Bone Marrow Transplant Scientific Meeting:

Forging Ahead by Exploring Potential Treatments

What are bone marrow and stem cells?

In the center of our bones, we have marrow that contains special cells known as stem cells. Stem cells can divide to form more stem cells, or they can mature into cell types found in all of the organs of our bodies, such as those cells making up our blood vessels.

What is bone marrow transplantation?

Bone marrow transplantation (BMT) is a procedure in which a child’s own bone marrow cells are replaced with new bone marrow stem cells (a transplant) from a healthy donor. While the ideal donor is an identical twin, Progeria children could potentially receive transplants from a relative with a close match to their own cells, or even someone who is unrelated.

For cancer treatment, doctors use radiation and chemotherapy before bone marrow transplantation. Would that be a part of this treatment for Progeria?

For cancer, this type of “pretreatment” is needed to kill off as many of the cancer cells as possible. We do not need to get rid of the Progeria cells, so we would not expect to use the same type of pretreatment for BMT in Progeria. However, there would be a milder form of pretreatment to help the child with Progeria to receive cells from the donor without reacting against them. Therefore, there is some risk involved in this type of treatment. That is why it is very important to do as much research as possible before potentially moving to treatment in Progeria children.

Are we moving forward with bone marrow transplantation in children with Progeria, or are we going to work in animal models first? Here’s what the experts at our meeting recommended:

The first step for safe and effective treatment is to perform BMT in animals, such as mice, that have been created to mimic the disease process in Progeria as closely as possible. Many laboratories in the scientific community are working hard to create these animal models (some of which are funded by PRF.) The experts who attended this meeting all agreed that PRF needs to move as quickly as possible to test BMT as a treatment in Progeria mice. This will help to answer two key questions: 1) Is this procedure safe? and 2) Will the bone marrow/stem cells go to the organs in which they are most needed – the blood vessels, heart, fat stores, etc. – to replace unhealthy cells? In the coming months, PRF will promote the research that is essential to understanding whether BMT will improve the lives of children with Progeria. This workshop provided a great starting point.

Workshop Agenda & Speakers

Session One: Clinical and Genetic Aspects of HGPS

Clinical overview of HGPS and longitudinal assessment strategies: How will we know if the treatments are improving disease?

The HGPS gene defect and what it means: Putativedisease mechanism and senescence characteristics

Metabolic correction of Mucopolysaccharidosis Disorders by bone marrow transplantation and gene therapy

BMT strategies in osteogenesis imperfecta: Clinical trials and lessons learned

Transplantation experiences with storage diseases that may apply to HGPS

Session Three: Evidence For / Against Vascular Repopulation Leading to Clinical Improvement

Chairs: Elizabeth Nabel, MD and Donald Orlic, PhD
Associate Investigator, Genetics and Molecular Biology Branch,
NHLBI, Bethesda, MD

Vascular wall cell recruitment and BMT: How might transplant affect vascular plaques?

Potential for cardiovascular repopulation with BMT in Progeria – evidence from human and mouse studies

The state of funding for Hutchinson-Gilford Progeria Syndrome from the National Institute on Aging

Early and late risks of hematopoietic cell transplants vs disease control

What can we learn from stem cell transplants to correct other genetic disorders?

Umbilical cord blood transplantation; results from prior studies and assessment of this strategy for Progeria

Selected Participant Comments:

"A very impressive group of experts was assembled, and the quality of the scientific discussion was very high. I learned a lot about the pros and cons of bone marrow transplantation for other genetic disorders, and how that experience might extrapolate to Hutchinson-Gilford Progeria Syndrome.”

Francis Collins, MD, PhD, Director of the
National Human Genome Research Institute

"I thoroughly enjoyed participating in this workshop. The greatest strength was that the diverse group enabled us to address most aspects of Progeria in a concise and informative manner. My congratulations for assembling such an outstanding group.”

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