image:Jessica Bush, a graduate student at the Skaggs Graduate School for Chemical Biology at Scripps Research in Jupiter, Florida, goes over her experiments with Chemistry Professor Matthew Disney, PhD, and Research Associate Haruo Aikawa, PhD. The team published a study in Science Translational Medicine that describes a way of targeting inherited ALS and frontotemporal dementia. view more
Credit: Scott Wiseman for Scripps Research
JUPITER, FL One of the most commonly inherited forms of ALS and frontotemporal dementia is referred to as C9 ALS/FTD, so named for the repeated section of DNA on chromosome 9 that causes it. A collaboration led by scientists at Scripps Research in Florida has successfully treated the genetic disease in mice, with a potential drug molecule engineered in the lab of chemist Matthew Disney, PhD. The compound works in a new way, by directing the cells own immune machinery to degrade and eliminate the disease-causing RNA.
The teams study is published Wednesday in the journal Science Translational Medicine. Collaborators include Leonard Petrucelli, PhD, of the Mayo Clinic in Jacksonville, and Jeffrey Rothstein, MD, PhD, of Johns Hopkins University in Baltimore.
Also known as Lou Gehrigs disease, ALS causes progressive loss of motor neurons, the elongated nerve cells that connect muscles to the central nervous system. As motor neurons die, paralysis, muscle loss, swallowing and eventually, breathing difficulties develop, leading ultimately to death. Scientists are learning that ALS has multiple causes, some of them sporadic, and some inherited or familial.
Frontotemporal dementia similarly has both familial and sporadic causes. It involves progressive damage to neurons in the brains frontal and temporal lobes. Symptoms may include difficulty walking or odd behavioral and emotional states. Like ALS, there is no cure for frontotemporal dementia.
One disease, many symptoms
While people with FTD appear outwardly to have a completely different illness than people with ALS, those whose condition is caused by the C9 genetic repeat have the same disease. Manifestations differ according to cell types affected. The more times the sequence repeats, the earlier and more severe the disease symptoms.
The disease-causing mutations involve repeats of the nucleotides guanine and cytosine, specifically repeats of GGGGCC segments on chromosome 9, open reading frame 72. The number of disease-causing repeats can range from around 60 into the thousands. People who inherit the diseased gene can develop ALS, FTD or both. Studies have estimated that around 1 in 5 people diagnosed with familial ALS, and around 1 in 10 people with familial FTD carry the C9 mutations. The average age of symptom onset is 58.
This is a disease that runs in families. Based on the number of repeats, doctors can assess whether a patient would be affected with the disease. So, you know before a patient has symptoms that they have a high likelihood of developing it, and yet there is no treatment, Disney says. That makes it even more imperative to develop strategies to that could create a medicine.
A team effort
To assess the effectiveness of their compounds, the team needed both diagnostic biomarkers and patient-derived neurons displaying the C9 mutations. The Petrucelli group at Mayo Clinic has extensively studied C9 ALS/FTD and developed the diagnostic biomarkers. The Rothstein group at Johns Hopkins treats and researches ALS and provided stem cells, which the Disney Lab then brought forward into neurons that displayed the diseased array of GGGGCC repeats.
In their research, Disneys team designed a compound that targeted the RNA involved in transcribingthe gene causing the disease. The compound causes an interaction between the RNA and pathways that a cell uses to eliminate RNAs. The compound eliminated 70 percent of the toxic protein fragments from mice bread to have the disease, and removed most hallmarks of the disease from the patient-derived nerve cells.
A single injection in the mice showed benefit through the entire length of the study period, which was six weeks, says Jessica Bush, a graduate student at Scripps Research's Skaggs Institute for Chemical Biology, who was the papers first author.
I think that its so exciting that we can look at a disease like ALS, and by taking a different approach or new perspective, we can open the door to a whole new world of possibilities, and start down the road toward therapies, Bush says.
Basic science behind the discovery
Disney designed the compound by applying nearly 15 years of his groups research on finding druggable structures on RNA, a notoriously changeable and transient molecule, and building a library of compounds able to bind those druggable structures.
The successful compound works by binding tightly to the disease-causing RNA in multiple places, while also attracting an enzyme that eliminates RNAs. Nature apparently created the degrading enzyme to defend cells from viral infection and provide quality control for protein production.
We co-opt a natural process to eliminate disease-causing RNA, Disney says. A full analysis of the RNAs in the cells treated with the compound showed it was very specific and selective.
Moving the technology forward to where it can be tested in humans requires a large amount of additional tests and refinements, a process that may take several years, Disney adds.
These studies, we hope, will advance new ways of targeting the RNA that causes ALS as well as other diseases, he says. There is a possibility here to eventually treat these patients before they develop symptoms, but it will be a long road before reaching the clinic.
Science Translational Medicine
Experimental study
Animals
Ribonuclease recruitment using a small molecule reduced c9ALS/FTD r(G4C2) repeat expansion in vitro and in vivo ALS models
27-Oct-2021
M.D.D. is a founder of Expansion Therapeutics. M.D.D. is a consultant for Expansion Therapeutics, and E.T.W. was a consultant for Expansion Therapeutics during the course of these studies. A patent disclosure has been filed on aspects of this work.
Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.
Read the rest here:
ALS and dementia attacked by an RNA-hunting compound that recruits cell's own virus fighter - EurekAlert
- Organoids: science fiction or the future of pre-clinical studies? - Lexology - October 13th, 2022
- Researchers develop method to study brain connectivity, functionality - Florida Hospital News and Healthcare Report - South Florida Hospital News - October 13th, 2022
- A win for stem cells | Washington Examiner - October 4th, 2022
- TransMedia Group to Illumine Impressive Neuro Healing Results Achieved by Raymond Cralle, a Pioneer in Hyperbaric Oxygen Therapy and a Florida... - September 16th, 2022
- Sure Signs You Have Non-Hodgkin's Lymphoma Eat This Not That - Eat This, Not That - August 22nd, 2022
- New treatment changing outlook for those with blood cancers - WBAL TV Baltimore - July 19th, 2022
- Engineering Graduate Fellows Get Hands-on Experience with National Industry Leaders - UCF - July 11th, 2022
- New Alzheimer's Treatment on Horizon as Dementia Reversed for First Time in Dogs - StreetInsider.com - June 22nd, 2022
- Life Cycle of a Moss - Infographic - STEM Lounge - June 13th, 2022
- Miller School Researchers on the Trail to Unraveling Long COVID-19 - Florida Hospital News and Healthcare Report - South Florida Hospital News - June 4th, 2022
- American Academy of Stem Cell Physicians is Proud to Add to the Speaker Roster, Dr. Scheffer Tseng, Acclaimed Opthamologist and Founder of Bio-Tissue... - May 15th, 2022
- 'Doctors gave me six months to live in 2016 but I continue to defy every expectation' - Wales Online - May 2nd, 2022
- Revolutionary Oxygen Healing Therapy Now Available in Florida - Digital Journal - March 25th, 2022
- Global Mesenchymal Stem Cells Market Analysis, Opportunities, Trend and Forecast To 2029 Discovery Sports Media - Discovery Sports Media - January 20th, 2022
- EDUCATION SPOTLIGHT: Florida Tech Highlights Work Done During 2021 as We Enter the New Year - SpaceCoastDaily.com - January 5th, 2022
- Roundtable Discussion: Shain Looks at the Role of Transplant Eligibility in Patients With Newly Diagnosed Multiple Myeloma - Targeted Oncology - November 8th, 2021
- Brainstorm Cell, (BCLI) falls 0.65% in Active Trading on October 25 - Equities.com - October 28th, 2021
- Global Mesenchymal Stem Cells Market Prospects, Upcoming Trends and Competitive Outlook till 2028 | Lonza, Thermo Fisher, Bio-Techne, ATCC,... - October 28th, 2021
- Faster healing of wounds can decrease pain and suffering and save lives - WWNY - October 5th, 2021
- US FDA Approves Kite's Tecartus as the First and Only Car T for Adults With Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia | DNA RNA and... - October 5th, 2021
- Times really up! FDA authority to crack down on regenerative medicines upheld as grace period ends - JD Supra - July 21st, 2021
- Animal Stem Cell Therapy Market Size, Industry Analysis, Growth Factors, Trends, and Regional Forecast to 2027 - The Courier - March 11th, 2021
- An 8-year-olds search for bone marrow match in battle with leukemia comes to North Texas - The Dallas Morning News - March 11th, 2021
- Eirion Therapeutics, Inc. Closes $40 Million Series A Investment and Licensing Deal with Shanghai Haohai Biological Technology Ltd. - PRNewswire - March 11th, 2021
- How soon will COVID-19 vaccines return life to normal? - Science Magazine - February 16th, 2021
- Keep it Flowing: Combating COVID-19 Blood Shortages in Cancer Treatment - Curetoday.com - February 16th, 2021
- FL Doctors Make Breakthrough Using Stem Cells to Treat ... - February 2nd, 2021
- This Guy Injected His Dick With Stem Cells to Try to Make ... - February 2nd, 2021
- 10 Best Stem Cell Beauty Products On The Market Today - February 2nd, 2021
- HealthLynked's The Future of Healthcare Summit Brings Healthcare Experts and Technology Innovators from Around the World to Naples, Florida -... - February 2nd, 2021
- SpaceX Cargo Dragon Returning To Earth; First U.S. Commercial Cargo Craft To Return From ISS - Science Times - January 8th, 2021
- Buoyed by study, scientists increasingly hopeful first two COVID-19 vaccines effective against new strains - The Boston Globe - January 8th, 2021
- Flavors added to vaping devices damage the heart, vanilla custard the most toxic of all - Study Finds - December 23rd, 2020
- Flavours added to vaping devices can damage the heart: Study - Sify News - December 12th, 2020
- Jabbed for a good cause: Hundreds already getting COVID-19 shots as part of clinical trial - The West Volusia Beacon - August 29th, 2020
- Hesperos demonstrates innovative Human-on-a-Chip approach to modeling innate immune system response following tissue damage and acute inflammation -... - June 8th, 2020
- Hesperos Human-on-a-Chip System Used to Model Preclinical Stages of Alzheimers Disease and Mild Cognitive Impairment - Yahoo Finance - June 4th, 2020
- Can genetics explain the degrees of misery inflicted by the coronavirus? - Genetic Literacy Project - April 21st, 2020
- Beating cancer by taking the unbeaten path | ASU Now: Access, Excellence, Impact - ASU Now - April 9th, 2020
- Reviewing CRYO-CELL International (OTCMKTS:CCEL) and Harsco (OTCMKTS:HSC) - Redmond Register - March 26th, 2020
- Head to Head Analysis: Harsco (NYSE:HSC) & CRYO-CELL International (NYSE:CCEL) - Redmond Register - March 24th, 2020
- Reviewing Harsco (NYSE:HSC) and CRYO-CELL International (NYSE:CCEL) - Redmond Register - March 12th, 2020
- Data On Enlivex's Allocetra-OTS Immunotherapy for Peritoneal Solid Tumors and for Prevention of GvHD Selected for Presentation at the Transplantation... - February 24th, 2020
- Consistent Outcomes Using Ryoncil as First-Line Treatment or Salvage Therapy in 309 Children With Steroid-Refractory Acute GVHD - BioSpace - February 24th, 2020
- NASA to send equipment to International Space Station to research Improving Shoes, Showers, 3D Printing - Clarksville Online - February 24th, 2020
- Here are all the science projects that SpaceX will deliver to the ISS - Digital Trends - February 24th, 2020
- 34 years with a new heart and counting - MDJOnline.com - February 24th, 2020
- 'Florida cold' and the semi-glamorous world of work trips - CT Insider - February 19th, 2020
- 34 Years with a New Heart and Counting | 90.1 FM WABE - WABE 90.1 FM - February 19th, 2020
- Study shows how a tiny and strange marine animal produces unlimited eggs and sperm over its lifetime - National Institutes of Health - February 16th, 2020
- Research - Florida Stem Cell Research - January 3rd, 2020
- Florida Stem Cell Treatment Center - January 3rd, 2020
- Advances In Treatment Of Soft Tissue Injuries (Video) - South Florida Reporter - January 3rd, 2020
- Explained: What is the water crisis Southwest Florida is battling? - Wink News - December 24th, 2019
- Mum shares heartbreaking photo of toddler sobbing through gruelling cancer treatment - The Sun - December 1st, 2019
- World AIDS Day 2019: Theme, History and Facts about HIV and AIDS - Newsweek - December 1st, 2019
- Tulane team researching ways to end opioid addiction - News from Tulane - November 24th, 2019
- Improve global wellbeing with a degree in public health - Study International News - November 12th, 2019
- Fate Therapeutics Announces Six Presentations at the 2019 ASH Annual Meeting - GlobeNewswire - November 12th, 2019
- Reviewing US Stem Cell (OTCMKTS:USRM) and Auxly Cannabis Group (OTCMKTS:CBWTF) - Riverton Roll - November 12th, 2019
- Bloomington Vet Joins Study For Stem Cell Therapy To Treat Dogs With Arthritis - WGLT News - October 24th, 2019
- Brooks Koepka Withdraws in Korea After Reaggravating Knee Injury - Golf Channel - October 24th, 2019
- Walking in His Shoes - Curetoday.com - October 5th, 2019
- The Real Problem With Beef - The New York Times - October 2nd, 2019
- Stem Cell Treatment Clinic St. Augustine - Florida Stem Cell - March 17th, 2019
- Stem Cell Questions - Florida Stem Cell - FAQs - February 2nd, 2019
- Stem Cell Procedure for Erectile Dysfunction - January 26th, 2019
- Stuart Florida Stem Cells | NovaGenix - January 18th, 2019
- Stem Cell Hair Treatment for Hair Loss | Stem Cell Hair Growth - January 3rd, 2019
- South Florida Stem Cell Center | Melvin M. Propis, M.D. - December 11th, 2018
- Florida Stem Cell Treatments - Regenerative Orthopedic ... - December 11th, 2018
- Florida - Stem Cells Transplant Institute - July 24th, 2018
- FDA: Florida Stem Cell Clinic Violates Law | Health News ... - October 18th, 2017
- Stem cell research | UF Health, University of Florida Health - October 18th, 2017
- FDA: Serious Problems at Florida Stem Cell Clinic - WebMD - August 29th, 2017
- FDA Cracks Down On Stem-Cell Clinics Selling Unapproved Treatments - KRCB - August 29th, 2017
- US FDA steps up scrutiny of stem cell therapies - Reuters - August 29th, 2017
- Paralyzed After Pool Accident, Student Heads Back To College - News Talk Florida - August 29th, 2017
- SpaceX to Launch NASA Cargo, Try Rocket Landing Today: Watch It Live - Space.com - August 16th, 2017
- Dragon Splashes Down to Complete Resupply Mission - Space Daily - July 7th, 2017