The therapeutic use of gene therapy in inflammatory demyelinating diseases of the central nervous system.
OBJECTIVE
Gene therapy protocols aimed to deliver therapeutic molecules into the central nervous system may represent an alternative therapeutic strategy in patients affected by inflammatory demyelinating diseases of the central nervous system where systemic therapies have shown limited therapeutic efficacy possibly owing to the blood-brain barrier, a major obstacle for the entry of therapeutic molecules into the central nervous system.


RESULTS
Among inflammatory demyelinating diseases of the central nervous system, gene therapy approaches have been so far developed almost exclusively for multiple sclerosis. However, the chronic/relapsing nature of the disease, the restriction to the central nervous system of the pathological process as well as the necessity to inhibit the ongoing inflammatory process but also to foster endogenous remyelinating pathways, have posed several questions which still need to be properly addressed for the development of a successful gene therapy strategy in multiple sclerosis patients.


CONCLUSIONS
The gene therapy approaches for multiple sclerosis have been so far developed and tested only in rodents and monkeys with experimental autoimmune encephalomyelitis, the animal model of multiple sclerosis. The results of these studies clearly indicate that the delivery of therapeutic genes within the central nervous system is superior to the peripheral delivery. In particular, the intracerebral delivery of genes coding for anti-inflammatory and/or neurotrophic molecules, using gene vectors derived from non-replicative viruses, showed to inhibit not only the detrimental function of blood-borne mononuclear effector cells but also to foster proliferation and differentiation of surviving oligodendrocytes within demyelinated areas. Here, we summarize the most recent findings of this novel area of research.
Furlan
Roberto
R
Neuroimmunology Unit (DIBIT) and Department of Neurology and Neurophysiology, San Raffaele Scientific Institute, Milan, Italy.
Pluchino
Stefano
S
Martino
Gianvito
G
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002493:Central Nervous System Diseases / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D003711:Demyelinating Diseases / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000628:therapy; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007249:Inflammation; D009103:Multiple Sclerosis / Q000628:therapy; D009414:Nerve Growth Factors / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D009414:Nerve Growth Factors