st, 2012] [Originally Added On: March 1st, 2012]
- UGA study reveals basic molecular 'wiring' of stem cells [Last Updated On: March 1st, 2012] [Originally Added On: March 1st, 2012]