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The understanding of how to treat neuroinflammatory disorders is dependent upon a clear understanding of the mechanisms of disease, which are only recently becoming clear.

One of the most significant advances has been discovery of autoantibody biomarkers which define treatable autoimmune encephalitis and autoimmune demyelination syndromes such as autoantibodies against NMDA-receptor, myelin oligodendrocyte glycoprotein and aquaporin-4. Although corticosteroids remain an essential part of early treatment as they reduce inflammation quickly, the therapeutic options are increasing due to our improved understanding of disease. Intravenous immunoglobulin is a useful anti-inflammatory therapy, although its mechanisms is broad, and its effects may vary from disease to disease. Plasma exchange is more stratght forward, as it removes pathogenic autoantibodies and other inflammatory proteins. Therapies which target B cell linage such as rituximab are increasingly used in autoimmune neurology, and there is recent scientific data showing that targeting CD20 B cells can be therapeutically effective in autoantibody syndromes. Recent understanding that complement plays a major role in aquaporin-4 NMOSD has resulted in the use of complement targting drugs such as eculizumab. Likewise, tocilizumab which targets interleukin 6 is an increasingly interesting option in autoimmune encephalitis patients who fail rituximab, and other neuroinflammatory disodrers which are not 'autoantibody mediated'.

Neuroinflammation can take other forms, and there is increasing interest in epigenetic immune dysfunction, and therefore the use of epigenetic therapeutics, which opens up the potential opportunity of repurposong drugs which are epigenetic modulators such as ketogenic diet, cannabidiol, and valproate, amongst many.

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Molecular treatments this group of disorders is approaching. Just to name a few: X-linked myotubular myopathy, myotonic dystrophy, , Limb-girdle dystrophies and so on. The most advances are for Duchenne muscular dystrophy. Ataluren has now been approved by several countries. This is a mutation specific therapy (“stop codon read through”), affecting approximately 15% of the DMD population, and is an oral molecule taken daily. It is considered as a ‘disease modifying molecule’, hence should not be considered as a cure. Other therapeutic approaches currently tested in clinical trials include: mutation-specific strategies aiming to correct the underlying genetic cause of the disease (e.g. exon skipping). Eteplirsen is an antisense-oligonucleotide to skip exon 51 of the DMD gene. It is available on the market, however with reservations related to efficacy. Other anti-sense oligonucleotide drugs in the pipeline are Casimersen for exon 45, Golodirsen for exon 53, and Suvodirsen for exon 51 skipping, respectively. Among these Viltolarsen has been in the forefront with a backbone publication. Gene therapy can be considered on the horizon. . One example is the micro-dystrophin gene delivered in AAV9 virus. Since 2018 four boys aged 4-6 were treated with gene therapy with an admirable improvement rate of 25-30% from the baseline. Curently there is a new series of boys with more than 60 subjects and this is ongoing. However, there are multi-fold hurdles with gene therapy to include the timing, dosage, remainings of the viral vector, burden on innate immunity, and availablity on national levels.

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Current pharmacologic and genetic therapies in mitochondrial disorders include mitochondrial redox modulators, nucleoside therapy, vitamins/cofactors, mitochondrial biogenesis enhancers, AAV-mediated gene therapy, metabolic remodeling, phospholipid stabilizers and NAD+ modulators. (1) In MELAS, there is early evidence that IV L-arginine should be administered in the acute setting of stroke-like episodes (SLEs) for reversal and that daily use of oral L-Arg may prevent frequency and severity of SLEs. (2) In Leigh syndrome (LS), the potent antioxidant EPI-743 (para-benzoquinone analog) has been shown to significantly increase reduced glutathione in lymphocytes and to reverse disease progression with improved clinical outcome in comparison to the natural history of LS. (3) In Ethylmalonic acid encephalopathy due to mutations in the ETHE1 gene, in which there is accumulation of H₂S accelerating COX inhibition in brain, the GI tract and peripheral blood vessels, the clinical phenotype is improved with the antioxidant N-acetylcysteine to buffer H₂S and metronidazole to clear intestinal anaerobic bacteria producing H₂S in the gut. (4) In mitochondrial neuro-gastrointestinal encephalomyopathy (MNGIE) syndrome due to thymidine phosphorylase deficiency, toxicity is related to the accumulation of thymidine and deoxyuridine leading to mtDNA instability. Therapies include allogenic hematopoietic stem cell transplantation, liver transplantation and erythrocyte-encapsulated thymidine phosphorylase with gene therapy in preclinical stages. (5) In LHON, early idebenone therapy has been approved in Europe. Other trials include EPI-743 and rAAV2-ND4 gene therapy in individuals who exhibit a “ window of opportunity” for directed ocular therapy. (6) Supplementation of nucleosides in mtDNA depletion syndromes is needed in TK2 and DGK deficiency.