International Center for Polyamine Disorders

The International Center for Polyamine Disorders (ICPD) is a collaborative translational and clinical research program operated under the auspices of Michigan State University and Spectrum Health West Michigan in Grand Rapids, Michigan. The ICPD launched in summer 2020 and includes a polyaminopathy patient biobank, a state-of-the-art translational research lab core and a clinical genetics team at Spectrum Health West Michigan. The ICPD offers innovative ways to study polyaminopathies, associated disabilities and develop strategies for treatment and prevention. This collaborative effort between Spectrum Health and Michigan State University brings world leading experts in the field from the bench and clinic together to study these rare genetic diseases.

The ICPD is led by:

  • Caleb Bupp

    Caleb Bupp, MD, FACMG, Clinical Director ICPD, Section Chief – Medical Genetics and Genomics at Helen DeVos Children’s Hospital

  • Surender Rajasekaran

    Surender Rajasekaran, MD, Research Director ICPD, Medical Director of Research at Spectrum Health West Michigan

  • Andre Bachmann

    Andre Bachmann, PhD, Scientific Director ICPD, Professor, Associate Chair for Research in the Department of Pediatrics and Human Development and Michigan State University faculty

  • Charles Schwartz

    Charles E. Schwartz, PhD, former Director of Research, JC Self Research Institute, Greenwood Genetic Center and Adjunct Professor, Department of Pediatrics and Human Development, Michigan State University


The Bupp/Bachmann team was able to demonstrate that both fibroblasts and red blood cells from a Bachmann-Bupp Syndrome (BABS) patient have exceptionally high ODC (ornithine decarboxylase) enzyme levels and resulting abnormal polyamine levels due to a gain of function mutation in the ODC1 gene. Consequently, patients with the  Bachmann-Bupp Syndrome could benefit from an FDA-approved drug called DFMO (an ODC inhibitor). These latest data were reported in a follow-up report by Schultz, Bupp, Rajasekaran and Bachmann in the Biochemical Journal [3]. DFMO is currently in use for the treatment of African sleeping sickness and in clinical trials as a chemopreventive and anticancer agent against several cancers including neuroblastoma[4-6]. There are now at least eight additional worldwide cases of the Bachmann-Bupp Syndrome and Drs. Bachmann and Bupp are consulted throughout the world for their expertise.

Before the discovery of the Bachmann-Bupp Syndrome, there was one other known polyamine disorder, Snyder-Robinson Syndrome (SRS). This condition results from mutations in the spermine synthase gene (SMS) and was first discovered in 2003. It also results in abnormalities of polyamine levels. There are now approximately 65 males with SRS worldwide. The ICPD will serve as a center for clinical evaluation and research for SRS.

There are also two other newer conditions in the polyamine pathway (pending publication). There are at least 20 potential conditions in the polyamine pathway and all would fall under the umbrella of the ICPD scope of work.

The ICPD is headquartered in Grand Rapids, Michigan and serves as the worldwide nexus for comprehensive data/sample collection and scientific information about polyamine-associated diseases. ICPD has strong ties and collaborates with the Greenwood Genetic Center in South Carolina and the Snyder-Robinson Foundation.

For general inquiries about the ICPD, please contact the center coordinator Elizabeth VanSickle: Elizabeth.vansickle@helendevoschildrens.org.

For clinical inquiries, contact the ICPD genetic counselor Julianne Michael, MS, CGC: Julianne.michael@spectrumhealth.org.

For phone inquiries, call 616.486.8646.

References

  1. Bupp CP, Schultz CR, Uhl KL, Rajasekaran S, Bachmann AS. Novel de novo pathogenic variant in the ODC1 gene in a girl with developmental delay, alopecia, and dysmorphic features. Am J Med Genet A. 2018;176(12):2548-2553. PMID: 30239107

  2. Bachmann AS, Geerts D. Polyamine Synthesis as a target of MYC oncogenes. J Biol Chem. 2018;293(48):18757-18769. PMID: 30404920

  3. Schultz CR, Bupp CP, Rajasekaran S, Bachmann AS. Biochemical features of primary cells from a pediatric patient with a gain-of-function ODC1 genetic mutation. Biochem J. 2019;476(14):2047-2057. PMID: 31249027

  4. Priotto G, Kasparian S, Mutombo W, Ngouama D, Ghorashian S, Arnold U, Ghabri S, Baudin E, Buard V, Kazadi-Kyanza S, Ilunga M, Mutangala W, Pohlig G, Schmid C, Karunakara U, Torreele E, Kande V. Nifurtimox-eflornithine combination therapy for second-stage African Trypanosoma brucei gambiense trypanosomiasis: a multicentre, randomised, phase III, non-inferiority trial. Lancet. 2009;374(9683):56-64. PMID: 19559476

  5. Saulnier Sholler GL, Gerner EW, Bergendahl G, MacArthur RB, VanderWerff A, Ashikaga T, Bond JP, Ferguson W, Roberts W, Wada RK, Eslin D, Kraveka JM, Kaplan J, Mitchell D, Parikh NS, Neville K, Sender L, Higgins T, Kawakita M, Hiramatsu K, Moriya SS, Bachmann AS. A Phase I Trial of DFMO Targeting Polyamine Addiction in Patients with Relapsed/Refractory Neuroblastoma. PLoS One. 2015;10(5):e0127246. PMID: 26018967

  6. Saulnier Sholler GLS, Ferguson W, Bergendahl G, Bond JP, Neville K, Eslin D, Brown V, Roberts W, Wada RK, Oesterheld J, Mitchell D, Foley J, Parikh NS, Eshun F, Zage P, Rawwas J, Sencer S, Pankiewicz D, Quinn M, Rich M, Junewick J, Kraveka JM. Maintenance DFMO Increases Survival in High Risk Neuroblastoma. Sci Rep. 2018;8(1):14445. PMID: 30262852