On January 7, a 57-year-old male patient received a genetically-modified pig heart transplant at the University of Maryland Medical Center (UMMC). The surgery was a world-first and deemed the patients only chance for survival after he was declared unsuitable for a human donor transplant or an artificial heart pump. On January 10, the University of Maryland School of Medicine (UMSOM) published a news release stating that the patient was doing well, and is being carefully monitored over the next days and weeks to determine whether the transplant provides lifesaving benefits.
Dr. Bartley P. Griffith the surgeon responsible for transplanting the porcine heart into the patient and a professor in transplant surgery at UMSOM said, We are proceeding cautiously, but we are also optimistic that this first-in-the-world surgery will provide an important new option for patients in the future. Dr. Griffith leads the Cardiac Xenotransplantation Program at UMSOM alongside Dr. Muhammad M. Mohiuddin, professor of surgery at UMSOM.
The operation at the UMMC is an example of xenotransplantation. Xenotransplantation refers to any procedure involving the transplantation, infusion or implantation of cells, tissue or organs from a nonhuman, animal source into a human.
While the surgery was the first-of-its-kind, the concept of xenotransplantation is not novel. Chris Denning, professor of stem cell biology at the University of Nottingham told the UK Science Media Centre, Only in the late 1990s did the technologies become available and have steadily been improved ever since. Various academic and industrial teams have worked in this area for over 20 years, so it is not surprising that this has now been tested.
In the 20th century, non-human primates (NHP) were explored as potentially suitable donors for xenotransplantation due to the genetic similarities between primates and humans. However, concerns such as ethical issues, transmission of infection across species and breeding difficulties halted this research. Consequently, pigs are now considered to be the most appropriate candidate species for xenotransplantation.
"Pigs are considered for several reasons, Denning said. The size and anatomy of the pig heart is roughly the same as a humans, though there are considerable differences:
He added that, despite public perception, it is also relatively easy to keep pigs in a sterile condition.
Despite these advantages, transplanting a porcine heart into a human is considerably more challenging than transplanting a human heart. There are genetic differences between pigs and humans, which can lead to immunological rejection of the organ. Pigs have a gene that produces a molecule called (1,3)galactosyl transferase, which humans do not. This triggers an immediate and aggressive immune response, called hyperacute rejection, said Denning, ultimately causing the body to reject the organ.
The xenotransplantation conducted at UMMC involved a pig that had reportedly received 10 genetic modifications in total. Its unclear at this stage exactly what genes were modified, however the news release from UMSOM states three genes responsible for rapid antibody-mediated rejection of pig organs by humans were knocked out in the pig, and six human genes responsible for immune acceptance were inserted. An additional gene was also knocked out to stop excessive growth of the heart tissue.
Knockout means that an organism has been genetically altered such that it lacks either a single base, a whole gene or several genes. Often, genetic knockouts are utilized in laboratory research to understand how certain genes function, by monitoring changes in the organism when the gene is not expressed.
The porcine heart was provided by Revivicor, a subsidiary of United Therapeutics. You might recall Revivicor as the spin-out company of PPL Therapeutics, the UK-based biotech firm behind the first cloned mammal, Dolly the sheep. In December 2021, Revivicor also supplied New York University Langone Health with a kidney from a genetically-modified pig for an investigational procedure in a deceased human donor. The donor remained on ventilator support, and was closely monitored throughout the procedure and a subsequent observation period, during which the researchers said there were no signs of rejection.
According to the UMSOM news release, it received a $15.7 million research grant to evaluate Revivicor genetically-modified pig UHearts in baboon studies. Mohiuddin and colleagues reportedly applied for permission to conduct human clinical trials of the porcine heart from the US Food and Drug Administration (FDA), but were rejected. Under normal circumstances, IMPs must be evaluated in animal studies prior to human clinical trials this is standard protocol.
However, in the instance of the 57-year-old patient, an exception was made. The FDA granted emergency authorization for the procedure under its expanded access provision. This allows for an individual to access an investigational medicinal product (IMP) outside of clinical trials when there is no alternative therapy option available.
Will it be successful? asked Denning. The fact that the human patient is alive after a few days indicates that immediate hyperacute rejection has been avoided, which is the first hurdle. Only time will tell whether there are issues with chronic rejection, caused by e.g., incompatibility of major and minor histocompatibility complexes. Continuous monitoring will be needed to monitor transmission of potential pathogens, such as porcine endogenous retroviruses or hybrid porcine/human endogenous retroviruses.
Should the patient survive and the xenotransplant prove successful, it will likely raise a lot of questions as to how regulatory bodies move forward. Individual emergency authorization procedures do not generate sufficient data for the widespread implementation of xenotransplantation clinical trials are crucial for demonstrating efficacy.
However, there are logistical hurdles associated with even trialing the procedure. Seventeen people die every day waiting for an organ transplant, according to the Health Resources & Services Administration. There is a severe shortage of organs, and a steep decline in donation has been observed during the COVID-19 global pandemic. While a proposed advantage of xenotransplants is that they could provide on-demand organs, the procedure and its unknowns make it a very high-risk surgery. How does a clinician, or regulatory body, decide that a patient has waited long enough for a human organ that they qualify for inclusion in a trial?
Furthermore, if xenotransplant clinical trials support widespread adoption of xenotransplant procedures, how do we regulate a system whereby organs are widely available? Policies on patient selection and organ allocation currently exist in healthcare systems across the world. Navigating changes to these policies will require global conversations across different regulatory bodies.
Finally, a hurdle that Denning said could be the biggest of them all is: What do the general public think? Is it acceptable to harvest organs from animals? One thing that is for sure, is the outcomes of this [patient] will be watched closely by many, Denning concluded.
Read more:
- Signal of Benefit for Stem Cell Therapy in Progressive MS - Medscape - March 7th, 2024
- The Controversies Surrounding Stem Cell Therapy for Autism - The Portugal News - February 24th, 2024
- Benefits of Stem Cell Therapy - News Channel 5 Nashville - February 7th, 2024
- What is Stem Cell Therapy & How It Helps Others - Publicist Paper - January 31st, 2024
- A guide to stem cell therapy in Thailand - Thaiger - January 4th, 2024
- Half of pediatric patients with aHUS benefit from Soliris after... - AHUS News - December 21st, 2023
- Real world analysis on the determinants of survival in primary ... - Nature.com - December 5th, 2023
- The Best Beauty Gifts According To People Who Really Know Skin Care - HuffPost - December 5th, 2023
- The Eyepopping Factory Construction Boom in the US - WOLF STREET - December 3rd, 2023
- Benefit of Neoadjuvant Therapy Illustrated During ESMO Congress ... - Targeted Oncology - December 1st, 2023
- Benefits Outweigh Risks as FDA Inspects CAR-T Cell Therapy ... - Curetoday.com - December 1st, 2023
- Review What Real Cavityn Customers Say About Benefits and Side ... - Seattle Weekly - December 1st, 2023
- 'There is a Scientific Fraud Epidemic' - Slashdot - Slashdot - December 1st, 2023
- 15 Best Hydrating Serums to Soothe Any Skin Type 2023 - Town & Country - December 1st, 2023
- Innovations in Cosmetic Dermatology: A Glimpse into the Future - APN News - December 1st, 2023
- FDA Probes New Cases of Cancer That May Stem From Cancer Cell ... - MedCity News - November 29th, 2023
- Use of plant stem cells in topical formulations on the rise - CosmeticsDesign.com USA - November 29th, 2023
- Stem cell-based treatment controls blood sugar in people with Type ... - EurekAlert - November 29th, 2023
- Biologics Market is projected to grow at a CAGR of 8.5% by 2034: Visiongain - Yahoo Finance - November 29th, 2023
- Scientists devise new technique that can pinpoint the causes and ... - EurekAlert - November 29th, 2023
- Global Advanced Therapy Medicinal Products Market is on the brink ... - PharmiWeb.com - November 29th, 2023
- Introducing Orgavalue - The 2023 EIT InnoStars Awards winner - EU-Startups - November 29th, 2023
- Episode 160: Euan Ashley discusses precision medicine and the ... - IHMC - November 29th, 2023
- Is Phenq Right For You? Review The Facts Before Making a ... - Vashon-Maury Island Beachcomber - November 27th, 2023
- Cavityn Reviews - Does It Work? Cheap Scam or Effective ... - The Daily World - November 25th, 2023
- Trend Hunting With Beautystreams At Cosmoprof Asia 2023 - BeautyMatter - November 25th, 2023
- FDA Considers First CRISPR Gene Editing Treatment That May ... - Slashdot - November 25th, 2023
- How Do Plants Determine Where the Light Is Coming From? - Lab Manager Magazine - November 25th, 2023
- Deaths From Coal Pollution Have Dropped, But Emissions May be ... - Slashdot - November 25th, 2023
- Stem cell-based therapies for stroke in newborns - Cochrane - November 23rd, 2023
- Dr Leslie on Outpatient CAR T-Cell Therapy Programs for ... - OncLive - November 23rd, 2023
- Human Milk-Based Therapy May Be Beneficial in Blood Cancers - Curetoday.com - November 23rd, 2023
- Oncological Horizons: The Synergy of Medical and Surgical ... - Cureus - November 23rd, 2023
- Human and environmental safety of carbon nanotubes across their ... - Nature.com - November 23rd, 2023
- Immix Biopharma to Host KOL Event to Discuss its BCMA-Targeted ... - BioSpace - November 23rd, 2023
- #HearTheMarsdenKids call on NHS London to reconsider cancer ... - Metro.co.uk - November 23rd, 2023
- Diagnosis and Management of Cardiovascular Risk in Patients with ... - Dove Medical Press - November 23rd, 2023
- BioLineRx Reports Third Quarter 2023 Financial Results and ... - PR Newswire - November 21st, 2023
- Why our Award Winners Beauty Box is the ultimate beauty gift (for ... - Yahoo Singapore News - November 21st, 2023
- SightCare Reviews - Is Official Website for Sight Care Legit to Try or ... - Vashon-Maury Island Beachcomber - November 21st, 2023
- Legend Biotech Reports Third Quarter 2023 Results and Recent ... - StreetInsider.com - November 21st, 2023
- Lorenzo's Oil: Can It Really Treat ALD? - Verywell Health - November 19th, 2023
- Doctor Says Living To 120 By End Of Decade Is Possible What's the Secret? - Benzinga - November 19th, 2023
- The week in pharma: action, reaction and insight week to ... - The Pharma Letter - November 19th, 2023
- Race Cannot Be Used To Predict Heart Disease, Scientists Say ... - Slashdot - November 19th, 2023
- SpaceX's Starship Reaches Outer Space Before Intentional ... - Slashdot - November 19th, 2023
- Mesenchymal Stem Cells Market is projected to reach USD 3,319 million by 2030 according to a new research r... - WhaTech Technology and Markets News - November 17th, 2023
- LMRUK: Protecting the next generation through cord blood - Charity Today News - November 17th, 2023
- Anti-aging molecule discovered that extends lifespan - Earth.com - November 17th, 2023
- Montana State researcher envisions living building materials that ... - Montana State University - November 17th, 2023
- OxyHelp Explores the Benefits of Hyperbaric Oxygen Therapy for ... - StreetInsider.com - November 15th, 2023
- Health benefits of bone marrow - Pakistan Observer - November 15th, 2023
- Evolving the standard of care: What is next for functional ... - NeuroNews International - November 15th, 2023
- Affimed Reports Third Quarter 2023 Financial Results and ... - BioSpace - November 15th, 2023
- Meet the World's First Whole-Eye Transplant Recipient - TIME - November 15th, 2023
- Calidi Biotherapeutics Reports Third Quarter 2023 Operating and ... - Business Wire - November 15th, 2023
- 10 Asia-Pacific biotech companies leading innovation in the region - Labiotech.eu - November 15th, 2023
- Fitspresso Reviews (November Update) Natural Ingredients That ... - Bainbridge Island Review - November 15th, 2023
- 2seventy bio Reports Third Quarter Financial Results and Recent ... - Business Wire - November 15th, 2023
- Japan To Create $6.6 Billion Fund To Develop Outer Space Industry ... - Slashdot - November 15th, 2023
- Be The Match, Healthcare Marketing Impact Awards 2023 - Ad Age - November 13th, 2023
- Medicare coverage saves lives. Enrolling shouldn't be this ... - Kevin MD - November 13th, 2023
- Future Ocean Foods: 36 Global Alt-Seafood Startups Form Association To Tackle Overfishing, Microplastics & More - Green Queen Media - November 13th, 2023
- Orchard Therapeutics Reports Third Quarter 2023 Financial Results ... - StreetInsider.com - November 13th, 2023
- Celebrity doctor reveals Hollywoods hidden trend of stem cell antiaging therapies - Longevity.Technology - November 11th, 2023
- Amazon Expands Healthcare Push With One Medical Benefits For ... - Slashdot - November 11th, 2023
- Bene Meat Technologies becomes the first to receive EU approval ... - Pet Food Processing - November 11th, 2023
- FDA Grants Orphan Drug Designation to MAIA Biotechnology for THIO as a Treatment for Glioblastoma - Yahoo Finance - November 11th, 2023
- MaaT Pharma Provides Third Quarter 2023 Business Update and ... - Business Wire - November 11th, 2023
- IN8bio Reports Third Quarter 2023 Financial Results and Provides ... - GlobeNewswire - November 11th, 2023
- Fast Lean Pro Reviews - Overpriced or Optimal Ingredients That ... - Journal of the San Juan Islands - November 11th, 2023
- Fate Therapeutics Reports Third Quarter 2023 Financial Results and ... - GlobeNewswire - November 11th, 2023
- Worlds first whole-eye and partial face transplant gives Arkansas man new hope - CNN - November 9th, 2023
- Glowing Fingertips And Green Eyes: First-of-Its-Kind Monkey ... - ScienceAlert - November 9th, 2023
- 10 Natural Body Scrubs That Exfoliate And Invigorate My Skin - PINKVILLA - November 9th, 2023
- CRISPR Therapeutics Provides Business Update and Reports Third ... - StreetInsider.com - November 9th, 2023
- Fate Therapeutics Reports Third Quarter 2023 Financial Results and ... - StreetInsider.com - November 9th, 2023
- Sight Care Reviews - Overpriced or Worth the Hype? SightCare Pills ... - Journal of the San Juan Islands - November 9th, 2023
- 6 Amazing Health Benefits Of Giloy (Tinospora cordifolia) - WION - November 9th, 2023
- The Global Market for Bispecific Antibody Therapeutics Contract Manufacturing 2023-2030: Driven by Demand for Innovative Therapies and Promising... - November 7th, 2023
Recent Comments