Sirolimus Used During Pregnancy in a Living Related Renal Transplant Recipient: A Case Report

Chu, Shih-Ming; Liu, K.-L.; Chiang, Yang‐Jen; Wang, Hsu-Han; Lai, Ping-Chin

doi:10.1016/j.transproceed.2008.06.015

Cited by 47 publications

(23 citation statements)

References 4 publications

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“…Previous clinical case studies with rapamycin during pregnancy have not demonstrated any adverse outcomes to mother or child (Chu et al 2008; Framarino dei Malatesta et al 2011) while previous studies from our laboratory demonstrated significant survival benefit of prenatal treatment of a severe mouse brain model in which Tsc1 is deleted in neural progenitor cells (Anderl et al 2011). In addition, during preparation of this manuscript, a study of a mouse model of Tsc2 , evaluating the effects of prenatal and postnatal rapamycin treatment noted that daily rapamycin administration beginning at E12.5 resulted in hippocampal dependent learning impairments when compared to treatment started postnatally in this Tsc2 model (Way et al 2012).…”

Section: Discussionmentioning

confidence: 79%

Prenatal Rapamycin Results in Early and Late Behavioral Abnormalities in Wildtype C57Bl/6 Mice

et al. 2012

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Mammalian target of rapamycin (mTOR) signaling has been shown to be deregulated in a number of genetic, neurodevelopmental disorders including Tuberous Sclerosis Complex, Neurofibromatosis, Fragile X, and Rett syndromes. As a result, mTOR inhibitors, such as rapamycin and its analogs, offer potential therapeutic avenues for these disorders. Some of these disorders – such as Tuberous Sclerosis Complex – can be diagnosed prenatally. Thus, prenatal administration of these inhibitors could potentially prevent the development of the devastating symptoms associated with these disorders. To assess the possible detrimental effects of prenatal rapamycin treatment, we evaluated both early and late behavioral effects of a single rapamycin treatment at embryonic day 16.5 in wildtype C57Bl/6 mice. This treatment adversely impacted early developmental milestones as well as motor function in adult animals. Rapamycin also resulted in anxiety-like behaviors during both early development and adulthood but did not affect adult social behaviors. Together, these results indicate that a single, prenatal rapamycin treatment not only adversely affects early postnatal development but also results in long lasting negative effects, persisting into adulthood. These findings are of importance in considering prenatal administration of rapamycin and related drugs in the treatment of patients with neurogenetic, neurodevelopmental disorders.

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Section: Discussionmentioning

confidence: 79%

Prenatal Rapamycin Results in Early and Late Behavioral Abnormalities in Wildtype C57Bl/6 Mice

et al. 2012

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“…Difficulty with weight gain during prolonged postnatal treatment with rapamycin has also been seen in other mouse models [22,23,28,29,36]. Limited data on safety of prenatal exposure to rapamycin in humans largely stems from transplant patients on rapamycin for immune suppression [59–61]. In these handful of case reports and seven women reported to the National Transplantation Pregnancy Registry, rapamycin does not appear to be associated with any specific birth defects although 3 of seven pregnancies resulted in first trimester spontaneous abortions.…”

Section: Discussionmentioning

confidence: 99%

Mammalian Target of Rapamycin (mTOR) Inhibition: Potential for Antiseizure, Antiepileptogenic, and Epileptostatic Therapy

Ryther

Wong

2012

Curr Neurol Neurosci Rep

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New epilepsy treatments are needed that not only inhibit seizures symptomatically (antiseizure) but also prevent the development of epilepsy (antiepileptogenic). The mammalian target of rapamycin (mTOR) pathway may mediate mechanisms of epileptogenesis and serve as a rational therapeutic target. mTOR inhibitors have antiepileptogenic and antiseizure effects in animal models of the genetic disease, tuberous sclerosis complex. The mTOR pathway is also implicated in epileptogenesis in animal models of acquired epilepsy and infantile spasms, although the effects of mTOR inhibitors are variable depending on the specific conditions and model. Furthermore, beneficial effects on seizures are lost when treatment is withdrawn, suggesting that mTOR inhibitors are “epileptostatic” in only stalling epilepsy progression during treatment. Clinical studies of rapamycin in human epilepsy are limited, but suggest that mTOR inhibitors at least have antiseizure effects in tuberous sclerosis patients. Further studies are needed to assess the full potential of mTOR inhibitors for epilepsy treatment.

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“…We preemptively avoid mycophenolate mofetil and sirolimus based on data and limited experience in this population, respectively (67,68). Steroids and azathioprine have a long history in transplantation.…”

Section: For Patients Interested In Becoming Pregnant After Transplanmentioning

confidence: 99%

Topics in Transplantation Medicine for General Nephrologists

Obhrai

Leach

Gaumond

et al. 2010

Clinical Journal of the American Society of Nephrology

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Before transplantation, the general nephrologist is the primary resource for potential kidney transplantation recipients. After transplantation, the general nephrologist is increasingly managing transplant medications and complications. We provide evidence-based management strategies for common clinical issues. Linking our approach with the data allows the clinician to explore each subject in greater depth to tailor care to individual patients.

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Sirolimus Used During Pregnancy in a Living Related Renal Transplant Recipient: A Case Report

Cited by 47 publications

References 4 publications

Prenatal Rapamycin Results in Early and Late Behavioral Abnormalities in Wildtype C57Bl/6 Mice

Prenatal Rapamycin Results in Early and Late Behavioral Abnormalities in Wildtype C57Bl/6 Mice

Mammalian Target of Rapamycin (mTOR) Inhibition: Potential for Antiseizure, Antiepileptogenic, and Epileptostatic Therapy

Topics in Transplantation Medicine for General Nephrologists

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