At our last symposium, we were thrilled when Dr. James M. Wilson of the University of Pennsylvania’s Orphan Disease Center suggested that we work together to convene a group of researchers and clinicians involved in MSUD with the aim of identifying gaps in the research and determine priorities for moving forward. This meeting took place on June 20th in Philadelphia, and we represented the MSUD Family Support Group.
Our medical advisor, Dr. Melissa Wasserstein of Montefiore Hospital and Albert Einstein College of Medicine in New York led the meeting. Other attendees included medical advisor Dr. Can Ficicioglu, Children’s Hospital of Philadelphia, Dr. Gregory Rice, University of Wisconsin, Dr. Rakesh Sindhi, Hillman Center for Pediatric Transplantation at the University of Pittsburgh, Dr. Jonathan Beever, University of Tennessee, and Dr. Vincent Carson and Karlla Brigatti, Clinic for Special Children. Dr. Wilson was our host, and Dr. Jenny Greig, recipient of the 2018 MSUD Million Dollar Bike Ride grant, was there to present her preliminary research findings on muscle-directed gene therapy.
Another hot topic at the meeting was the possibility of using a type of gene therapy, called messenger RNA (mRNA) therapy, as a therapeutic tool. Dr. Greig is investigating the use of mRNA to target liver cells to replace the defective enzyme for metabolism of branched-chain amino acids. There is interest in determining whether mRNA can be used during a metabolic crisis to rapidly reduce leucine levels and protect the brain as well as for ongoing, daily management of MSUD.
When it was our turn to present, we noted some of the challenges to living with MSUD, which include:
- Threat of metabolic decompensation
- Inability to monitor BCAA levels regularly using a home monitor
- Determining the best diet for each individual and improving compliance
- The effect of MSUD on the brain
We noted that researchers have approached us to ask for our support with various projects, but that we’d like to drive research into areas that we feel are important.
We had a lively discussion about future research priorities, including gene therapy, the need for neuropsychological testing and quality of life studies, the need to continue the work begun at Emory on a patient registry, to work with the community to compile natural history data, and the need to collaborate with researchers and clinicians around the world.
We left the meeting feeling excited about the opportunities for further improvements in MSUD care and potential molecular therapies.