Recombinant hexosaminidases conjugated to magnetite nanoparticles: Alternative therapeutic treatment routes in GM2 fibroblasts

Pulido, Zully; Cifuentes, Javier; Benincore, Eliana; Garzon, Rafael; Castellanos, María Claudia; Leal, Andrés Felipe; Cruz, Juan Carlos Hinojosa; Alméciga-Díaz, Carlos J.; Espejo-Mojica, Angela Johana

doi:10.1016/j.ymgme.2019.11.347

Cited by 3 publications

(2 citation statements)

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“…In vitro evaluation of recombinant HexA produced in P. pastoris showed normalized lipid accumulation in neural stem cells, showing the potential of this enzyme in the development of an ERT for GM2 gangliosidoses [ 104 ]. Recent efforts to allow the delivery of these recombinant Hex to CNS involved their conjugation with nanoparticles [ 105 ].…”

Section: Current Proposals For the Treatment Of Gm2 Gangliosidosesmentioning

confidence: 99%

GM2 Gangliosidoses: Clinical Features, Pathophysiological Aspects, and Current Therapies

Leal

Benincore-Flórez

Solano-Galarza

et al. 2020

IJMS

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GM2 gangliosidoses are a group of pathologies characterized by GM2 ganglioside accumulation into the lysosome due to mutations on the genes encoding for the β-hexosaminidases subunits or the GM2 activator protein. Three GM2 gangliosidoses have been described: Tay–Sachs disease, Sandhoff disease, and the AB variant. Central nervous system dysfunction is the main characteristic of GM2 gangliosidoses patients that include neurodevelopment alterations, neuroinflammation, and neuronal apoptosis. Currently, there is not approved therapy for GM2 gangliosidoses, but different therapeutic strategies have been studied including hematopoietic stem cell transplantation, enzyme replacement therapy, substrate reduction therapy, pharmacological chaperones, and gene therapy. The blood–brain barrier represents a challenge for the development of therapeutic agents for these disorders. In this sense, alternative routes of administration (e.g., intrathecal or intracerebroventricular) have been evaluated, as well as the design of fusion peptides that allow the protein transport from the brain capillaries to the central nervous system. In this review, we outline the current knowledge about clinical and physiopathological findings of GM2 gangliosidoses, as well as the ongoing proposals to overcome some limitations of the traditional alternatives by using novel strategies such as molecular Trojan horses or advanced tools of genome editing.

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Section: Current Proposals For the Treatment Of Gm2 Gangliosidosesmentioning

confidence: 99%

GM2 Gangliosidoses: Clinical Features, Pathophysiological Aspects, and Current Therapies

Leal

Benincore-Flórez

Solano-Galarza

et al. 2020

IJMS

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show abstract

“…Recombinant HexA produced in P. pastoris normalized lipid accumulation in neural stem cells derived from TSD iPSCs, showing the potential of this enzyme, and P. pastoris, in the development of an ERT for GM2 gangliosidosis [115]. Recent efforts to improve the delivery of this recombinant Hex to BBB, involved their conjugation with nanoparticles [116].…”

Section: Current Proposals For the Treatment Of Gm2 Gangliosidosismentioning

confidence: 99%

GM2 Gangliosidosis: Clinical Features and Current Therapies

Leal¹,

Benincore-Flórez²,

Solano-Galarza³

et al. 2020

Preprint

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GM2 gangliosidosis are a group of pathologies characterized by GM2 ganglioside accumulation into the lysosome due to mutations on the genes encoding for the β-hexosaminidases subunits or the GM2 activator protein. Three GM2 gangliosidosis have been described: Tay-Sachs disease, Sandhoff disease, and AB variant. Central nervous system dysfunction is the main characteristic of GM2 gangliosidosis patients that include neurodevelopment alterations, neuroinflammation, and neuronal apoptosis. Currently, there is not approved therapy for GM2 gangliosidosis, but different therapeutic strategies have been studied including hematopoietic stem cell transplantation, enzyme replacement therapy, substrate reduction therapy, pharmacological chaperones, and gene therapy. The blood-brain barrier represents a challenge for the development of therapeutic agents for these disorders. In this sense, alternative routes of administration (e.g. intrathecal or intracerebroventricular) have been evaluated, as well as the design of fusion peptides that allow the protein transport from the brain capillaries to the central nervous system. In this review, we outline the current knowledge about clinical and physiopathological findings of GM2 gangliosidosis, as well as the ongoing proposals to overcome some limitations of the traditional alternatives by using novel strategies such as molecular Trojan horses or advanced tools of genome editing.

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GM2-gangliosidosis, type I (Tay – Sachs disease) in the pediatrician practice

et al. 2021

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Background. GM2-gangliosidosis, type I (Tay-Sachs disease) is rare hereditary disease caused by mutations in the HEXA gene encoding the alpha subunit of lysosomal hexosaminidase A. It leads to accumulation of GM2-ganglioside in lysosomes and cell death. The major clinical signs of this disease are regression of motor and psychoverbal skills, progressive macrocephaly, diffuse muscle hypotension, convulsive disorder. Almost all patients with this disease have the “cherry red spot” symptom on the fundus of the eye.Clinical case description. We show clinical description of the patient with disease manifested with the lesion of visual analyzer. The child was sent for geneticist’s consultation due to revealed ophthalmic picture of the “cherry red spot” symptom on the fundus of the eye. Molecular genetic testing has revealed in the patient c.1274_1278 dupTATC (CI 880091) mutation in homozygous state in HEXA gene.Concllusion. Differential diagnosis of this disease should be performed with other diseases from the group of inherited metabolic diseases associated with early regression of psychomotor skills, progressive vision loss, “cherry red spot” symptom on the fundus of the eye and convulsive disorder

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Recombinant hexosaminidases conjugated to magnetite nanoparticles: Alternative therapeutic treatment routes in GM2 fibroblasts

Cited by 3 publications

References 0 publications

GM2 Gangliosidoses: Clinical Features, Pathophysiological Aspects, and Current Therapies

GM2 Gangliosidoses: Clinical Features, Pathophysiological Aspects, and Current Therapies

GM2 Gangliosidosis: Clinical Features and Current Therapies

GM2-gangliosidosis, type I (Tay – Sachs disease) in the pediatrician practice

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