A first-in-human study at Cincinnati Children’s suggests that a novel cell therapy could correct telomere shortening in patients with telomere biology disorders (TBDs) such as dyskeratosis congenita. The therapy involves exposing a patient’s hematopoietic stem cells to a viral vector ex vivo, then reinfusing the treated cells into the patient.

Kasiani Myers, MD, a pediatric hematologist at Cincinnati Children’s, is the principal investigator for the study, which is sponsored by Elixirgen Therapeutics. In December 2022, Myers presented the study’s initial findings at the 64th American Society of Hematology (ASH) Annual Meeting in New Orleans.

A Possible Alternative to Bone Marrow Transplantation

Telomeres cap and protect chromosomes and are required for cell division and blood production. TBDs, including dyskeratosis congenita, eventually affect most organs, and patients are highly predisposed to bone marrow failure and certain cancers. The only approved curative therapy is a bone marrow transplant. Myers notes that patients with TBDs are highly sensitive to radiation and chemotherapy, which adds urgency to the quest for a less toxic treatment approach. 

The novel treatment is designed to elongate telomeres, not correct genetic defects associated with TBDs. It is genotype and mutation-independent, meaning it could be used for all genetically driven types of these diseases. That’s important, Myers says, since more than 15 genes are implicated in telomere maintenance, and many patients lack a known mutation.

Telomeres Elongate, CD34+ Cells Maintain Full Differentiation Potential

In the study, researchers collected CD34+ hematopoietic stem cells from an adult patient with dyskeratosis congenita in February 2022. They exposed the cells to a viral vector encoding ZSCAN4, a protein that regulates telomere elongation and enhances genome stability. Exposure increased the telomere length of the CD34+ cells ex vivo by 1.24-fold, bringing them into the healthy control range.  

The differentiation potential of the CD34+ cells did not change after exposure. This suggests the cells could successfully restore hematopoiesis in vivo—an exciting discovery since CD34+ stem cells give rise to all hematopoietic cells in the body.  

The treated cells were ready for reinfusion in about two days. Afterward, the results of testing suggested an emerging population of cells with longer telomeres in vivo. 

No acute or long-term adverse effects were observed in the patient for nine months following treatment. 

Exploring the Therapy’s Longer-Term Effectiveness 

In the study’s next phase, Myers and her team will explore the durability of this therapy and whether bone marrow function improves over time in treated patients. Ideally, she says, patients would require only one round of treatment to avoid the bone marrow failure inherent to TBDs.

This adult-only study is currently open and enrolling additional participants. To learn more or inquire about enrolling a patient, please email Kasiani.Myers@cchmc.org.