Sphingomyelinase Deficiency Medication

Updated: May 29, 2020
  • Author: Jaimin M Patel, MD, MBBS, MS; Chief Editor: Luis O Rohena, MD, MS, FAAP, FACMG  more...
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Medication Summary

Currently, there are no targeted therapies available for Niemann-Pick disease (NPD) type A. Gene therapies, enzyme replacement therapies, and bone marrow transplantations have been studied in animal models, but the challenge is to deliver treatments directly into the central nervous system (CNS) before the onset of neurologic symptoms. Safety assessment of intracranial injection of biologic vectors into the brain is still under discussion. [2]

For NPD type B, recombinant human ASM (rhASM) treatment for non-neurologic manifestations is undergoing clinical trial. [21, 22, 23]  Recombinant human ASM has been successfully produced in Chinese hamster ovary cells. Initial treatment studies were conducted in animal models, specifically, in ASM knockout mice. Treatment with rhASM in these animals resulted in dose-dependent toxicity. Such toxicity could be prevented by dose escalation to debulk stored sphingomyelin and thus maintain a low level of ceramide release.

Subsequent studies have begun in humans. In a phase 1 study in adult patients, single administrations of rhASM (olipudase alfa) in increasing doses once every 2 weeks were undertaken, without adverse events. A 0.6 mg/kg maximum starting dose was determined. Transient elevation of cytokines and bilirubin was observed in this cohort. [22] In Phase 1b, a dose escalation scheme was used in five adult patients, first with low doses to debulk sphingomyelin in tissues, then with dose escalations of up to 3 mg/kg, for a total of 26 weeks. No serious adverse events were encountered. [21] A randomized phase 2/3 trial is underway.

Miglustat is first and only targeted therapy approved for NPD type C. [24]