Efficacy and safety of mTOR inhibitors (rapamycin and its analogues) for tuberous sclerosis complex: a meta-analysis

Li, Min; Zhou, Ying; Chen, Chaoyang; Yang, Ting; Zhou, Shuang; Chen, Shuqing; Wu, Ye; Chen, Yimin

doi:10.1186/s13023-019-1012-x

Cited by 73 publications

(61 citation statements)

References 37 publications

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“…Rapamycin, a drug which directly interacts with mTOR, blocks its signaling effects and was shown to exhibit antiproliferative effects specifically on immune cells leading to its approval as immunosuppressive drug [42]. Consistent with the aforementioned concept, recent clinical studies reveal a significant decrease in inflammation and senescence markers in patients after treatment with mTOR inhibitors [24].…”

Section: Signaling and Targeting Of Resistance And Tolerancementioning

confidence: 80%

Die zelluläre Basis des Organversagens bei Sepsis – Signalwege in Gewebeschädigung und Reparaturprozessen

Bauer

Wetzker

2020

Med Klin Intensivmed Notfmed

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Section: Signaling and Targeting Of Resistance And Tolerancementioning

confidence: 80%

Die zelluläre Basis des Organversagens bei Sepsis – Signalwege in Gewebeschädigung und Reparaturprozessen

Bauer

Wetzker

2020

Med Klin Intensivmed Notfmed

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“…mTOR inhibitors have been groundbreaking in the TSC world due to their ability to target the molecular defect in the disorder. However, animal models and clinical studies have shown that not all TSC-related symptoms benefit from mTOR inhibitors to the same extent [94]. Research is still ongoing for the optimization of mTOR inhibition for each symptom and what other pharmacologic and nonpharmacologic approaches could be employed for tackling the challenges in TSC.…”

Section: Treatment Optionsmentioning

confidence: 99%

Tuberous sclerosis: a review of the past, present, and future

Uysal¹,

Şahin²

2020

Turk J Med Sci

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Tuberous sclerosis complex (TSC) is an autosomal dominant, multisystem disorder that is characterized by cellular and tissue dysplasia in several organs. With the advent of genetic and molecular techniques, mutations in the TSC1 or TSC2 genes were discovered to be responsible for mTOR overactivation, which is the underlying mechanism of pathogenesis. TSC is a highly heterogenous clinical entity with variable presentations and severity of disease. The brain, heart, skin, eyes, kidneys, and lungs are commonly involved in this syndrome, with neurologic symptoms comprising a significant source of morbidity and mortality. In 2012, the diagnostic criteria for TSC were revised by the International Tuberous Sclerosis Complex Consensus panel, and genetic testing was incorporated into the guidelines. Early detection of cardiac rhabdomyomas or TSC-associated skin lesions can suggest the diagnosis and underlie the importance of clinical vigilance. Animal studies have demonstrated the benefit of using mTOR inhibitors for various symptoms of TSC, and they have been successfully translated into clinical trials with significant improvement in symptom burden. Subependymal giant cell astrocytomas, renal angiomyolipomas, and epilepsy are the three FDA-approved indications in relation to TSC for the use of everolimus, which is a first generation mTOR inhibitor. Rapamycin has been FDA approved for lymphangioleiomyomatosis. Other TSC symptoms that could potentially benefit from this class of medication are currently under investigation. TSC constitutes a unique combination of protean physical symptoms and neurobehavioral abnormalities. TSC associated neuropsychiatric disorders (TAND), including intellectual disability, mood disorders, and autism spectrum disorder, represent significant challenges but remain underdiagnosed and undertreated. The TAND checklist is a useful tool for routine use in the clinical evaluation of TSC patients. A multidisciplinary treatment plan, based on the specific problems and needs of individuals, is the key to management of this genetic condition. Ongoing research studies have been providing promising leads for developing novel mechanistic strategies to address the pathophysiology of TSC.

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“…48,49 A recent comprehensive review by Li et al has shown that seizure frequency is significantly reduced in patients with TS given mTOR inhibitors. 50 mTOR inhibition should be the subject of future trials as this therapeutic modality addresses the potentially lethal complications of TS including subependymal giant cell astrocytoma related hydrocephalus, hemorrhage due to renal angiomyolipoma and progressive lymphangioleiomyomatosis, besides seizure control. 51…”

Section: Mtor Inhibitors For Tuberous Sclerosismentioning

confidence: 99%

Management of Infantile Spasms: An Updated Review

Iype

Koshy

2020

International Journal of Epilepsy

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Infantile spasms remain the most challenging of the epileptic encephalopathies of childhood. Infantile spasms are classified as an epileptic encephalopathy, as the adverse cognitive and behavioral burden of the condition is out of proportion to the burden one would expect from the underlying etiology or the accompanying magnetic resonance imaging. The ictal and interictal electroencephalographic (EEG) activity is presumed to contribute to the progressive cerebral dysfunction. In many of these children, the underlying etiology also contributes to the severe mental subnormality and autistic behavior. Though it is the syndromic approach that guides the pediatric epileptologist, it is best to keep in mind that one syndrome may evolve into another in infancy and early childhood. A baby with Ohtahara syndrome may, after 2 to 7 months, begin to have spasms. Lennox-Gastaut syndrome with its typical seizure types and EEG may evolve in a child with infantile spasms.The unique modalities used in the treatment of infantile spasms make early recognition important. It is, however, also of paramount importance to make an etiological diagnosis as the underlying etiology may be eminently treatable. The treating physician cannot abandon them as wholly “intractable” epilepsy. The excellent response to treatment in the few who just cannot be defined or accurately predicted drives the physician to exercise his brain. Use of the two well-accepted modalities of treatment; vigabatrin and adrenocorticotrophic hormone singly or in combination, oral steroids in high dose, ketogenic diet, the conventional antiepileptic medications, and strategies to target the basic cause have been tried out by various clinicians. Here, we have made an attempt to collate evidence and describe the progress in the management of infantile spasms.

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Efficacy and safety of mTOR inhibitors (rapamycin and its analogues) for tuberous sclerosis complex: a meta-analysis

Cited by 73 publications

References 37 publications

Die zelluläre Basis des Organversagens bei Sepsis – Signalwege in Gewebeschädigung und Reparaturprozessen

Die zelluläre Basis des Organversagens bei Sepsis – Signalwege in Gewebeschädigung und Reparaturprozessen

Tuberous sclerosis: a review of the past, present, and future

Management of Infantile Spasms: An Updated Review

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