Ayla Bashir and her parents, Sobia Qureshi and Zahid Bashir, have participated in a medical first with Ayla surviving Pompe disease. The same disease caused the death of her sisters at 8 months and 2.5 years.

An article recently published in Science describes Ayla’s physicians as using enzyme replacement therapy (ERT) during fetal development. This procedure adds a new dimension to fetal therapies.

The doctors initially administered six ERT treatments and Ayla was born full-term. The child is now receiving postnatal enzyme therapy at a hospital in Ottawa Canada. Ayla is sixteen months with normal motor function as well as meeting all developmental milestones.

About Pompe Disease

Infantile-onset Pompe disease is a lysosomal storage disease causing damage to major organs prior to birth including ventilator dependency and early death. In cases where ERT is not used, most babies die from respiratory or cardiac complications within one year.

About ERT

The ERT process consists of injecting the deficient enzyme into the patient’s bloodstream where it migrates into the deficient cells. The in-utero treatment is an extension of ERT and if given before birth can cross the brain barrier. Another factor is that damage that occured to the fetus is irreparable after birth.

Pompe disease is the result of mutations in a gene that produces acid alpha-glucosidase (GAA). The mutations prevent the body from producing enough GAA enzymes. As a result, glycogen builds up and cell damage occurs.

The body uses GAA to:

• Break down glycogen, a stored form of sugar used for energy
• GAA functions within lysosomes (cellular clearinghouses)
• Lysosomes ingest many substances including glycogen
• GAA converts glycogen into glucose

The Teams

This first-of-its-kind treatment is the result of collaboration between UCSF, called the birthplace of fetal surgery, the Ottawa Hospital, and CHEO where Ayla was diagnosed and also treated. UCSF is conducting an ongoing clinical trial of the treatment.

The fourth collaborator is Duke University home of the world’s foremost experts on Pompe disease. Dr. Jennifer Cohen, Duke University assistant professor and co-lead study author, expressed her gratitude for the opportunity to offer the new treatment option to Ayla, thereby changing the course of this deadly disease.

UCSF has received approval from the FDA to treat eight lysosomal storage diseases. Enzyme replacement therapy in utero will be used in a Phase 1 clinical trial with ten participants. Pompe disease is one of the eight FDA-approved diseases.

The other diseases are mucopolysaccharidosis types I, II, IVa, VI, and VII. Also included are Gaucher disease types 2 and 3, and Wolman disease.

Two additional adult patients have been enrolled in the UCSF trial. Both patients are doing well and have completed a course of prenatal ERT.

In Conclusion

The in-utero treatment, the first of its kind, saved Ayla, who has not shown any signs of heart problems. Aula is a healthy toddler who has thus far met her developmental milestones while continuing to receive ERT.