A Polyamine Story

  • A Polyamine Story by Caleb Bupp, MD

    Dr. Bupp is a Clinical Geneticist and Chief of Genetics and Genomics at Spectrum Health and Helen DeVos Children’s Center in Grand Rapids, Michigan. He completed his fellowship at the Greenwood Genetic Center from 2012-2014, where he learned about genetic conditions. During this time, he worked with Drs. Charles Schwartz and Roger Stevenson. He was aware of the SRS work, but wasn’t part of it at that time.

    While he was working at Spectrum Health, he was unaware of the polyamigo gathering for SRS at the Greenwood Genetic Center in 2017. Andre’ Bachmann was part of this meeting, and it turns out he will play an important role.

    Around the same time, he evaluated an 11-month-old baby girl in his clinic. She had developmental delay, large body, large head and lack of any hair. He decided to run Whole Exome Sequencing and found that she had a change in the ODC1 gene. At that time, there was no known disease associated with this gene. He wasn’t sure what it meant.

    Several months later, he went to a ground rounds presentation at Helen DeVos Children’s Hospital, given by Drs. Surender Rajasekaran (Dr. Raja) and Andre’ Bachmann. Dr. Raja has an interest in multi-organ dysfunction in the Pediatric Intensive Care Unit. That morning, he presented some work he had done with Andre. Andre is a world’s expert in polyamines, but nothing clicked for Dr. Bupp that day. He went back to review some of his patients’ records and realized that ODC1 went along with polyamines. It turned out, not only did ODC1 go along with polyamines, but also a polyamine world expert was just down the street! Andre is known for his work with polyamines including neuroblastoma. They combined forces to describe a new disorder called Bachmann- Bupp Syndrome (BBS). They were very excided that there was a drug called DFMO, which treated patient cells in the lab.

    Dr. Bupp refers to this story as “extreme serendipity”. Now, along with work from ODCI and SRS, the International Center for Polyamine Disorders (ICPD) was formed. This provides important opportunities for resources.

    What is happening now?

    Biobank – SRS sample transfer from Greenwood to Grand Rapids

    Prospective study – beginning to set up a study to accept new samples for SRS or BBS

    Research Studies – Andre has some excellent ideas

    Collaborations – the new ICPD will serve as a hub for collaboration and take partnerships to the next level

    Treatments – the first treatment trial for ODC1 is almost finished. They are excited to publish the results.

    Conferences

    Clinical testing

    New diagnostics and new disorders

    Access to funding – combining forces will help with funding.

    International reach – genetic conditions are everywhere!

    What else?

    He asks everyone what other things do they need to be thinking about for this new center.

About the Presenter

  • Caleb Bupp MD, FACMG is a Clinical Assistant Professor in Pediatrics and Human Development at Michigan State University and Chief of the Division of Medical Genetics and Genomics at Spectrum Health Helen DeVos Children’s Hospital in Grand Rapids.

    His clinical interests include clinical genetics, dysmorphology and the genetic causes of autism and intellectual disability. He has collaborated with Dr. Bachmann in the discovery and potential treatment of Bachmann-Bupp Syndrome and his presentation will cover the current state of knowledge of this condition in which excess putrescine is produced as a result of increased levels of ornithine decarboxylase.

    Caleb has an MD from the University of Toledo College of Medicine. He did a pediatric residency at the University of Louisville and a medical genetics residency at Greenwood Genetic Center where SRS was first shown to be due to a mutation in the spermine synthase gene.