Rare Nephrology News
Tuberous sclerosis complex
Tuberous sclerosis complex (TSC) is characterized by the growth of benign tumors throughout the body, including in the heart, brain, and kidneys
Age of Onset
Tuberous sclerosis (also called tuberous sclerosis complex, or TSC) is a rare, multi-system genetic disease that causes benign tumors to grow in the brain and on other vital organs such as the kidneys, heart, eyes, lungs, and skin. It usually affects the central nervous system and can result in a combination of symptoms including seizures, impaired intellectual development, autism, behavioral problems, skin abnormalities, and kidney disease.
The severity of symptoms varies widely. Symptoms range from mild—allowing people to live independent, productive lives—to more severe symptoms that can affect everyday life and even be life-threatening.
Tuberous sclerosis complex
60% of tuberous sclerosis cases are diagnosed in the first year. Diagnosis slows down considerably after the first year.
5 Facts you should know
TSC causes a combination of symptoms including seizures, intellectual disability, developmental delay, behavioral problems, skin abnormalities, lung disease, and kidney disease.
The physical manifestations of TSC are due to the formation of hamartia, hamartomas (benign growths such as facial angiofibroma and subependymal nodules), and very rarely, cancerous hamartoblastomas.
Three types of brain tumors are associated with TSC: giant cell astrocytomas, cortical tubers, and subependymal nodules.
About 90% of people with TSC develop a range of neurodevelopmental, behavioral, psychiatric, and psychosocial difficulties.
Around 80% of children under two years old with TSC have at least one cardiac rhabdomyoma, and about 90% of those will have several.
Interest over time
Common signs & symptoms
Small bumps made up of blood vessels (angiofibromas)
Patches of thickened, rough skin (shagreen patches)
Growths under the fingernails and toenails (ungual fibromas)
Light colored skin patches (hypomelanonic macules)
Benign brain tumor (astrocytoma)
Abnormal organization of the brain (cortical dysplasia)
Nodules in the brain (subependymal nodules)
Everolimus (Brand name: Afinitor)
Manufactured by Novartis Pharmaceuticals Corporation
FDA-approved indication: April 2018 approved for the adjunctive treatment of adult and pediatric patients age 2 years and older with tuberous sclerosis complex (TSC)-associated partial-onset seizures. April 2012 approved for the treatment of adults with renal angiomyolipoma and tuberous sclerosis complex (TSC) not requiring immediate surgery. October 2010 approved for the treatment of patients with subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis who require therapeutic intervention but are not candidates for curative surgical resection.
Vigabatrin (Brand name: Sabril)
Manufactured by Lundbeck
FDA-approved indication: For infantile spasms (IS) 1 month to 2 years of age.
Epidiolex (cannabidiol) [CBD] oral solution is FDA approved for the treatment of seizures associated with tuberous sclerosis complex (TSC) in patients one year of age and older. Epidiolex was previously approved for the treatment of seizures associated with two rare and severe forms of epilepsy, Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS). This is the only FDA-approved drug that contains a purified drug substance derived from cannabis. It is also the second FDA approval of a drug for the treatment of seizures associated with TSC.
CBD is a chemical component of the Cannabis sativa plant. However, CBD does not cause intoxication or euphoria (the “high”) that comes from tetrahydrocannabinol (THC). It is THC (and not CBD) that is the primary psychoactive component of cannabis.
Top Clinical Trials
|Safety, Pharmacokinetics, and Exploratory Efficacy Assessment of Adjunctive Cannabidiol Oral Solution (GWP42003-P) Compared With Standard of Care Antiseizure Medication, in Participants Age 1 Month to <12 Months of Age With Tuberous Sclerosis Complex Who Experience Inadequately-controlled Seizures||This study will be conducted to evaluate the safety, tolerability, and pharmacokinetics of GWP42003-P compared with standard of care (SOC) antiseizure medication (ASM), assessed during the 17-week treatment period.||Phase 3||Recruiting||Drug: GWP42003-P|Drug: SOC||More Info|
|Dose-Ranging Efficacy and Safety Study of Topical Rapamycin Cream for Facial Angiofibroma Associated With Tuberous Sclerosis Complex||The study aims to compare the safety and efficacy of two different strengths of Rapamycin cream, topical and placebo over 26 weeks in the treatment of facial angiofibroma (FA) associated with Tuberous Sclerosis Complex (TSC).||Phase 2|Phase 3||Recruiting||Drug: rapamycin|Drug: placebo||More Info|
|Topical Sirolimus Ointment for Cutaneous Angiofibromas in Subjects With Tuberous Sclerosis Complex||The objective of this study is to evaluate the safety and efficacy of sirolimus (0.2% and 0.4% formulations) and its vehicle when applied topically once daily for 12 weeks for the treatment of cutaneous angiofibromas in pediatric subjects with tuberous sclerosis complex (TSC).||Phase 2||Recruiting||Drug: Sirolimus 0.2%|Drug: Sirolimus 0.4%|Drug: Placebo ointment||More Info|
|Stopping TSC Onset and Progression 2B: Sirolimus TSC Epilepsy Prevention Study||This trial is a Phase II randomized, double-blind, placebo controlled multi-site study to evaluate the safety and efficacy of early sirolimus to prevent or delay seizure onset in TSC infants.||Phase 2||Recruiting||Drug: Sirolimus|Drug: Placebo||More Info|
|A Study to Evaluate Efficacy and Safety of Vatiquinone for Treating Mitochondrial Disease in Participants With Refractory Epilepsy||This is a parallel-arm, double-blind, placebo-controlled study with a screening phase that includes a 28-day run-in phase to establish baseline seizure frequency, followed by a 24-week, randomized, placebo-controlled phase. After completion of the randomized, placebo-controlled phase, participants may enter a 48-week, long-term, extension phase during which they will receive open-label treatment with vatiquinone.||Phase 2|Phase 3||Recruiting||Drug: Vatiquinone|Other: Placebo||More Info|
Top Treatments in Research
|Agent||Class/Mechanism of Action||Development Status||Company||Clinical Studies||More Information|
|Drug: GWP42003 (Epidiolex) for pediatric patients||As is the case for many other AEDs, the exact MOA by which CBD produces its anticonvulsant effects is unknown. Cannabidiol is a structurally novel anti-convulsant. Cannabidiol does not exert its anti-convulsant effects through CB1 receptors, nor through voltage-gated sodium channels. CBD may exert a cumulative anti-convulsant effect, modulating a number of endogenous systems including, but not limited to neuronal inhibition (synaptic and extrasynaptic GABA channels), modulation of intracellular calcium (TRPV, VDAC, GPR55), and possible anti-inflammatory effects (adenosine). CBD does not directly bind to, nor activate, CB1 and CB2 receptors at concentrations pharmacologically relevant to its anticonvulsant effect. Among the likely mechanisms of action, modulation of intra-cellular calcium via GPR-55, TRPV, and VDAC is under active investigation in our research laboratories. Additional mechanisms under exploration by our researchers include adenosine modulation, glycine and GABAergic modulation, and serotonin agonism.||Phase 3||GW Research Ltd||More Info||More Info|
|Drug: Sirolimus||Sirolimus has potent immunosuppressive properties reflecting its ability to disrupt cytokine signaling that promotes lymphocyte growth and differentiation. In IL-2-stimulated T cells, sirolimus impedes progression through the G1/S transition of the proliferation cycle, resulting in a mid-to-late G1 arrest.||Phase 2||Aucta Pharmaceuticals, Inc||More Info||More Info|
|Drug: Vatiquinone||The mechanism of action of EPI-743 involves augmenting the synthesis of glutathione, optimizing metabolic control, enhancing the expression of genetic elements critical for cellular management of oxidative stress, and acting at the mitochondria to regulate electron transport.||Phase 2|Phase 3||PTC Therapeutics||More Info||More Info|
|Drug: Ganaxolone||Ganaxolone is a GABAA receptor modulator that acts by regulating brain activity. This process can include inhibiting the abnormal electrical discharges that cause seizures and status epilepticus or restoring balance in disrupted neuronal activity in other CNS disorders.||Phase 2||Marinus Pharmaceuticals, Inc.||More Info||More Info|