Novel preclinical gene therapy approach for treating Niemann-Pick disease

Genzyme Corp. has announced the publication of a new study in The Proceedings of the National Academy of Sciences describing a novel preclinical gene therapy approach for treating Niemann-Pick disease.

The study, conducted by a team of Genzyme researchers, demonstrated that administering gene therapy both systemically and directly into the brain helped to preserve motor and cognitive functions and significantly extend lifespan in a mouse model of Niemann-Pick disease. The authors write that this combination approach may represent a promising clinical strategy for treating diseases that affect visceral organ systems as well as the central nervous system. Current treatments which do not cross the blood-brain barrier, such as enzyme replacement therapy, are limited in their effectiveness for such disorders with brain involvement.

In the study, Genzyme researchers tested the combination of brain and systemic injections of adeno-associated viral vectors encoding human acid sphingomyelinase, the enzyme that is deficient in patients with Niemann-Pick disease types A & B. This combination approach was compared to mice treated singly with either of the two modes of delivery, and to mice that were left untreated.

After 54 weeks of observation, the researchers found that combination therapy led to preservation of motor and cognitive functions at near normal levels. The combination-treated group also lived longer and was free of many of the neurological and physical manifestations of the disease shown in either of the singly treated groups or the non-treated group. Importantly, researchers established immune system tolerance to the therapy by administering it systemically before it was administered to the brain, which the paper suggests may be an important part of any strategy to apply these findings to a clinical setting.

The work published today builds on an extensive program at Genzyme to develop new and next-generation therapies for lysosomal storage disorders. Genzyme developed and now provides four enzyme replacement therapies for lysosomal storage disorders including Cerezyme(R) (imiglucerase for injection) for Gaucher disease, Fabrazyme(R) (agalsidase beta) for Fabry disease, Aldurazyme(R) (laronidase) for MPS I and Myozyme(R) (alglucosidase alfa) for Pompe disease. In addition, Genzyme is conducting a Phase 1 clinical trial of a potential enzyme replacement therapy for the treatment of ASM-deficient Niemann Pick disease. And the company recently completed enrollment in its ongoing Phase 2 clinical trial testing a novel oral therapy for Gaucher disease.

In addition to its preclinical work with lysosomal storage disorders, Genzyme's gene therapy portfolio includes two ongoing clinical trials, the most advanced of which is examining the safety and effectiveness of locally delivered Ad2/HIF-1 alpha, an engineered form of the HIF-1 alpha gene. This experimental therapy is designed to promote the growth of new blood vessels and improve circulation in the limbs of patients with peripheral arterial disease. Additionally, Genzyme is enrolling patients in a Phase 1-2 clinical trial of a gene therapy for Parkinson's disease designed to restore the therapeutic effectiveness of levo-Dopa, the primary treatment for Parkinson's disease, by enhancing the brain's ability to convert it into dopamine.

Genzyme is also conducting pre-clinical research using gene therapy in atrial fibrillation and macular degeneration through partnerships with Excigen, Inc., and Applied Genetic Technologies Corp., respectively.