The treatment of juvenile/adult GM1-gangliosidosis with Miglustat may reverse disease progression

Federica Deodato, Elena Procopio, Angelica Rampazzo, Roberta Taurisano, Maria Alice Donati, Carlo Dionisi-Vici, Anna Caciotti, Amelia Morrone, Maurizio Scarpa

Research output: Contribution to journalArticle

Abstract

Juvenile and adult GM1-gangliosidosis are invariably characterized by progressive neurological deterioration. To date only symptomatic therapies are available. We report for the first time the positive results of Miglustat (OGT 918, N-butyl-deoxynojirimycin) treatment on three Italian GM1-gangliosidosis patients. The first two patients had a juvenile form (enzyme activity ≤5%, GLB1 genotype p.R201H/c.1068 + 1G > T; p.R201H/p.I51N), while the third patient had an adult form (enzyme activity about 7%, p.T329A/p.R442Q). Treatment with Miglustat at the dose of 600 mg/day was started at the age of 10, 17 and 28 years; age at last evaluation was 21, 20 and 38 respectively. Response to treatment was evaluated using neurological examinations in all three patients every 4–6 months, the assessment of Movement Disorder-Childhood Rating Scale (MD-CRS) in the second patient, and the 6-Minute Walking Test (6-MWT) in the third patient. The baseline neurological status was severely impaired, with loss of autonomous ambulation and speech in the first two patients, and gait and language difficulties in the third patient. All three patients showed gradual improvement while being treated; both juvenile patients regained the ability to walk without assistance for few meters, and increased alertness and vocalization. The MD-CRS class score in the second patient decreased from 4 to 2. The third patient improved in movement and speech control, the distance covered during the 6-MWT increased from 338 to 475 m. These results suggest that Miglustat may help slow down or reverse the disease progression in juvenile/adult GM1-gangliosidosis.

Original languageEnglish
Pages (from-to)1529-1536
Number of pages8
JournalMetabolic Brain Disease
Volume32
Issue number5
DOIs
Publication statusPublished - Oct 1 2017

Fingerprint

GM1 Gangliosidosis
Disease Progression
Enzyme activity
Therapeutics
Walking
Deterioration
Movement Disorders
miglustat
Aptitude
Neurologic Examination
Enzymes
Gait

Keywords

  • GM1-gangliosidosis
  • Miglustat
  • NB-DNJ
  • Substrate reduction therapy

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

The treatment of juvenile/adult GM1-gangliosidosis with Miglustat may reverse disease progression. / Deodato, Federica; Procopio, Elena; Rampazzo, Angelica; Taurisano, Roberta; Donati, Maria Alice; Dionisi-Vici, Carlo; Caciotti, Anna; Morrone, Amelia; Scarpa, Maurizio.

In: Metabolic Brain Disease, Vol. 32, No. 5, 01.10.2017, p. 1529-1536.

Research output: Contribution to journalArticle

Deodato, Federica ; Procopio, Elena ; Rampazzo, Angelica ; Taurisano, Roberta ; Donati, Maria Alice ; Dionisi-Vici, Carlo ; Caciotti, Anna ; Morrone, Amelia ; Scarpa, Maurizio. / The treatment of juvenile/adult GM1-gangliosidosis with Miglustat may reverse disease progression. In: Metabolic Brain Disease. 2017 ; Vol. 32, No. 5. pp. 1529-1536.
@article{a3126c5153a843c2ad7d29bf0aca69e2,
title = "The treatment of juvenile/adult GM1-gangliosidosis with Miglustat may reverse disease progression",
abstract = "Juvenile and adult GM1-gangliosidosis are invariably characterized by progressive neurological deterioration. To date only symptomatic therapies are available. We report for the first time the positive results of Miglustat (OGT 918, N-butyl-deoxynojirimycin) treatment on three Italian GM1-gangliosidosis patients. The first two patients had a juvenile form (enzyme activity ≤5{\%}, GLB1 genotype p.R201H/c.1068 + 1G > T; p.R201H/p.I51N), while the third patient had an adult form (enzyme activity about 7{\%}, p.T329A/p.R442Q). Treatment with Miglustat at the dose of 600 mg/day was started at the age of 10, 17 and 28 years; age at last evaluation was 21, 20 and 38 respectively. Response to treatment was evaluated using neurological examinations in all three patients every 4–6 months, the assessment of Movement Disorder-Childhood Rating Scale (MD-CRS) in the second patient, and the 6-Minute Walking Test (6-MWT) in the third patient. The baseline neurological status was severely impaired, with loss of autonomous ambulation and speech in the first two patients, and gait and language difficulties in the third patient. All three patients showed gradual improvement while being treated; both juvenile patients regained the ability to walk without assistance for few meters, and increased alertness and vocalization. The MD-CRS class score in the second patient decreased from 4 to 2. The third patient improved in movement and speech control, the distance covered during the 6-MWT increased from 338 to 475 m. These results suggest that Miglustat may help slow down or reverse the disease progression in juvenile/adult GM1-gangliosidosis.",
keywords = "GM1-gangliosidosis, Miglustat, NB-DNJ, Substrate reduction therapy",
author = "Federica Deodato and Elena Procopio and Angelica Rampazzo and Roberta Taurisano and Donati, {Maria Alice} and Carlo Dionisi-Vici and Anna Caciotti and Amelia Morrone and Maurizio Scarpa",
year = "2017",
month = "10",
day = "1",
doi = "10.1007/s11011-017-0044-y",
language = "English",
volume = "32",
pages = "1529--1536",
journal = "Metabolic Brain Disease",
issn = "0885-7490",
publisher = "Springer New York",
number = "5",

}

TY - JOUR

T1 - The treatment of juvenile/adult GM1-gangliosidosis with Miglustat may reverse disease progression

AU - Deodato, Federica

AU - Procopio, Elena

AU - Rampazzo, Angelica

AU - Taurisano, Roberta

AU - Donati, Maria Alice

AU - Dionisi-Vici, Carlo

AU - Caciotti, Anna

AU - Morrone, Amelia

AU - Scarpa, Maurizio

PY - 2017/10/1

Y1 - 2017/10/1

N2 - Juvenile and adult GM1-gangliosidosis are invariably characterized by progressive neurological deterioration. To date only symptomatic therapies are available. We report for the first time the positive results of Miglustat (OGT 918, N-butyl-deoxynojirimycin) treatment on three Italian GM1-gangliosidosis patients. The first two patients had a juvenile form (enzyme activity ≤5%, GLB1 genotype p.R201H/c.1068 + 1G > T; p.R201H/p.I51N), while the third patient had an adult form (enzyme activity about 7%, p.T329A/p.R442Q). Treatment with Miglustat at the dose of 600 mg/day was started at the age of 10, 17 and 28 years; age at last evaluation was 21, 20 and 38 respectively. Response to treatment was evaluated using neurological examinations in all three patients every 4–6 months, the assessment of Movement Disorder-Childhood Rating Scale (MD-CRS) in the second patient, and the 6-Minute Walking Test (6-MWT) in the third patient. The baseline neurological status was severely impaired, with loss of autonomous ambulation and speech in the first two patients, and gait and language difficulties in the third patient. All three patients showed gradual improvement while being treated; both juvenile patients regained the ability to walk without assistance for few meters, and increased alertness and vocalization. The MD-CRS class score in the second patient decreased from 4 to 2. The third patient improved in movement and speech control, the distance covered during the 6-MWT increased from 338 to 475 m. These results suggest that Miglustat may help slow down or reverse the disease progression in juvenile/adult GM1-gangliosidosis.

AB - Juvenile and adult GM1-gangliosidosis are invariably characterized by progressive neurological deterioration. To date only symptomatic therapies are available. We report for the first time the positive results of Miglustat (OGT 918, N-butyl-deoxynojirimycin) treatment on three Italian GM1-gangliosidosis patients. The first two patients had a juvenile form (enzyme activity ≤5%, GLB1 genotype p.R201H/c.1068 + 1G > T; p.R201H/p.I51N), while the third patient had an adult form (enzyme activity about 7%, p.T329A/p.R442Q). Treatment with Miglustat at the dose of 600 mg/day was started at the age of 10, 17 and 28 years; age at last evaluation was 21, 20 and 38 respectively. Response to treatment was evaluated using neurological examinations in all three patients every 4–6 months, the assessment of Movement Disorder-Childhood Rating Scale (MD-CRS) in the second patient, and the 6-Minute Walking Test (6-MWT) in the third patient. The baseline neurological status was severely impaired, with loss of autonomous ambulation and speech in the first two patients, and gait and language difficulties in the third patient. All three patients showed gradual improvement while being treated; both juvenile patients regained the ability to walk without assistance for few meters, and increased alertness and vocalization. The MD-CRS class score in the second patient decreased from 4 to 2. The third patient improved in movement and speech control, the distance covered during the 6-MWT increased from 338 to 475 m. These results suggest that Miglustat may help slow down or reverse the disease progression in juvenile/adult GM1-gangliosidosis.

KW - GM1-gangliosidosis

KW - Miglustat

KW - NB-DNJ

KW - Substrate reduction therapy

UR - http://www.scopus.com/inward/record.url?scp=85020083353&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85020083353&partnerID=8YFLogxK

U2 - 10.1007/s11011-017-0044-y

DO - 10.1007/s11011-017-0044-y

M3 - Article

AN - SCOPUS:85020083353

VL - 32

SP - 1529

EP - 1536

JO - Metabolic Brain Disease

JF - Metabolic Brain Disease

SN - 0885-7490

IS - 5

ER -