From the NIH Directors Blog by Dr. Francis Collins
Its a race against time when someone suffers a stroke caused by a blockage of a blood vessel supplying the brain. Unless clot-busting treatment is given within a few hours after symptoms appear, vast numbers of the brains neurons die, often leading to paralysis or other disabilities. It would be great to have a way to replace those lost neurons. Thanks to gene therapy, some encouraging strides are now being made.
In a recent study in Molecular Therapy, researchers reported that, in their mouse and rat models of ischemic stroke, gene therapy could actually convert the brains support cells into new, fully functional neurons.1 Even better, after gaining the new neurons, the animals had improved motor and memory skills.
For the team led by Gong Chen, Penn State, University Park, the quest to replace lost neurons in the brain began about a decade ago. While searching for the right approach, Chen noticed other groups had learned to reprogram fibroblasts into stem cells and make replacement neural cells.
As innovative as this work was at the time, it was performed mostly in lab Petri dishes. Chen and his colleagues thought, why not reprogram cells already in the brain?
They turned their attention to the brains billions of supportive glial cells. Unlike neurons, glial cells divide and replicate. They also are known to survive and activate following a brain injury, remaining at the wound and ultimately forming a scar. This same process had also been observed in the brain following many types of injury, including stroke and neurodegenerative conditions such as Alzheimers disease.
To Chens NIH-supported team, it looked like glial cells might be a perfect target for gene therapies to replace lost neurons. As reported about five years ago, the researchers were on the right track.2
The Chen team showed it was possible to reprogram glial cells in the brain into functional neurons. They succeeded using a genetically engineered retrovirus that delivered a single protein called NeuroD1. Its a neural transcription factor that switches genes on and off in neural cells and helps to determine their cell fate. The newly generated neurons were also capable of integrating into brain circuits to repair damaged tissue.
There was one major hitch: the NeuroD1 retroviral vector only reprogrammed actively dividing glial cells. That suggested their strategy likely couldnt generate the large numbers of new cells needed to repair damaged brain tissue following a stroke.
Fast-forward a couple of years, and improved adeno-associated viral vectors (AAV) have emerged as a major alternative to retroviruses for gene therapy applications. This was exactly the breakthrough that the Chen team needed. The AAVs can reprogram glial cells whether they are dividing or not.
In the new study, Chens team, led by post-doc Yu-Chen Chen, put this new gene therapy system to work, and the results are quite remarkable. In a mouse model of ischemic stroke, the researchers showed the treatment could regenerate about a third of the total lost neurons by preferentially targeting reactive, scar-forming glial cells. The conversion of those reactive glial cells into neurons also protected another third of the neurons from injury.
Studies in brain slices showed that the replacement neurons were fully functional and appeared to have made the needed neural connections in the brain. Importantly, their studies also showed that the NeuroD1 gene therapy led to marked improvements in the functional recovery of the mice after a stroke.
In fact, several tests of their ability to make fine movements with their forelimbs showed about a 60% improvement within 20 to 60 days of receiving the NeuroD1 therapy. Together with study collaborator and NIH grantee Gregory Quirk, University of Puerto Rico, San Juan, they went on to show similar improvements in the ability of rats to recover from stroke-related deficits in memory.
While further study is needed, the findings in rodents offer encouraging evidence that treatments to repair the brain after a stroke or other injury may be on the horizon. In the meantime, the best strategy for limiting the number of neurons lost due to stroke is to recognize the signs and get to a well-equipped hospital or call 911 right away if you or a loved one experience them. Those signs include: sudden numbness or weakness of one side of the body; confusion; difficulty speaking, seeing, or walking; and a sudden, severe headache with unknown causes. Getting treatment for this kind of brain attack within fourhours of the onset of symptoms can make all the difference in recovery.
This research was supported in part by NIA grant AG045656.
 Chen Y-C, et al. A NeuroD1 AAV-based gene therapy for functional brain repair after ischemic injury through in vivo astrocyte-to-neuron conversion. Molecular Therapy. 2019. Epub Sept. 6.
 Guo Z, et al. In vivo direct reprogramming of reactive glial cells into functional neurons after brain injury and in an Alzheimers disease model. Cell Stem Cell. 2014;14(2):188-202. doi: 10.1016/j.stem.2013.12.001.
See the original post here:
Gene therapy shows promise repairing brain tissue damaged by stroke - National Institute on Aging
- Stem Cell Transplants Used to Grow Fully Functional Lungs in Mice - Technology Networks - November 11th, 2019
- Human Heart Cells Transform in Space; Return to Normal on Earth: Study - The Weather Channel - November 11th, 2019
- Serving those who serve us - The Hub at Johns Hopkins - November 11th, 2019
- Kadimastem to Present Interim Results of Cohort A of Its Phase 1/2a Clinical Trial in ALS at the 7th International Stem Cell Meeting, in Tel-Aviv,... - November 11th, 2019
- The Value and Versatility of Clinical Flow Cytometry - Technology Networks - November 11th, 2019
- Global Cell Harvesting Industry Research: Key Companies Profile with Sales, Revenue, Market Share, Price and Competitive Situation Analysis - Inquiry... - November 11th, 2019
- Human heart cells are altered by spaceflight, but return mostly to normal on Earth - Space Daily - November 9th, 2019
- Jennifer OConnell: President Kanye in 2024? Be very afraid America - The Irish Times - November 9th, 2019
- Cord Blood Stem Cells Market Executive Summary, Introduction, Sizing, Analysis and Forecast To 2025 - Markets Gazette 24 - November 9th, 2019
- Global Animal Stem Cell Therapy Market - Industry Outlook and Forecast 2019-2024 - Real Viewpoint - November 9th, 2019
- Novel Molecule Reduces the Aggressiveness of Pediatric Cancer - Technology Networks - November 7th, 2019
- 2019s Allen Distinguished Investigators will focus on the mysteries of our cells - Yahoo Tech - November 7th, 2019
- At the American Academy of Stem Cell Physicians Live Congress 2019, FDA Safety Panel Says No to the Bad Actors - PRNewswire - November 7th, 2019
- MD Anderson Partners with Takeda to Develop CAR Natural Killer-Cell Therapy - Cancer Network - November 7th, 2019
- First UK patient treated with tissue engineered product for rare eye disease - Hospital Healthcare Europe - November 7th, 2019
- Spaceflight alters heart cells but they quickly recover back on Earth - New Scientist News - November 7th, 2019
- Stem Cell Assay Market To Witness Increase In Revenues By 2024 - Montana Ledger - November 7th, 2019
- Researchers Find Link Between Eye Disease And Degeneration Of The Brain - BioSpace - November 7th, 2019
- Physicians' Education Resource to Host Satellite Symposia at Annual American Society of Hematology Meeting and Exposition in Orlando - Business Wire - November 7th, 2019
- Keep Bioethics out of Elementary and High Schools - National Review - November 7th, 2019
- Stem Cell Cartilage Regeneration Market 2019, Trend, CAGR Status, Growth, Analysis and Forecast to 2025 - Virtualnewsusa - November 7th, 2019
- The Bold and the Beautiful Star Don Diamont Supports ALS Research - Soap Hub - November 7th, 2019
- International Conference on Stem Cells and Regenerative Medicine - Hoover Sun - November 5th, 2019
- Global Cancer Stem Cell Market Forecast to 2024 by Types, Application and by Regions - Exchange 99 - November 5th, 2019
- Lymphatic System Discovered To Play Key Role in Hair Regeneration - Technology Networks - November 5th, 2019
- Stem cell transplants approved for people with MS in Scotland - MS Trust - November 5th, 2019
- Johns Hopkins professor to lecture on interplay of secular bioethics, religion as part of Honors Colloquium - URI Today - November 5th, 2019
- Russell Brand Defends Lewis Hamiltons Vegan Hypocrisy and It Will Make You Think - LIVEKINDLY - November 5th, 2019
- Latest Report on Stem Cell Banking Market to Drive Amazing Growth by 2025 | Cord Blood Registry (CBR) Systems - News Hours Today - November 5th, 2019
- Global Stem Cell Cartilage Regeneration Market 2019, Trend, CAGR Status, Growth, Analysis and Forecast to 2024 - BeetleVersion - November 5th, 2019
- The House of Lords is needed to protect democracy now more than ever - The Independent - November 3rd, 2019
- Late-Term Abortion and an Election in Virginia - Newsmax - October 31st, 2019
- AIVITA Biomedical Announces Publication Detailing Immune Mechanisms Leading to Complete Remission of Measurable Metastatic Melanoma in Patient Treated... - October 31st, 2019
- CHS teacher enjoys prepping students for life out on their own - Albuquerque Journal - October 31st, 2019
- bluebird bio Reports Third Quarter 2019 Financial Results and Highlights Operational Progress - Business Wire - October 31st, 2019
- Global Cell Culture Protein Surface Coating Market: What it got next? Find out with the latest research available at 'The Market Reports' - Market... - October 31st, 2019
- SCD, HIV Gene Therapy Efforts Get $200M from NIH, Gates Foundation - Sickle Cell Anemia News - October 31st, 2019
- Global 3D Cell Culture Markets, 2019-2025: Cancer & Stem Cell Research Displays the Potential to Grow at Over 21.9% - ResearchAndMarkets.com -... - October 26th, 2019
- UCI IN THE NEWS OCT. 25, 2019 - UCI News - October 26th, 2019
- Mini-brains may already be sentient and suffering, scientists warn - Big Think - October 26th, 2019
- UK and China scientists developing new drugs to fight Tuberculosis - University of Birmingham - October 26th, 2019
- Global Stem Cell Therapy Market Global and Regional Analysis by Top Key Market Players, Key Regions, Product Segments, and Applications 2024 - Globe... - October 24th, 2019
- Do transhumanists need their own bill of rights? - Quartz - October 22nd, 2019
- Global Wound Care Market Outlook to 2024: New Product Approvals/Launches, Emergence of Stem Cell Therapy For Wound Healing - P&T Community - October 22nd, 2019
- New study reveals why breast cancer spreads to the brain - USC News - October 22nd, 2019
- Meet the axolotl: A cannibalistic salamander that regenerates its limbs and might help us better understand human stem cell therapy -... - October 22nd, 2019
- More awareness needed on stem cell donation: expert - The Hindu - October 22nd, 2019
- Lucknow: In a first, 26-yr-old DMD patient in UP survives with stem cell therapy - ETHealthworld.com - October 22nd, 2019
- Registration Open for The Eye and The Chip Research Congress - Newswise - October 22nd, 2019
- Cesca Therapeutics Forms Joint Venture with Healthbanks Biotech (USA) to Provide Immune Cell Banking and Cell Processing Services - P&T Community - October 22nd, 2019
- 'I've potentially saved a stranger's life by donating my blood stem cells and it was painless' - inews - October 22nd, 2019
- CST and Cell Press launch Cell Mentor in China - BSA bureau - October 22nd, 2019
- How stem cells are helping to mend broken hearts - Belfast Telegraph - October 22nd, 2019
- Iran sends US list of names for its proposed prisoner swap - Stars and Stripes - October 22nd, 2019
- Multiple Myeloma Experts, Patients, Advocates and Caregivers Team Up to Hike Through Patagonia - BioSpace - October 22nd, 2019
- Analysis Determines Cost Effectiveness of Various Treatment Strategies for Multiple Myeloma - Cancer Therapy Advisor - October 11th, 2019
- Stem cell therapy helped Owen Franks but there's still plenty to prove - Stuff.co.nz - October 11th, 2019
- AgeX Therapeutics to Present at Metabesity 2019 - Business Wire - October 11th, 2019
- Stem Cell Characterization Kits Market 08-Year Market Forecast and Trends Analysis Research Report - The Tribune City - October 10th, 2019
- New Cambridge research could lead to novel cancer therapies - Business Weekly - October 10th, 2019
- Global 3D Bioprinting Market Outlook, 2019-2024 - Market Anticipated to Reach $1.64 Billion by 2024 - ResearchAndMarkets.com - Business Wire - October 10th, 2019
- Stem Cell Cartilage Regeneration Market 2019: Prosperous Growth, Recent Trends and Demand by Top Key Vendors like Anika Therapeutics, Biomet,... - October 10th, 2019
- Industry Champion Jim Greenwood to Retire Following 2020 Elections - BioSpace - October 10th, 2019
- Cell Culture Protein Surface Coatings Market will Going to be Worth US$ 623.4 Mn by 2020 - Online News Guru - October 10th, 2019
- NIH funding bolsters rare diseases research collaborations | National Institutes of Health - National Institutes of Health - October 4th, 2019
- Stem Cell Therapy Market worth USD 4759.27 Million By 2024 - Global Market News 24 - October 4th, 2019
- Genome editing to be tested in kidney organoids - UW Medicine Newsroom - October 2nd, 2019
- First Patient Enrolled in Novel Stem Cell Trial for Heart Failure Treatment - Newswise - October 2nd, 2019
- Vor Biopharma Hires Senior Cell and Gene Therapy Leaders as Chief Technology Officer and Vice President of Research - Business Wire - October 2nd, 2019
- Now in development: off-the-shelf stem cells - Knowable Magazine - September 28th, 2019
- Immunity Against Cancer? Engineered Killer T Cells May Be the Key. - SciTechDaily - September 28th, 2019
- 'Provocative' Results With Stem Cells in Progressive MS - Medscape - September 27th, 2019
- 'I've Been Duped': Disabled Veteran Says He Spent Thousands at Health Center With No Improvement - NBC Bay Area - September 27th, 2019
- Finding alternatives to animal testing - University of California - September 27th, 2019
- Vitro Biopharma 3rd Quarter ended July 31st 2019 Financial Results of Operations - Yahoo Finance - September 27th, 2019
- Science Talk - Celebrating Professor Sir Mel Greaves and his legacy in leukaemia research - The Institute of Cancer Research - September 27th, 2019
- New restrictions put fetal tissue research in the balance - AAMCNews - September 25th, 2019
- 'I've Been Duped': Disabled Veteran Says He Spent Thousands at Health Center With No Improvement - NBC Southern California - September 25th, 2019
- New Research Suggests a Cure for HIV Could be on the Horizon - BioSpace - September 25th, 2019
- iSpecimen Increases Global Access to Hematopoietic Stem and Immune Cells - Business Wire - September 25th, 2019