Breakthrough to halt premature aging of cells – ScienceBlog.com
By daniellenierenberg
Capping decades of research, a new study may offer a breakthrough in treatingdyskeratosis congenitaand other so-called telomere diseases, in which cells age prematurely.
Using cells donated by patients with the disease, researchers at theDana-Farber/Boston Childrens Cancer and Blood Disorders Centeridentified several small molecules that appear to reverse this cellular aging process.Suneet Agarwal, the studys senior investigator, hopes at least one of these compounds will advance toward clinical trials. Findings werepublished Tuesday in the journal Cell Stem Cell.
If so, it could be the first treatment for dyskeratosis congenita, or DC, that could reverse all of the diseases varying effects on the body. The current treatment, bone marrow transplant, is high-risk, and only helps restore the blood system, whereas DC affects multiple organs.
The compounds identified in the study restore telomeres, protective caps on the tips of our chromosomes that regulate how our cells age. Telomeres consist of repeating sequences of DNA that get shorter each time a cell divides.
The bodys stem cells, which retain their youthful qualities, normally make an enzyme called telomerase that builds telomeres back up again. But when telomeres cant be maintained, tissues age before their time. A spectrum of diseases can result not just DC, but also aplastic anemia, liver cirrhosis, and pulmonary fibrosis.
The discovery of telomerase 35 years ago, earninga Nobel Prize in 2009, galvanized the scientific world. Subsequent studies suggested the enzyme could be a key to reversing aging, as well as treating cancer, in which malignant cells become immortal and divide indefinitely.
For years, researchers have tried to find a simple and safe way to manipulate telomerase, preserve telomeres, and create cures for telomere diseases.
Once human telomerase was identified, there were lots of biotech startups, lots of investment, says Agarwal, who has researched the biology of telomerase for the past decade. But it didnt pan out. There are no drugs on the market, and companies have come and gone.
DC can be caused by mutations in any of multiple genes. Most of these mutations disrupt telomerase formation or function in particular, by disrupting two molecules called TERT and TERC that join together to form telomerase. TERT is an enzyme made in stem cells, and TERC is a so-called non-coding RNA that acts as a template to create telomeres repeating DNA sequences. Both TERT and TERC are affected by a web of other genes that tune telomerases action.
One of these genes is PARN. In 2015, Agarwal and colleagues showed inNatureGeneticsthat PARN is important for processing and stabilizing TERC. Mutations in PARN mean less TERC, less telomerase, and prematurely shortened telomeres.
Thenew study, led by Harvard Medical School postdoctoral fellow Neha Nagpal, delved further, focusing on an enzyme that opposes PARN and destabilizes TERC, called PAPD5.
We thought if we targeted PAPD5, we could protect TERC and restore the proper balance of telomerase, says Nagpal, first author on the paper.
Nagpal and her colleagues first conducted large-scale screening studies to identify PAPD5 inhibitors, testing more than 100,000 known chemicals. They got 480 initial hits, which they ultimately narrowed to a small handful.
They then tested the inhibitors in stem cells made from the Martins cells and those of other patients with DC. To the teams delight, the compounds boosted TERC levels in the cells and restored telomeres to their normal length.
But the real challenge was to see if the treatment would be safe and specific, affecting only the stem cells bearing TERT. To test this, the team introduced DC-causing PARN mutations into human blood stem cells, transplanted those cells into mice, then treated the mice with oral PAPD5 inhibitors. The compounds boosted TERC and restored telomere length in the transplanted stem cells, with no adverse effect on the mice or on the ability to form different kinds of blood cells.
This provided the hope that this could become a clinical treatment, says Nagpal.
In the future, Agarwal, Nagpal, and colleagues hope to validate PAPD5 inhibition for other diseases involving faulty maintenance of telomeres and perhaps even aging itself. They are most excited about two compounds, known as BCH001 and RG7834 that are under further development.
We envision these to be a new class of oral medicines that target stem cells throughout the body, Agarwal says. We expect restoring telomeres in stem cells will increase tissue regenerative capacity in the blood, lungs, and other organs affected in DC and other diseases.
One email, each morning, with our latest posts. From medical research to space news. Environment to energy. Technology to physics.
Thank you for subscribing.
Something went wrong.
See the original post:
Breakthrough to halt premature aging of cells - ScienceBlog.com
- 1st stem cell therapy, new HIV drug approved - ecns - January 5th, 2025
- Suppression of thrombospondin-1mediated inflammaging prolongs hematopoietic health span - Science - January 5th, 2025
- A pilot raced through the airport to surprise an old friend: the woman who saved his life - CNN - December 27th, 2024
- Types of Stem Cell and Bone Marrow Transplants - December 27th, 2024
- Explained: What is mesenchymal stem cell therapy? - Drug Discovery News - December 18th, 2024
- Stem Cell Transplants Offer New Hope for Saving the Worlds Corals - Technology Networks - December 18th, 2024
- Scientists Present Research on Novel Cancer Therapies at ASH - City of Hope - December 18th, 2024
- Navigating CAR-T cell therapy long-term complications - Nature.com - December 18th, 2024
- High-dose chemotherapy followed by autologous stem cell transplant ineffective for patients with mantle cell lymphoma - News-Medical.Net - December 18th, 2024
- Stem Cell Therapy Market Is Expected To Reach Revenue Of - GlobeNewswire - December 18th, 2024
- The Importance of Cellular Therapy in the Clinical Case of a Young Man With a Challenging Precursor B-cell Lymphoblastic Leukemia - Cureus - December 18th, 2024
- A search for the perfect match, Apex six year old in need of donor - CBS17.com - December 18th, 2024
- New insights into survival of breast cancer cells in the bone marrow - News-Medical.Net - December 9th, 2024
- Cellular trafficking and fate mapping of cells within the nervous system after in utero hematopoietic cell transplantation - Nature.com - December 9th, 2024
- Saving lives, one stem cell at a time - Texas A&M The Battalion - December 9th, 2024
- Turn Biotechnologies Announces Landmark Study to Assess Effectiveness of ERA Therapy in Restoring Bone Marrow - PR Newswire UK - December 9th, 2024
- Orca Bio Presents Three-Year Survival Data with Orca-T in Patients with Hematological Malignancies at the 66th ASH Annual Meeting - Yahoo Finance - December 9th, 2024
- You are the match. How UNC student honored her late grandfather with life-saving effort - Raleigh News & Observer - November 29th, 2024
- scRNA-seq revealed transcriptional signatures of human umbilical cord primitive stem cells and their germ lineage origin regulated by imprinted genes... - November 29th, 2024
- Atlanta pilot with an aggressive cancer finds lifesaving help from a stranger and a simple test - The Atlanta Journal Constitution - November 29th, 2024
- Researchers have brought the promise of stem cell therapies closer to reality - The Week - November 29th, 2024
- Bone Marrow Donors Can Be Hard to Find. One Company Is Turning to ... - November 15th, 2024
- Hematopoietic Stem Cells and Their Niche in Bone Marrow - November 15th, 2024
- Bone Marrow Transplant Program - Overview - Mayo Clinic - November 15th, 2024
- Bone Marrow Donors Can Be Hard to Find. One Company Is Turning to Cadavers - WIRED - November 15th, 2024
- More stem cells for sickle cell gene therapy readied with motixafortide - Sickle Cell Disease News - November 15th, 2024
- Skull bone marrow expands throughout life and remains healthy during aging, researchers discover - Medical Xpress - November 15th, 2024
- Adult skull bone marrow is an expanding and resilient haematopoietic reservoir - Nature.com - November 15th, 2024
- Evaluation of standard fludarabine dosing and corresponding exposures in infants and young children undergoing hematopoietic cell transplantation -... - November 15th, 2024
- Stem cells grown in space show super powers but theres a catch - Study Finds - November 15th, 2024
- Getting a Stem Cell or Bone Marrow Transplant - October 21st, 2024
- Acquisition of durable insulin-producing cells from human adipose tissue-derived mesenchymal stem cells as a foundation for cell- based therapy of... - October 21st, 2024
- 1.5 Lakh Indians Register To Save Lives: Join the Mission To Fight Blood Cancer - The Better India - October 21st, 2024
- How Stem Cell and Bone Marrow Transplants Are Used to Treat Cancer - October 13th, 2024
- Stem Cell (Bone Marrow) Transplants - MD Anderson Cancer Center - October 13th, 2024
- Donating Bone Marrow and Stem Cells: The Process and What To Expect - October 13th, 2024
- What to expect as a stem cell or bone marrow donor - October 13th, 2024
- Structural organization of the bone marrow and its role in ... - October 13th, 2024
- Stem cell donor from down the road saved my life after global search - BBC.com - September 23rd, 2024
- Awaiting the call: family hopes to find blood stem cell donor - Claremont Courier - September 23rd, 2024
- Michigan woman one of first in world to successfully receive bone marrow from deceased donor - WDIV ClickOnDetroit - September 23rd, 2024
- Next-generation stem cell transplant: Revolutionizing a lifesaving cancer therapy - The Business Journals - September 23rd, 2024
- Sophie's life was saved by a stranger. Some in her position have an 'unfair' disadvantage - SBS News - September 23rd, 2024
- What Are Leukemia and Lymphoma and How Are They Treated? - LVHN News - September 23rd, 2024
- Giralt on MDS Transplant Timing and Candidacy - Targeted Oncology - September 14th, 2024
- Aging is associated with functional and molecular changes in distinct hematopoietic stem cell subsets - Nature.com - September 14th, 2024
- A practical guide to therapeutic drug monitoring in busulfan: recommendations from the Pharmacist Committee of the European Society for Blood and... - September 14th, 2024
- ISU researcher blown away by blood cell replication discovery - Radio Iowa - September 14th, 2024
- Pausing biological clock could give boost to lab-produced blood stem cells - Phys.org - September 14th, 2024
- 9-year-old gets successful bone marrow transplant - The Times of India - September 14th, 2024
- Dr. Crandall: Stem Cell Treatment Heals the Heart - Newsmax - September 3rd, 2024
- Orion Corporation: Managers’ transactions – Hao Pan - August 19th, 2024
- BioCorRx Reports Business Update for the Second Quarter of 2024 - August 19th, 2024
- Tevogen Bio Reports Second Quarter 2024 Financial Results, Eliminates Doubt About Company’s Ability to Continue as a Going Concern, Eliminates... - August 19th, 2024
- Aligos Therapeutics Announces Reverse Stock Split - August 19th, 2024
- Lumos Pharma to Participate in H.C. Wainwright 26th Annual Global Investment Conference - August 19th, 2024
- Protect Pharmaceutical Corp. (PRTT) Announces New CEO and New Director; Moves to Finalize the Karinca Logistics Merger - August 19th, 2024
- OKYO Pharma Participates in H.C. Wainwright 4th Annual Ophthalmology Virtual Conference - August 19th, 2024
- CORRECTION – Tevogen Bio Reports Second Quarter 2024 Financial Results, Eliminates Doubt About Company’s Ability to Continue as a Going Concern,... - August 19th, 2024
- NurExone Biologic Achieves Key Milestone in Support of Robust Exosome Manufacturing Process - August 19th, 2024
- Silexion Therapeutics Ltd. and Moringa Acquisition Corp Announce Closing of their Business Combination - August 19th, 2024
- Vericel Announces FDA Approval of NexoBrid for the Treatment of Pediatric Patients with Severe Thermal Burns - August 19th, 2024
- Codexis Publishes FY2023 Sustainability Disclosures - August 19th, 2024
- MediWound Announces U.S. Food and Drug Administration Approval of NexoBrid® for the Treatment of Pediatric Patients with Severe Thermal Burns - August 19th, 2024
- First Successful Paediatric Allogeneic Bone Marrow Transplant In Bengaluru; Know All About The Procedure - Onlymyhealth - August 4th, 2024
- Is Stem Cell Transplant Often The Only Treatment Option For Blood Cancer Patients? Why So? - News18 - June 2nd, 2024
- This Swedish startup wants to reduce the cost, and controversy, around stem cell production - TechCrunch - March 10th, 2024
- Bone Marrow Transplantation | Johns Hopkins Medicine - December 20th, 2023
- Mansour bin Zayed witnesses inauguration of ADSCC Bone Marrow Transplant & Cellular Therapy Congress 2023 - ZAWYA - November 26th, 2023
- ADSCC Bone Marrow Transplant and Cellular Therapy Congress 2023 to take place in Abu Dhabi - ZAWYA - November 18th, 2023
- Orchard Therapeutics Reports First Quarter 2023 Financial Results and Announces Initiation of Rolling Submission for Biologics License Application of... - May 16th, 2023
- Family of 7-month-old in need of bone marrow transplant hosting donor registration event - CBS Pittsburgh - May 8th, 2023
- Anika Continues to Expand Addressable Market for Tactoset Injectable Bone Substitute with Additional 510(k) Clearance from FDA - Marketscreener.com - April 5th, 2023
- MorphoSys Completes Enrollment of Phase 3 MANIFEST-2 Study of Pelabresib in Myelofibrosis with Topline Results Expected by End of 2023 -... - April 5th, 2023
- VOR BIOPHARMA INC. Management's Discussion and Analysis of Financial Condition and Results of Operations (form 10-K) - Marketscreener.com - March 25th, 2023
- BioRestorative Therapies to Seek FDA Approval to Expand the Clinical Application of BRTX-100 - Marketscreener.com - March 17th, 2023
- BioSenic delivers a new post-hoc analysis of its Phase III JTA-004 trial on knee osteo-arthritis with positive action on the most severely affected... - March 17th, 2023
- JASPER THERAPEUTICS, INC. MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS (form 10-K) - Marketscreener.com - March 9th, 2023
- For a range of unmet medical needs, India offers a fantastic opportunity to push cell and gene therapies: B .. - ETHealthWorld - March 9th, 2023
- NGM BIOPHARMACEUTICALS INC Management's Discussion and Analysis of Financial Condition and Results of Operations. (form 10-K) - Marketscreener.com - March 1st, 2023