Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-8448b6f56d-wq2xx Total loading time: 0 Render date: 2024-04-25T00:16:55.769Z Has data issue: false hasContentIssue false

Chapter 32 - Novel Therapeutic Approaches to Metabolic Movement Disorders

from Section III - Conclusions and Future Directions

Published online by Cambridge University Press:  24 September 2020

By
Gabriella A. Horvath  and
Clara D. van Karnebeek
Edited by
Darius Ebrahimi-Fakhari  and
Phillip L. Pearl
Darius Ebrahimi-Fakhari
Affiliation:
Harvard Medical School
Phillip L. Pearl
Affiliation:
Harvard Medical School
Get access

Summary

Movement disorders are common symptoms in patients with inborn errors of metabolism (IEMs), and have a serious impact on their quality of life. Treatment of the movement disorder is usually causal, i.e. aimed at the underlying condition. More and more therapeutic strategies are emerging for many IEMs, varying from dietary restriction/supplementation, enzyme cofactor/vitamin supplementation, enzyme-replacement, substrate inhibition, substrate reduction, bone marrow or hematopoietic stem-cell transplantation (HSCT), gene therapy, or newer symptomatic treatment modalities. Dietary manipulations typically aim at substrate reduction, i.e. decreasing the intake of toxic precursors or providing the deficient product. Vitamins and cofactors are used because in some disorders the synthesis of these is affected, while in others these catalyze residual enzyme activity and stability, or act as chaperones.

Type
Chapter
Information
Movement Disorders and Inherited Metabolic Disorders
Recognition, Understanding, Improving Outcomes
 , pp. 393 - 410
Publisher: Cambridge University Press
Print publication year: 2020

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Ginocchio, VM, Brunetti-Pierri, N. Progress toward improved therapies for inborn errors of metabolism. Hum Mol Genet. 2016;25(R1):R27–35.CrossRefGoogle ScholarPubMed
Piguet, F, Alves, S, Cartier, N. Clinical gene therapy for neurodegenerative diseases: Past, present, and future. Hum Gene Ther. 2017;28(11):988–1003.CrossRefGoogle ScholarPubMed
Geraets, RD, Koh, S, Hastings, ML, et al. Moving towards effective therapeutic strategies for neuronal ceroid lipofuscinosis. Orphanet J Rare Dis. 2016;11:40.Google Scholar
Pastores, GM. Therapeutic approaches for lysosomal storage diseases. Ther Adv Endocrinol Metab. 2010;1(4):177–88.CrossRefGoogle ScholarPubMed
Sanchez-Fernandez, EM, Garcia Fernandez, JM, Mellet, CO. Glycomimetic-based pharmacological chaperones for lysosomal storage disorders: Lessons from Gaucher, GM1-gangliosidosis and Fabry diseases. Chem Commun (Camb). 2016;52(32):5497–515.CrossRefGoogle ScholarPubMed
van den Broek, BTA, Page, K, Paviglianiti, A, et al. Early and late outcomes after cord blood transplantation for pediatric patients with inherited leukodystrophies. Blood Adv. 2018;2(1):49–60.CrossRefGoogle ScholarPubMed
Chandler, RJ, Venditti, CP. Gene therapy for metabolic diseases. Transl Sci Rare Dis. 2016;1(1):73–89.Google Scholar
Schneller, JL, Lee, CM, Bao, G, Venditti, CP. Genome editing for inborn errors of metabolism: Advancing towards the clinic. BMC Med. 2017;15(1):43.Google Scholar
Enns, GM, Cohen, BH. Clinical trials in mitochondrial disease: An update on EPI-743 and RP103. J Inborn Error Metab Screen. 2017;5:2326409817733013.Google Scholar
Viscomi, C. Toward a therapy for mitochondrial disease. Biochem Soc Trans. 2016;44(5):1483–90.Google Scholar
Nightingale, H, Pfeffer, G, Bargiela, D, Horvath, R, Chinnery, PF. Emerging therapies for mitochondrial disorders. Brain. 2016;139(Pt 6):1633–48.CrossRefGoogle ScholarPubMed
Yoon, DH, Kwon, OY, Mang, JY, et al. Protective potential of resveratrol against oxidative stress and apoptosis in Batten disease lymphoblast cells. Biochem Biophys Res Commun. 2011;414(1):49–52.Google Scholar
Wei, H, Kim, SJ, Zhang, Z, et al. ER and oxidative stresses are common mediators of apoptosis in both neurodegenerative and non-neurodegenerative lysosomal storage disorders and are alleviated by chemical chaperones. Hum Mol Genet. 2008;17(4):469-77.CrossRefGoogle ScholarPubMed
Johnson, SC, Yanos, ME, Kayser, EB, et al. mTOR inhibition alleviates mitochondrial disease in a mouse model of Leigh syndrome. Science. 2013;342(6165):1524–8.Google Scholar
Nagamani, SC, Campeau, PM, Shchelochkov, OA, et al. Nitric-oxide supplementation for treatment of long-term complications in argininosuccinic aciduria. Am J Hum Genet. 2012;90(5):836–46.Google Scholar
Brunetti-Pierri, N, Erez, A, Shchelochkov, O, Craigen, W, Lee, B. Systemic hypertension in two patients with ASL deficiency: A result of nitric oxide deficiency? Mol Genet Metab. 2009; 98 (1–2): 195–7.CrossRefGoogle ScholarPubMed
Alkufri, F, Harrower, T, Rahman, Y, et al. Molybdenum cofactor deficiency presenting with a parkinsonism–dystonia syndrome. Mov Disord. 2013;28(3):399–401.CrossRefGoogle ScholarPubMed
Carman, KB, Yildirim, GK, Kiral, E, et al. Status dystonicus: A rare presentation of molybdenum cofactor deficiency. Int J Clin Pediatr. 2017; 6 (3-4): 51–3.CrossRefGoogle Scholar
Lee, HJ, Adham, IM, Schwarz, G, et al. Molybdenum cofactor-deficient mice resemble the phenotype of human patients. Hum Mol Genet. 2002;11(26):3309–17.CrossRefGoogle ScholarPubMed
Schwarz, G, Santamaria-Araujo, JA, Wolf, S, et al. Rescue of lethal molybdenum cofactor deficiency by a biosynthetic precursor from Escherichia coli. Hum Mol Genet. 2004;13(12):1249–55.CrossRefGoogle ScholarPubMed
Veldman, A, Santamaria-Araujo, JA, Sollazzo, S, et al. Successful treatment of molybdenum cofactor deficiency type A with cPMP. Pediatrics. 2010;125(5):e1249–54.Google Scholar
Hitzert, MM, Bos, AF, Bergman, KA, et al. Favorable outcome in a newborn with molybdenum cofactor type A deficiency treated with cPMP. Pediatrics. 2012;130(4):e1005–10.Google Scholar
Schwahn, BC, Van Spronsen, FJ, Belaidi, AA, et al. Efficacy and safety of cyclic pyranopterin monophosphate substitution in severe molybdenum cofactor deficiency type A: A prospective cohort study. Lancet. 2015;386(10007):1955–63.CrossRefGoogle ScholarPubMed
Zorzi, G, Zibordi, F, Chiapparini, L, et al. Iron-related MRI images in patients with pantothenate kinase-associated neurodegeneration (PKAN) treated with deferiprone: Results of a phase II pilot trial. Mov Disord. 2011;26(9):1756–9.CrossRefGoogle ScholarPubMed
Hayflick, SJ, Hogarth, P. As iron goes, so goes disease? Haematologica. 2011;96(11):1571–2.Google Scholar
Schneider, SA, Dusek, P, Hardy, J, et al. Genetics and pathophysiology of neurodegeneration with brain iron accumulation (NBIA). Curr Neuropharmacol. 2013;11(1):59–79.Google ScholarPubMed
Hogarth, P. Neurodegeneration with brain iron accumulation: Diagnosis and management. J Mov Disord. 2015;8(1):1–13.Google Scholar
Rana, A, Seinen, E, Siudeja, K, et al. Pantethine rescues a Drosophila model for pantothenate kinase-associated neurodegeneration. Proc Natl Acad Sci USA. 2010;107(15):6988–93.Google Scholar
Brunetti, D, Dusi, S, Giordano, C, et al. Pantethine treatment is effective in recovering the disease phenotype induced by ketogenic diet in a pantothenate kinase-associated neurodegeneration mouse model. Brain. 2014;137(Pt 1):57–68.Google Scholar
TIRCON (Treat Iron-Related Childhood-Onset Neurodegeneration). Report summary: Project ID 277984, funded by FP7-HEALTH. June 5, 2017. Available from: https://cordis.europa.eu/project/id/277984/reporting/de.Google Scholar
Elbaum, D, Beconi, MG, Monteagudo, E, et al. Fosmetpantotenate (RE-024), a phosphopantothenate replacement therapy for pantothenate kinase-associated neurodegeneration: Mechanism of action and efficacy in nonclinical models. PLoS One. 2018;13(3):e0192028.CrossRefGoogle ScholarPubMed
Mazzocchi-Jones, D. Impaired corticostriatal LTP and depotentiation following iPLA2 inhibition is restored following acute application of DHA. Brain Res Bull. 2015;111:69–75.CrossRefGoogle ScholarPubMed
Schneider, SA, Kurian, MA. What the future holds for the genetic diagnosis for neurodegeneration with brain iron accumulation syndromes? Expert Opinion on Orphan Drugs. 2015;3(4):353–6.CrossRefGoogle Scholar
Hogarth, P, Kurian, MA, Gregory, A, et al. Consensus clinical management guideline for pantothenate kinase-associated neurodegeneration (PKAN). Mol Genet Metab. 2017;120(3):278–87.Google Scholar
Pascual, JM, Liu, P, Mao, D, et al. Triheptanoin for glucose transporter type I deficiency (G1D): Modulation of human ictogenesis, cerebral metabolic rate, and cognitive indices by a food supplement. JAMA Neurol. 2014;71(10):1255–65.Google Scholar
Mochel, F, Hainque, E, Gras, D, et al. Triheptanoin dramatically reduces paroxysmal motor disorder in patients with GLUT1 deficiency. J Neurol Neurosurg Psychiatry. 2016;87(5):550–3.Google Scholar
Schols, L, Rattay, TW, Martus, P, et al. Hereditary spastic paraplegia type 5: Natural history, biomarkers and a randomized controlled trial. Brain. 2017;140(12):3112–27.CrossRefGoogle ScholarPubMed
Mignarri, A, Malandrini, A, Del Puppo, M, et al. Treatment of SPG5 with cholesterol-lowering drugs. J Neurol. 2015;262(12):2783–5.Google Scholar
Scholl-Burgi, S, Holler, A, Pichler, K, et al. Ketogenic diets in patients with inherited metabolic disorders. J Inherit Metab Dis. 2015;38(4):765–73.Google Scholar
Pearl, PL, Schreiber, J, Theodore, WH, et al. Taurine trial in succinic semialdehyde dehydrogenase deficiency and elevated CNS GABA. Neurology. 2014;82(11):940–4.Google Scholar
Mohamed, FE, Al-Gazali, L, Al-Jasmi, F, Ali, BR. Pharmaceutical chaperones and proteostasis regulators in the therapy of lysosomal storage disorders: Current perspective and future promises. Front Pharmacol. 2017;8:448.Google Scholar
Balch, WE, Morimoto, RI, Dillin, A, Kelly, JW. Adapting proteostasis for disease intervention. Science. 2008;319(5865):916–9.Google Scholar
Singh, LR, Gupta, S, Honig, NH, Kraus, JP, Kruger, WD. Activation of mutant enzyme function in vivo by proteasome inhibitors and treatments that induce Hsp70. PLoS Genet. 2010;6(1):e1000807.Google Scholar
Narita, A, Shirai, K, Itamura, S, et al. Ambroxol chaperone therapy for neuronopathic Gaucher disease: A pilot study. Ann Clin Transl Neurol. 2016;3(3):200–15.Google Scholar
Motabar, O, Huang, W, Marugan, JJ, et al. Identification of modulators of the n370s mutant form of glucocerebrosidase as a potential therapy for gaucher disease: Chemotype 1. 2010;Mar 24 (updated May 5, 2011). In Probe Reports from the NIH Molecular Libraries Program. Bethesda, MD: National Center for Biotechnology Information (US). Available from: www-ncbi-nlm-nih-gov.ezp-prod1.hul.harvard.edu/books/NBK63601/.Google Scholar
Goldin, E, Zheng, W, Motabar, O, et al. High throughput screening for small molecule therapy for Gaucher disease using patient tissue as the source of mutant glucocerebrosidase. PLoS One. 2012;7(1):e29861.Google Scholar
Steet, RA, Chung, S, Wustman, B, et al. The iminosugar isofagomine increases the activity of N370S mutant acid beta-glucosidase in Gaucher fibroblasts by several mechanisms. Proc Natl Acad Sci USA. 2006;103(37):13813–8.CrossRefGoogle ScholarPubMed
Aflaki, E, Moaven, N, Borger, DK, et al. Lysosomal storage and impaired autophagy lead to inflammasome activation in Gaucher macrophages. Aging Cell. 2016;15(1):77–88.CrossRefGoogle ScholarPubMed
Tominaga, L, Ogawa, Y, Taniguchi, M, et al. Galactonojirimycin derivatives restore mutant human beta-galactosidase activities expressed in fibroblasts from enzyme-deficient knockout mouse. Brain Dev. 2001;23(5):284–7.Google Scholar
Matsuda, J, Suzuki, O, Oshima, A, et al. Chemical chaperone therapy for brain pathology in G(M1)-gangliosidosis. Proc Natl Acad Sci USA. 2003;100(26):15912–7.Google Scholar
Schalli, M, Weber, P, Tysoe, C, et al. A new type of pharmacological chaperone for GM1-gangliosidosis related human lysosomal beta-galactosidase: N-substituted 5-amino-1-hydroxymethyl-cyclopentanetriols. Bioorg Med Chem Lett. 2017;27(15):3431–5.Google Scholar
Clarke, JT, Mahuran, DJ, Sathe, S, et al. An open-label phase I/II clinical trial of pyrimethamine for the treatment of patients affected with chronic GM2 gangliosidosis (Tay–Sachs or Sandhoff variants). Mol Genet Metab. 2011;102(1):6–12.Google Scholar
Argyriou, C, D’Agostino, MD, Braverman, N. Peroxisome biogenesis disorders. Transl Sci Rare Dis. 2016;1(2):111–44.Google ScholarPubMed
Wood, PL, Khan, MA, Smith, T, et al. In vitro and in vivo plasmalogen replacement evaluations in rhizomelic chrondrodysplasia punctata and Pelizaeus–Merzbacher disease using PPI-1011, an ether lipid plasmalogen precursor. Lipids Health Dis. 2011;10:182.Google Scholar
Wei, H, Kemp, S, McGuinness, MC, Moser, AB, Smith, KD. Pharmacological induction of peroxisomes in peroxisome biogenesis disorders. Ann Neurol. 2000;47(3):286–96.Google Scholar
Li, X, Baumgart, E, Dong, GX, et al. PEX11alpha is required for peroxisome proliferation in response to 4-phenylbutyrate but is dispensable for peroxisome proliferator-activated receptor alpha-mediated peroxisome proliferation. Mol Cell Biol. 2002;22(23):8226–40.CrossRefGoogle ScholarPubMed
Dranchak, PK, Di Pietro, E, Snowden, A, et al. Nonsense suppressor therapies rescue peroxisome lipid metabolism and assembly in cells from patients with specific PEX gene mutations. J Cell Biochem. 2011;112(5):1250–8.Google Scholar
Schulz, A, Ajayi, T, Specchio, N, et al. Study of intraventricular cerliponase alfa for CLN2 disease. N Engl J Med. 2018;378(20):1898–907.Google Scholar
Meng, Y, Sohar, I, Wang, L, Sleat, DE, Lobel, P. Systemic administration of tripeptidyl peptidase I in a mouse model of late infantile neuronal ceroid lipofuscinosis: Effect of glycan modification. PLoS One. 2012;7(7):e40509.Google Scholar
Meng, Y, Sohar, I, Sleat, DE, et al. Effective intravenous therapy for neurodegenerative disease with a therapeutic enzyme and a peptide that mediates delivery to the brain. Mol Ther. 2014;22(3):547–53.Google Scholar
Boado, RJ, Pardridge, WM. The Trojan horse liposome technology for nonviral gene transfer across the blood–brain barrier. J Drug Deliv. 2011;2011:296151.CrossRefGoogle ScholarPubMed
Pardridge, WM. Molecular Trojan horses for blood–brain barrier drug delivery. Discov Med. 2006;6(34):139-43.Google Scholar
Muro, S. New biotechnological and nanomedicine strategies for treatment of lysosomal storage disorders. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2010;2(2):189–204.Google Scholar
Coutinho, MF, Santos, JI, Matos, L, Alves, S. Genetic substrate reduction therapy: A promising approach for lysosomal storage disorders. Diseases. 2016;4(4).Google Scholar
Kirkegaard, T, Gray, J, Priestman, DA, et al. Heat shock protein-based therapy as a potential candidate for treating the sphingolipidoses. Sci Transl Med. 2016;8(355):355ra118.Google Scholar
Davidson, CD, Fishman, YI, Puskas, I, et al. Efficacy and ototoxicity of different cyclodextrins in Niemann–Pick C disease. Ann Clin Transl Neurol. 2016;3(5):366–80.Google Scholar
Kuhl, JS, Suarez, F, Gillett, GT, et al. Long-term outcomes of allogeneic haematopoietic stem cell transplantation for adult cerebral X-linked adrenoleukodystrophy. Brain. 2017;140(4):953–66.Google Scholar
Kuhl, JS, Kupper, J, Baque, H, et al. Potential risks to stable long-term outcome of allogeneic hematopoietic stem cell transplantation for children with cerebral X-linked adrenoleukodystrophy. JAMA Netw Open. 2018;1(3):e180769.Google Scholar
Barth, AL, Horovitz, DDG. Hematopoietic stem cell transplantation in mucopolysaccharidosis type II: A literature review and critical analysis. J Inborn Error Metab Screen. 2018;6:2326409818779097.Google Scholar
Mercati, O, Pichard, S, Ouachee, M, et al. Limited benefits of presymptomatic cord blood transplantation in neurovisceral acid sphingomyelinase deficiency (ASMD) intermediate type. Eur J Paediatr Neurol. 2017;21(6):907–11.Google Scholar
Lonnqvist, T, Vanhanen, SL, Vettenranta, K, et al. Hematopoietic stem cell transplantation in infantile neuronal ceroid lipofuscinosis. Neurology. 2001;57(8):1411–6.Google Scholar
Lake, BD, Henderson, DC, Oakhill, A, Vellodi, A. Bone marrow transplantation in Batten disease (neuronal ceroid-lipofuscinosis). Will it work? Preliminary studies on coculture experiments and on bone marrow transplant in late infantile Batten disease. Am J Med Genet. 1995;57(2):369–73.Google Scholar
Yuza, Y, Yokoi, K, Sakurai, K, et al. Allogenic bone marrow transplantation for late-infantile neuronal ceroid lipofuscinosis. Pediatr Int. 2005;47(6):681–3.Google Scholar
Selden, NR, Al-Uzri, A, Huhn, SL, et al. Central nervous system stem cell transplantation for children with neuronal ceroid lipofuscinosis. J Neurosurg Pediatr. 2013;11(6):643–52.Google Scholar
Hu, P, Li, Y, Nikolaishvili-Feinberg, N, et al. Hematopoietic stem cell transplantation and lentiviral vector-based gene therapy for Krabbe’s disease: Present convictions and future prospects. J Neurosci Res. 2016;94(11):1152–68.Google Scholar
Wadhwa, A, Chen, Y, Holmqvist, A, et al. Late mortality after allogeneic blood or marrow transplantation for inborn errors of metabolism: A report from the Blood or Marrow Transplant Survivor Study-2 (BMTSS-2). Biol Blood Marrow Transplant. 2019;25(2):328–34.Google Scholar
Cartier, N, Hacein-Bey-Abina, S, Bartholomae, CC, et al. Lentiviral hematopoietic cell gene therapy for X-linked adrenoleukodystrophy. Methods Enzymol. 2012;507:187–98.Google Scholar
Nagabhushan Kalburgi, S, Khan, NN, Gray, SJ. Recent gene therapy advancements for neurological diseases. Discov Med. 2013;15(81):111–9.Google Scholar
Eichler, F, Duncan, C, Musolino, PL, et al. Hematopoietic stem-cell gene therapy for cerebral adrenoleukodystrophy. N Engl J Med. 2017;377(17):1630–8. doi:10.1056/NEJMoa1700554. Epub 2017 Oct 4.Google Scholar
Chien, YH, Lee, NC, Tseng, SH, et al. Efficacy and safety of AAV2 gene therapy in children with aromatic L-amino acid decarboxylase deficiency: An open-label, phase 1/2 trial. Lancet Child Adolesc Health. 2017;1(4):265–73.Google Scholar
Perez, B, Gutierrez-Solana, LG, Verdu, A, et al. Clinical, biochemical, and molecular studies in pyridoxine-dependent epilepsy. Antisense therapy as possible new therapeutic option. Epilepsia. 2013;54(2):239–48.Google Scholar
Yin, H, Xue, W, Chen, S, et al. Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype. Nat Biotechnol. 2014;32(6):551–3.Google Scholar
Yin, H, Song, CQ, Dorkin, JR, et al. Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo. Nat Biotechnol. 2016;34(3):328–33.Google Scholar
Pankowicz, FP, Barzi, M, Legras, X, et al. Reprogramming metabolic pathways in vivo with CRISPR/Cas9 genome editing to treat hereditary tyrosinaemia. Nat Commun. 2016;7:12642.Google Scholar
Nygaard, S, Barzel, A, Haft, A, et al. A universal system to select gene-modified hepatocytes in vivo. Sci Transl Med. 2016;8(342):342ra79.Google Scholar
Yang, Y, Wang, L, Bell, P, et al. A dual AAV system enables the Cas9-mediated correction of a metabolic liver disease in newborn mice. Nat Biotechnol. 2016;34(3):334–8.Google Scholar
Sharma, R, Anguela, XM, Doyon, Y, et al. In vivo genome editing of the albumin locus as a platform for protein replacement therapy. Blood. 2015;126(15):1777–84.Google Scholar
Brooks, DA, Muller, VJ, Hopwood, JJ. Stop-codon read-through for patients affected by a lysosomal storage disorder. Trends Mol Med. 2006;12(8):367–73.Google Scholar
Miller, JN, Chan, CH, Pearce, DA. The role of nonsense-mediated decay in neuronal ceroid lipofuscinosis. Hum Mol Genet. 2013;22(13):2723-34.Google Scholar
Ho, G, Reichardt, J, Christodoulou, J. In vitro read-through of phenylalanine hydroxylase (PAH) nonsense mutations using aminoglycosides: A potential therapy for phenylketonuria. J Inherit Metab Dis. 2013;36(6):955–9.Google Scholar
Medina, DL, Fraldi, A, Bouche, V, et al. Transcriptional activation of lysosomal exocytosis promotes cellular clearance. Dev Cell. 2011;21(3):421–30.Google Scholar
Song, W, Wang, F, Savini, M, et al. TFEB regulates lysosomal proteostasis. Hum Mol Genet. 2013;22(10):1994–2009.Google Scholar
Moskot, M, Montefusco, S, Jakobkiewicz-Banecka, J, et al. The phytoestrogen genistein modulates lysosomal metabolism and transcription factor EB (TFEB) activation. J Biol Chem. 2014;289(24):17054–69.Google Scholar
Xu, M, Liu, K, Swaroop, M, et al. delta-Tocopherol reduces lipid accumulation in Niemann–Pick type C1 and Wolman cholesterol storage disorders. J Biol Chem. 2012;287(47):39349–60.Google Scholar
Hensley, K, Venkova, K, Christov, A, Gunning, W, Park, J. Collapsin response mediator protein-2: An emerging pathologic feature and therapeutic target for neurodisease indications. Mol Neurobiol. 2011;43(3):180–91.Google Scholar
Khanna, R, Wilson, SM, Brittain, JM, et al. Opening Pandora’s jar: A primer on the putative roles of CRMP2 in a panoply of neurodegenerative, sensory and motor neuron, and central disorders. Future Neurol. 2012;7(6):74–71.Google Scholar
Hensley, K, Christov, A, Kamat, S, et al. Proteomic identification of binding partners for the brain metabolite lanthionine ketimine (LK) and documentation of LK effects on microglia and motoneuron cell cultures. J Neurosci. 2010;30(8):2979–88.Google Scholar
Beyreuther, BK, Freitag, J, Heers, C, et al. Lacosamide: A review of preclinical properties. CNS Drug Rev. 2007;13(1):21–42.CrossRefGoogle ScholarPubMed
Sarkar, C, Chandra, G, Peng, S, et al. Neuroprotection and lifespan extension in Ppt1(-/-) mice by NtBuHA: Therapeutic implications for INCL. Nat Neurosci. 2013;16(11):1608–17.Google Scholar
Lara, MC, Weiss, B, Illa, I, et al. Infusion of platelets transiently reduces nucleoside overload in MNGIE. Neurology. 2006;67(8):1461–3.Google Scholar
Hussein, E. Non-myeloablative bone marrow transplant and platelet infusion can transiently improve the clinical outcome of mitochondrial neurogastrointestinal encephalopathy: A case report. Transfus Apher Sci. 2013;49(2):208–11.Google Scholar
Moran, NF, Bain, MD, Muqit, MM, Bax, BE. Carrier erythrocyte entrapped thymidine phosphorylase therapy for MNGIE. Neurology. 2008;71(9):686–8.Google Scholar
Levene, M, Coleman, DG, Kilpatrick, HC, et al. Preclinical toxicity evaluation of erythrocyte-encapsulated thymidine phosphorylase in BALB/c mice and beagle dogs: An enzyme-replacement therapy for mitochondrial neurogastrointestinal encephalomyopathy. Toxicol Sci. 2013;131(1):311–24.Google Scholar
Camara, Y, Gonzalez-Vioque, E, Scarpelli, M, et al. Administration of deoxyribonucleosides or inhibition of their catabolism as a pharmacological approach for mitochondrial DNA depletion syndrome. Hum Mol Genet. 2014;23(9):2459–67.Google Scholar
Garone, C, Garcia-Diaz, B, Emmanuele, V, et al. Deoxypyrimidine monophosphate bypass therapy for thymidine kinase 2 deficiency. EMBO Mol Med. 2014;6(8):1016–27.Google Scholar
Cerutti, R, Pirinen, E, Lamperti, C, et al. NAD(+)-dependent activation of Sirt1 corrects the phenotype in a mouse model of mitochondrial disease. Cell Metab. 2014;19(6):1042–9.CrossRefGoogle Scholar
Viscomi, C, Bottani, E, Civiletto, G, et al. In vivo correction of COX deficiency by activation of the AMPK/PGC-1alpha axis. Cell Metab. 2011;14(1):80–90.Google Scholar
Khan, NA, Auranen, M, Paetau, I, et al. Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3. EMBO Mol Med. 2014;6(6):721–31.Google Scholar
Wenz, T, Diaz, F, Spiegelman, BM, Moraes, CT. Activation of the PPAR/PGC-1alpha pathway prevents a bioenergetic deficit and effectively improves a mitochondrial myopathy phenotype. Cell Metab. 2008;8(3):249–56.Google Scholar
Bastin, J, Lopes-Costa, A, Djouadi, F. Exposure to resveratrol triggers pharmacological correction of fatty acid utilization in human fatty acid oxidation-deficient fibroblasts. Hum Mol Genet. 2011;20(10):2048–57.Google Scholar
Yiu, EM, Tai, G, Peverill, RE, et al. An open-label trial in Friedreich ataxia suggests clinical benefit with high-dose resveratrol, without effect on frataxin levels. J Neurol. 2015;262(5):1344–53.Google Scholar
Felici, R, Cavone, L, Lapucci, A, et al. PARP inhibition delays progression of mitochondrial encephalopathy in mice. Neurotherapeutics. 2014;11(3):651–64.Google Scholar
DeVay, RM, Dominguez-Ramirez, L, Lackner, LL, et al. Coassembly of Mgm1 isoforms requires cardiolipin and mediates mitochondrial inner membrane fusion. J Cell Biol. 2009;186(6):793–803.Google Scholar
Dassa, EP, Dufour, E, Goncalves, S, et al. Expression of the alternative oxidase complements cytochrome C oxidase deficiency in human cells. EMBO Mol Med. 2009;1(1):30–6.Google Scholar
Fernandez-Ayala, DJ, Sanz, A, Vartiainen, S, et al. Expression of the Ciona intestinalis alternative oxidase (AOX) in Drosophila complements defects in mitochondrial oxidative phosphorylation. Cell Metab. 2009;9(5):449–60.Google Scholar
Kim, J, Kundu, M, Viollet, B, Guan, KL. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol. 2011;13(2):132–41.Google Scholar
Peng, M, Ostrovsky, J, Kwon, YJ, et al. Inhibiting cytosolic translation and autophagy improves health in mitochondrial disease. Hum Mol Genet. 2015;24(17):4829–47.Google Scholar
Ma, H, Folmes, CD, Wu, J, et al. Metabolic rescue in pluripotent cells from patients with mtDNA disease. Nature. 2015;524(7564):234–8.Google Scholar
Gammage, PA, Rorbach, J, Vincent, AI, Rebar, EJ, Minczuk, M. Mitochondrially targeted ZFNs for selective degradation of pathogenic mitochondrial genomes bearing large-scale deletions or point mutations. EMBO Mol Med. 2014;6(4):458–66.Google Scholar
Bacman, SR, Williams, SL, Pinto, M, Peralta, S, Moraes, CT. Specific elimination of mutant mitochondrial genomes in patient-derived cells by mitoTALENs. Nat Med. 2013;19(9):1111–3.Google Scholar
Hsu, PD, Lander, ES, Zhang, F. Development and applications of CRISPR–Cas9 for genome engineering. Cell. 2014;157(6):1262–78.Google Scholar
Cox, DB, Platt, RJ, Zhang, F. Therapeutic genome editing: Prospects and challenges. Nat Med. 2015;21(2):121–31.Google Scholar
Reddy, P, Ocampo, A, Suzuki, K, et al. Selective elimination of mitochondrial mutations in the germline by genome editing. Cell. 2015;161(3):459–69.Google Scholar
Hornig-Do, HT, Montanari, A, Rozanska, A, et al. Human mitochondrial leucyl tRNA synthetase can suppress non cognate pathogenic mt-tRNA mutations. EMBO Mol Med. 2014;6(2):183–93.Google Scholar
Perli, E, Giordano, C, Pisano, A, et al. The isolated carboxy-terminal domain of human mitochondrial leucyl-tRNA synthetase rescues the pathological phenotype of mitochondrial tRNA mutations in human cells. EMBO Mol Med. 2014;6(2):169–82.Google Scholar
Di Meo, I, Auricchio, A, Lamperti, C, et al. Effective AAV-mediated gene therapy in a mouse model of ethylmalonic encephalopathy. EMBO Mol Med. 2012;4(9):1008–14.CrossRefGoogle Scholar
Torres-Torronteras, J, Viscomi, C, Cabrera-Perez, R, et al. Gene therapy using a liver-targeted AAV vector restores nucleoside and nucleotide homeostasis in a murine model of MNGIE. Mol Ther. 2014;22(5):901–7.Google Scholar
Bottani, E, Giordano, C, Civiletto, G, et al. AAV-mediated liver-specific MPV17 expression restores mtDNA levels and prevents diet-induced liver failure. Mol Ther. 2014;22(1):10-7.CrossRefGoogle ScholarPubMed
Yu, H, Koilkonda, RD, Chou, TH, et al. Gene delivery to mitochondria by targeting modified adenoassociated virus suppresses Leber’s hereditary optic neuropathy in a mouse model. Proc Natl Acad Sci USA. 2012;109(20):E1238–47.CrossRefGoogle ScholarPubMed
Wan, X, Pei, H, Zhao, MJ, et al. Efficacy and safety of rAAV2-ND4 treatment for Leber’s hereditary optic neuropathy. Sci Rep. 2016;6:21587.Google Scholar
Kurian, MA, Gissen, P, Smith, M, Heales, S, Jr., Clayton, PT. The monoamine neurotransmitter disorders: An expanding range of neurological syndromes. Lancet Neurol. 2011;10(8):721–33.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×