Intracerebroventricular Enzyme Replacement Therapy Offers New Hope for Sanfilippo Syndrome Type B
Sanfilippo syndrome type B (MPS IIIB) is a rare, genetic, neurodegenerative disease.
Due to a missing enzyme, children with Sanfilippo syndrome type B experience a build-up of heparan sulfate, which in turn damages cells of the central nervous system and other organs in the body. Speech/developmental delays, behavioral symptoms, sleep disturbances and hearing impairments are common and are followed by progressive intellectual disability, seizures and loss of mobility in later stages of the disease. Children with Sanfilippo syndrome type B often pass away in their late teens or early twenties. There are no approved treatments for this devastating disorder.
We are developing tralesinidase alfa
(AX 250), an enzyme replacement therapy, to treat Sanfilippo syndrome type B.
Tralesinidase alfa is delivered through intracerebroventricular (ICV) administration, where the drug is injected into an Ommaya reservoir—a small, plastic device implanted by doctors under a child’s scalp—to bypass the blood-brain barrier and send medication into the cerebrospinal fluid that bathes cells of the central nervous system. This technique has been used for six decades to treat other diseases, including brain tumors, leukemia and, most recently, another form of childhood dementia (CLN2 disease). ICV administration delivers tralesinidase alfa to the brain and throughout the body, potentially treating all aspects of Sanfilippo syndrome type B disease.
Five-Part Reservoir Placement Process
Shave a small area near the implant site
Make a small incision in the skin and drill a small hole through the skull
Position the reservoir within the incision
Thread a catheter connected to the reservoir into one of the fluid-filled spaces inside the brain
Close the incision with sutures
Less than 1 hour
The reservoir appears as a small bump underneath the patient’s regrown hair, similar in size to the tip of a pinky finger
During weekly appointments, doctors insert a needle through the reservoir to deliver medication to the brain
Our Ongoing Clinical Development Program
The ultimate goals of an effective Sanfilippo syndrome type B treatment are to normalize heparan sulfate levels and clear accumulated heparan sulfate from the body.
As in other mucopolysaccharidoses for which treatments are already available, clearance of heparan sulfate is expected to prevent further tissue damage and hopefully reverse some of the damage that has already occurred. This should in turn lead to clinical benefits in the form of preservation of current skills, symptomatic relief, and a higher quality of life for Sanfilippo syndrome type B patients.
Effective therapies for Sanfilippo syndrome type B need to accomplish 4 goals
The therapy must normalize heparan sulfate levels in tissues and body fluids (CSF and plasma)
Clearance of heparan sulfate should lead to normalization of affected organ size
Functional and structural improvements in affected organs should follow
Following the first 3 steps, clinical benefits should include stabilization and/or improvement of clinical symptoms, leading to a higher quality of life for Sanfilippo syndrome type B patients
We’re conducting large, comprehensive Sanfilippo syndrome type B natural history and treatment studies to understand disease progression and tralesinidase alfa’s potential as a safe and effective therapy.
Our data to date show that tralesinidase alfa normalizes heparan sulfate levels and liver size in treated Sanfilippo syndrome type B patients, suggesting its effectiveness at clearing heparan sulfate.
We are currently studying how normalization of heparan sulfate levels affects cognition, communication, behavior, sleep, and quality of life of our treated patients. In addition, the safety profile of tralesinidase alfa is consistent with that seen with other enzyme replacement therapies and other types of therapies delivered via intracerebroventricular administration.
These results suggest that tralesinidase alfa holds promise to become a first- and best-in-class treatment for Sanfilippo syndrome type B.