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.