Highlights
- •There is an immense challenge to develop novel therapies for neurometabolic epilepsies.
- •There have been recent dramatic developments in our understanding of the pathomechanisms of neurometabolic epilepsies.
- •This review outlines the emergent targeted established or investigated therapeutics for neurometabolic epilepsies.
- •Multicenter collaborations should be implemented to advance our knowledge of these unique diseases.
Abstract
The rarity and heterogeneity of neurometabolic diseases make it challenging to reach
evidence-based principles for their specific treatments. Indeed, current treatments
for many of these diseases remain symptomatic and supportive. However, an ongoing
scientific and medical revolution has led to dramatic breakthroughs in molecular sciences
and genetics, revealing precise pathophysiologic mechanisms. Accordingly, this has
led to significant progress in the development of novel therapeutic approaches aimed
at treating epilepsy resulting from these conditions, as well as their other manifestations.
We overview recent notable treatment advancements, from vitamins, trace minerals,
and diets to unique medications targeting the elemental pathophysiology at a molecular
or cellular level, including enzyme replacement therapy, enzyme enhancing therapy,
antisense oligonucleotide therapy, stem cell transplantation, and gene therapy.
Keywords
Abbreviations:
AADC (Aromatic L-amino acid decarboxylase), AAV (Adenovirus-associated vector), AMO (Antisense morpholino oligonucleotides), ARG1 (Recombinant arginase 1), ASL (Arginosuccinate lyase), ASS1 (Arginosuccinate synthetase-1), BBB (Blood-brain-barrier), BCAA (Branched-chain-amino-acids), CGDs (Congenital disorders of glycosylation), CLN2 (Ceroid lipofuscinosis or), CNS (Central nervous system), CPT1 (Carnitine palmitoyltransferase I), CPT2 (Carnitine palmitoyltransferase type 2), DEND (Developmental delay-epilepsy-neonatal diabetes), EET (Enzyme enhancement therapy), ERT (Enzyme replacement therapy), FAO (Fatty acid oxidation), FDA (Food and Drug Administration), GABA (γ-aminobutyric acid), GDH (Glutamate dehydrogenase), Glut-1 (Glucose transporter type I), GSDs (Glycogen storage diseases), HIHA (Hyperinsulinism hyperammonemia), IVA (Isovaleric acidemia), IVIG (intravenous immune globulin), LCHAD (Long-chain 3-hydroxy acyl-CoA dehydrogenase), LND (Lesch–Nyhan disease), LNP (Lipid nanoparticles), LSDs (Lysosomal storage diseases), MCAD (Multiple acyl-CoA dehydrogenase), MCT (Medium-chain triglyceride), MDs (Mitochondrial Diseases), mtDNA (Mitochondrial deoxyribonucleic acid), MMA (Methylmalonic acidemia), MPS (Mucopolysaccharidoses), MSUD (Maple syrup urine disease), OTC (Ornithine Transcarbamylase), PA (Propionic acidemia), PKU (Phenylketonuria), PLP (Pyridoxal-5-phosphate), PNPO (Pyridoxamine-5′-phosphate oxidase), PPAR (proliferator-activated receptor), SSADH (Succinic semialdehyde dehydrogenase), TPP1 (Tripeptidyl peptidase 1), UCDs (Urea cycle disorders), VLCAD (Very-long-chain acyl-CoA dehydrogenase), XLALD (X-linked adrenoleukodystrophy)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: March 29, 2023
Accepted:
March 12,
2023
Received in revised form:
March 11,
2023
Received:
August 15,
2022
Identification
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