[Novel therapies in neurometabolic diseases: the importance of early intervention]

Rev Neurol. 2017 May 17;64(s03):S25-S28.
[Article in Spanish]

Abstract

Introduction: Individually, neurometabolic diseases are ultra rare, but for some of them there is an effective treatment.

Development: Several recent therapeutic advances are reviewed. Today, the possibilities of treatment for lysosomal diseases have improved. In recent years the use of enzyme replacement therapy has become more widely extended to treat mucopolysaccharidosis type IVA (Morquio A), mucopolysaccharidosis type VII (Sly syndrome), lysosomal acid lipase deficiency and alpha-mannosidosis. It has been proven that very early treatment of mucopolysaccharidoses can change their natural course. Intrathecal enzyme replacement therapy is being tried in some mucopolysaccharidoses with cognitive involvement, in an attempt to halt neurodegeneration. Very positive results have been obtained with genetically modified autotransplants in late-onset infantile metachromatic leukodystrophy and research is being conducted on other pathologies (mucopolysaccharidosis type III, X-linked adrenoleukodystrophy). Novel outcomes are also being achieved in the treatment of some encephalopathies that are sensitive to vitamins or cofactors: triple therapy in pyridoxine dependency, treatment with thiamine for some subacute encephalopathies with involvement of the basal ganglia, treatment with folinic acid for children with cerebral folate deficiency, or treatment with cyclic pyranopterin monophosphate in molybdenum cofactor deficiency type A.

Conclusions: As neuropaediatricians we must update our knowledge, especially in the case of treatable neurometabolic pathologies, since early treatment can change their prognosis significantly.

Title: Terapias novedosas en enfermedades neurometabolicas: importancia de una intervencion precoz.

Introduccion. Las enfermedades neurometabolicas son individualmente ultrarraras, pero algunas de ellas tienen un tratamiento eficaz. Desarrollo. Se revisan algunas novedades terapeuticas. Las enfermedades lisosomales tienen actualmente mejores posibilidades de tratamiento. En los ultimos años se ha extendido el uso de la terapia enzimatica sustitutiva a la mucopolisacaridosis tipo IVA (Morquio A), a la mucopolisacaridosis tipo VII (enfermedad de Sly), al deficit de lipasa acida lisosomal y a la alfa-manosidosis. Se ha constatado que un tratamiento muy precoz de las mucopolisacaridosis puede cambiar su historia natural. Se esta probando la terapia enzimatica sustitutiva intratecal en algunas mucopolisacaridosis con afectacion cognitiva, en el intento de frenar la neurodegeneracion. Se han obtenido resultados muy positivos con autotrasplante modificado geneticamente en leucodistrofia metacromatica infantil tardia y se esta trabajando en otras patologias (mucopolisacaridosis tipo III, adrenoleucodistrofia ligada a X). Tambien hay novedades en la terapia de algunas encefalopatias sensibles a vitaminas o cofactores: la triple terapia en la dependencia de piridoxina, el tratamiento con tiamina de algunas encefalopatias subagudas con afectacion de ganglios basales, el tratamiento con acido folinico de niños con deficiencia de folato cerebral, o el tratamiento con monofosfato de piranopterina ciclico en los defectos de cofactor de molibdeno de tipo A. Conclusiones. Los neuropediatras debemos actualizar nuestro conocimiento especialmente en aquellas patologias neurometabolicas tratables, dado que una terapia precoz puede cambiar de forma significativa su pronostico.

Publication types

  • Review

MeSH terms

  • Avitaminosis / therapy
  • Brain Diseases, Metabolic, Inborn / diagnosis
  • Brain Diseases, Metabolic, Inborn / genetics
  • Brain Diseases, Metabolic, Inborn / therapy*
  • Carrier Proteins / metabolism
  • Child
  • Clinical Trials as Topic
  • Coenzymes / deficiency
  • Coenzymes / therapeutic use
  • Early Diagnosis
  • Early Medical Intervention*
  • Enzyme Replacement Therapy
  • Epilepsy / genetics
  • Epilepsy / metabolism
  • Epilepsy / therapy
  • Genetic Therapy
  • Humans
  • Infant, Newborn
  • Lysosomal Storage Diseases, Nervous System / drug therapy
  • Lysosomal Storage Diseases, Nervous System / genetics
  • Nervous System Diseases / diagnosis
  • Nervous System Diseases / therapy*
  • Therapies, Investigational*

Substances

  • Carrier Proteins
  • Coenzymes