Boston Children’s Hospital has been quietly changing the future of health for every child, here and around the world, since 1869. Named the number one hospital for care in the country, we are also the largest research center for pediatric medicine anywhere. Each year the conference proceeds benefit a new research initiative at Boston Children’s Hospital, as well as unique collaborations between Boston Children’s and the Broad Institute. Since inception in 2012, the Boston Investment Conference has generated more than $22M to accelerate the most promising research aimed at better treatments for sick children in the near term.
2023 Boston Investment Conference Awardee
Therapy may lengthen human lifespan, short-circuit fatal childhood diseases
Telomeres, the genetic strands found on the tips of every human chromosome, serve as the body’s biological clocks. Telomeres naturally shorten over time as cells divide, and as they do, we age. Shorter telomeres are associated with shortened human lifespan and a number of common diseases. But children born with very short telomeres because of genetic mutations fall prey to a host of fatal diseases usually reserved for older adults, such as bone marrow failure, liver cirrhosis and pulmonary fibrosis.
Boston Children’s researcher Suneet Agarwal, MD, PhD, believes he can slow the biological clock and give these children years of their lives back.
Dr. Agarwal discovered that thymidine, a chemical compound already in trials to treat mitochondrial disease in children, appears to reverse the genetic damage associated with telomere biology disorders (TBDs). To discover this, he conducted the first genome-wide search for genes controlling human telomere maintenance and identified nucleotide metabolism as a critical pathway. Specifically, genes regulating thymidine came up as perfect targets, suggesting that manipulating thymidine might impact telomeres in human cells.
Testing his theory on embryonic-like cells derived from skin or blood of TBD patients, Dr. Agarwal found that supplementing the cultures with thymidine can regrow telomeres. That means a known drug may very well hold the key to arresting or reversing the progression of a host of fatal childhood illnesses. It also has broader implications for extending human lifespan as numerous studies have shown telomere length to be a biological foundation of aging.
To turn Dr. Agarwal’s findings into life-saving therapies, his team must:
- Pass initial regulatory clinical safety checks, though the process may be expedited because thymidine is now being tested in two other clinical trials for children for mitochondrial diseases;
- Manufacture the drug substance in a form suitable for pediatric patients and perform the required pre-clinical studies on this material; and
- Design the clinical trial and obtain U.S. Food and Drug Administration (FDA) approval.
Support from the Boston Investment Conference will enable Dr. Agarwal and his team to complete the drug manufacturing, conduct the pre-clinical studies required by the FDA, and initiate a clinical trial of thymidine in patients with TBDs within 12 to 18 months. This critical work will pave the way to new treatments and offer fresh hope for children with telomere diseases.
Suneet Agarwal, MD, PhD Co-Program Leader for the Stem Cell Transplant Center, Department of Pediatric Hematology/Oncology, Boston Children’s Hospital