Advancing Care of a Devastating Disease Through Gene Therapy

Mucopolysaccharidosis type 1, also known as Hurler syndrome, is a rare but life-threatening genetic condition. Babies born with this inherited disorder do not produce an enzyme needed to break down complex sugars in the body, affecting development of the brain, bones, liver and other vital organs.

The accepted standard of care for Hurler syndrome is a bone marrow transplant (BMT) from a well-matched donor. While BMT is effective at preventing neurocognitive decline in Hurler syndrome patients, it cannot stop progressive damage to other parts of the body like the skeleton, eyes and heart. BMT replaces unhealthy white blood cells with healthy enzyme-producing white blood cells, but achieving this positive result requires a suitably matched donor. Locating such a donor can prolong time until treatment, allowing the disease to progress unchecked and decreasing the overall benefit of transplant. In addition, some patients lack suitably matched donors.

Additionally, enzyme replacement therapy (ERT) can help alleviate some symptoms of the disease. Since the underlying cause of Hurler syndrome is a lack of the lysosomal enzyme that breaks down glycosaminoglycans, ERT helps break down these compounds in the body. However, ERT cannot provide enzyme across the blood-brain barrier to reach the brain where it is needed to prevent damage to the developing brain. As a result, ERT cannot address brain function, leaving patients at risk for neurocognitive decline, which leads to intellectual disability.

To avoid the obstacles of BMT and ERT, gene therapy presents a novel approach to conquering Hurler syndrome. A new international trial is investigating the efficacy and safety of gene therapy in patients with Hurler syndrome and will compare results of gene therapy against BMT which is the current standard of care. UCSF Benioff Children’s Hospitals are among three sites in the U.S. and seven in the world now enrolling patients for the clinical trial.

For those receiving gene therapy in the trial, the patients serve as donors for themselves, supplying the needed stem cells, which are then gene-corrected in the laboratory before being re-infused into the patients.

“Gene therapy may have significant advantages over standard BMT,” said pediatric hematologist-oncologist Sandhya Kharbanda, MD, professor of pediatrics and medical director of the BMT program at UCSF Benioff Children’s Hospital San Francisco. “It negates the need for an outside donor since patients serve as donors for themselves and it eliminates some serious risks of transplant that are associated with standard BMT, particularly with the use of a mismatched donor.”

Promising early results

Although this trial has recently gotten underway, an eight-patient pilot study in Italy demonstrated promising clinical outcomes that seem superior to BMT. Kharbanda anticipates the larger trial underway at UCSF Benioff Children’s Hospitals will solidify those results.

“Based on the preliminary data, this will likely be a major step forward for these patients,” she said. “In the pilot trial, the patients had very high level of enzyme production – higher than with the standard-of-care BMT. It seems from both a donor standpoint and therapeutic standpoint, gene therapy may be a more effective therapeutic option.”

The trial will enroll patients as young as 28 days and up to 30 months. Early diagnosis of Hurler syndrome has improved, thanks to newborn screening adopted by California and several other states, allowing patients to receive treatment before the disease can advance and affect brain development and other organs and bodily systems. 

The researchers hope to have results within two years after treatment with the gene therapy and they will follow the patients annually for an additional five years. 

“The goal is to ensure young patients not only survive the transplant process,” Kharbanda said, “but also have a long lifespan with maximum function, reach important childhood milestones, develop a normal IQ and enjoy a high quality of life.”

Refer a patient online or call the Pediatric Access Center at (877) 822-4453 (877-UC-CHILD). 
 

About UCSF Health: UCSF Health is recognized worldwide for its innovative patient care, reflecting the latest medical knowledge, advanced technologies and pioneering research. It includes the flagship UCSF Medical Center, which is a top-ranked specialty hospital, as well as UCSF Benioff Children’s Hospitals, with campuses in San Francisco and Oakland, Langley Porter Psychiatric Hospital and Clinics, UCSF Benioff Children’s Physicians and the UCSF Faculty Practice. These hospitals serve as the academic medical center of the University of California, San Francisco, which is world-renowned for its graduate-level health sciences education and biomedical research. UCSF Health has affiliations with hospitals and health organizations throughout the Bay Area. Visit www.ucsfhealth.org. Follow UCSF Health on Facebook or on Twitter.