Search

Human amnion epithelial (hAE) stem cell transplant significantly improves phenotype and survival in a murine model of intermediate maple syrup urine disease (iMSUD)

MSUD (OMIM 248600) is a rare disorder of branched chain amino acid (BCAA; leucine, isoleucine, valine) catabolism caused by mutation of the branched-chain keto-acid dehydrogenase (BCKDH) enzyme complex. Treatment requires lifelong dietary restriction and compliance is variable, often resulting in catabolic crisis. Liver transplantation has greatly improved patient outcome. Previous studies verified that hepatocyte transplantation partially corrects a transgenic murine model of iMSUD, establishing that a small number of proficient cells transplanted into the liver significantly improves disease phenotype and survival (Mol. Ther. 2009, 17(7):126; Biochim Biophys Acta 2009, 1792(10):1004). Applying this rationale, human placental amnion-derived stem cells, which share many characteristics with pluripotent embryonic stem cells, were explored as an alternative to hepatocytes for use in cell transplant. During the first 10 days of life (DOL), neonates were given two direct hepatic injections of 1x10 6cells. After 21 DOL, bi-weekly injections (2x10^6 cells) were administered until 35 DOL. Growth of transplanted iMSUD mice mimicked wildtype, and survival was significantly lengthened compared to untreated iMSUD. BCKDH enzyme activity was significantly improved, as well as serum and brain amino acids, at 35 and 100 DOL. A ratio of BCAA to alanine, a more representative indicator of disease status than BCAAs alone, was decreased >50% at both time points while alloisoleucine was not statistically different from unaffected controls. Neurotransmitter alterations and brain injury is characteristic of MSUD resulting from toxic accumulation of BCAAs. Importantly, brain monoamines showed improvements in hAE transplanted animals at both time points, and dopamine and serotonin turnover was normalized at 100 days. Similar to mouse hepatocytes, transplants of human AE stem cells partially corrected this mouse model of iMSUD. We propose that these placental stem cells may be an alternate to hepatocytes as therapy for MSUD, and possibly other liver-based inborn errors of metabolism.

Kristen Skvorak(1), Kenneth Dorko(1), Fabio Marongiu(1), Veysel Tahan(1), Marc Hansel(1), Roberto Gramignoli(1), Erland Arning(2), Teodoro Bottiglieri(2), Qin Sun(3), K. Michael Gibson(4), Stephen Strom(1)

1 Pathology, University of Pittsburgh, Pittsburgh, PA;
2 Institute of Metabolic Disease, Baylor Research Institute, Dallas, TX;
3 Human & Molecular Genetics, Baylor College of Medicine, Houston, TX;
4 Biological Sciences, Michigan Tech University, Houghton, MI, United States


Source: Cell Transplant Society - http://tinyurl.com/3ntymna

Melvin Carruth

This letter is a tribute to my brother Melvin Carruth! We believe he is one of the oldest living African Americans with Maple Syrup Urine Disease.

Read More

NBS-MSUD Connect: Your One-Stop Shop For MSUD Resources

NBS-MSUD Connect was launched as part of the Newborn Screening Connect patient registry (NBS Connect) in 2013 through a partnership between the Department of Human Genetics at Emory University, the Maple Syrup Urine Disease (MSUD) Family Support Group and other key stakeholders.

Read More

Cambrooke Therapeutics

Cambrooke Therapeutics continues to expand its line of delicious and nutritious low protein foods to help improve the lives of individuals with Inborn Errors of Metabolism such as MSUD.

Read More

Updates To Nutrition Management Guidelines

The Nutrition Management Guideline for MSUD was first published in 2014. Since that time, there have been reports of new research and experiences that have prompted updates of the guideline.

Read More

Emory Metabolic Camp 2018 Announcement

Join us June 18-23, 2018 for the 24th Annual Metabolic Camp at Emory University in Atlanta, GA!

Read More

From The Chairman’s Desk

As I sit here reflecting on how much the care and treatment of MSUD has changed over the years, my mind goes back to 1978 when our son Keith was born.

Read More

MSUD Advocacy Report

Medical Nutrition Equity Act

The Medical Nutrition Equity Act (MNEA) would require all private insurance plans (state regulated or self-insured/self-funded) and federal health programs, including Children’s Health Insurance Program, Tricare, Medicaid, Medicare, and Federal Employee Health Benefit Plans, to provide coverage for formula and low-protein foods for all children and adults with MSUD.

Read More

The MSUD Family Support Group Is Excited To Announce Their Participation In The Million Dollar Bike Ride

The MSUD Family Support Group is excited to announce their participation in The Million Dollar Bike Ride

Read More

19th Biennial MSUD Symposium

I can’t believe that almost two years have passed and it is time for another MSUD Symposium! I am especially excited about this conference because I’ve built in extra time for social interaction.

Read More

Change the lives

of MSUD adults and children

Subscribe to our mailing list

Signup To Our Newsletter Signup with your email address to receive news and updates