Lysosomial Storage Disorders (LSDs) are genetic diseases due to a lysosomial dysfunction [1]. LSDs are generally caused
by mutations on gene transcribing for a crucial enzyme involved in a metabolic or catabolic biochemical step of a metabolic
pathway driving to the accumulation of the not cabolized enzymatic target within the lysosome. Owing to this progressive intralysosomial
accumulation lysosomial diseases are characterized by several organ symptoms involving specific or multiple organs
[2]. Since this pathogenetic basis of LSDs, they are potential target for gene therapy in order to obtain the single gene induction
into some target cells aiming to improve the clinical course of progressive end-organ damage due to continous substrate
accumulation [3].
Other possible therapeutic approaches have been reported such as Bone Marrow Transplantation (BMT) or Enzyme Replacement
Therapy (ERT) and these therapeutic ways have been reported as able to modify with a various degree the he systemic
disease associated with LSDs in some patients.
Nevertheless, Central Nervous System (CNS) involvement still appear as a maior therapeutic a major challenge. With regard
of treatment of neurologic complications of LSDs cene therapy could be evaluated as a promising future approach for the
treatment of CNS disease in order to provide a effective and persistent improvement of the deficient enzyme [4].
Direct intracranial injection of viral gene transfer vectors represents a possible effective therapeutical approach on the basis
of promising results reported in some animal models of LSDs such as canine and feline models of lysosomial accumulation
diseases.
Aim of this mini-thematic issue is to review the state of art of gene therapy in LSDs In the first review, Simonetta et al. [5]
reviewed genetics and the role of genetic therapy in Anderson-fabry Disease (AFD). Because of its multisystemic involvement,
Fabry’s disease may present a large spectrum of clinical manifestations as acroparesthesias, hypohidrosis, angiokeratomas,
signs and symptoms of cardiac, renal, cerebrovascular involvement (renal insufficiency, proteinuria, left ventricular hypertrophy,
strokes) [5-10].
Enzyme replacement therapy with recombinant α-galactosidase A is actually the specific therapy for Fabry’s disease but recently
viral gene therapy has recently been addressed with great interest or the last innovative method, that is to say, for delivering
recombination enzyme into the main involved tissues and promising results have been reported in animal models.
In the second review, Sestito et al. [11] reviewed the role of genetics and genetic therapy in Hunter syndrome. Hunter syndrome
is a rare X-linked lysosomal storage disorder due to a mutation in the gene encoding the lysosomal enzyme iduronate-2-
sulfatase. The Author reported that In vitro studies firstly aimed at the demonstration that viral vector-mediated IDS gene expression
could lead to high levels of enzyme activity in trasduced cells, whereas in vivo studies in which recombinant vectors
are directly administered, systematically or by direct injection into the Central Nervous System, also ex vivo gene therapy, consisting
of the transplantation of autologous hematopoietic stem cells, modified in vitro, into the animal or patient, indicate future
promising results.
In the third review, Cachón-González et al., [12] reviewed genetics and gene therapy in GM2 Gangliosidosis. There is no
effective treatment beyond palliative care, and while the genetic basis of GM2 gangliosidosis is well established, the molecular
and cellular events, from disease-causing mutations and glycosphingolipid storage to disease manifestations, remain to be fully
delineated. Several therapeutic approaches have been attempted in patients, including enzymatic augmentation, bone marrow
transplantation, enzyme enhancement, and substrate reduction therapy. Animal models of GM2 gangliodidosis have facilitated in-depth evaluation of innovative applications such as gene transfer, which in contrast to other interventions, show great promise.
