May 15 - Tuberous Sclerosis Complex (TSC) Global Awareness Day

May 15 is World Tuberous Sclerosis Day, which aims to raise public awareness of this serious disease and to counteract social exclusion and stigmatization of people affected by it. Tuberous sclerosis, also known as Tuberous Sclerosis Complex (TSC) or Bourneville-Pringle disease, is a rare disease from the group of so-called neurocutaneous disorders.

TSC is caused by a mutation in the TSC1 or TSC2 genes, which encode important components of a protein complex that controls the activity of a regulator of cell metabolism - mammalian target of rapamycin (mTOR). It is estimated that one in six thousand people are born with such a mutation. The clinical picture of TSC varies greatly, and it can present in different ways, even in people with the same mutation. The most common manifestations of TSC include benign tumors of the brain (called cortical tubers or subependymal giant cell astrocytoma - SEGA), skin, or kidneys. Approximately 90% of patients suffer from epilepsy, often drug-resistant, occurring very early in life. In addition, an important aspect of TSC are the so-called TANDs (TSC Associated Neuropsychiatric Disorders) involving intellectual disability, autism spectrum disorders) which occur in varying severity and combination in a large proportion of patients. These neurological symptoms (e.g., epilepsy or SEGA) pose the greatest threat to patients' lives in early childhood. As they enter adulthood, the situation changes and kidney tumors become the greatest threat, in the worst case, forcing the need for a transplant.

Treatment of TSC is largely symptomatic and symptom-specific. A good example is the treatment of epilepsy, which uses drugs and approaches commonly used to treat childhood epilepsy. A major change in the treatment of patients has been the introduction of rapamycin and its derivatives, which reduce levels of mTOR activity, into the clinic. For the treatment of SEGA tumors, rapamycin has almost completely replaced surgical treatment. In epilepsy, on the other hand, it is an important complementary drug in the most severe cases. However, both clinical and basic research is still ongoing worldwide to better understand the molecular processes in patients' cells, which would allow the identification of new therapeutic targets. Moreover, it is necessary to search for new biomarkers that would help physicians to better predict, at the earliest possible stages, how TSC will develop in individual patients.

Poland is a very important center for TSC research in the world. This is due to the vibrant activities of clinical centers such as the Children's Memorial Health Institute, the Medical University of Warsaw, the Medical University of Lodz, and patient organizations. Among the most important clinicians studying SG in Poland are Prof. Sergiusz Joźwiak, one of the discoverers of the TSC1 gene, and Prof. Katarzyna Kotulska-Jóźwiak (Children's Memorial Health Institute). For many years they have been not only successfully taking care of TSC patients, but also working on better clinical protocols and engaging scientists from all over Poland in applied and basic research on TSC. Among the centers closely collaborating with them is the International Institute of Molecular and Cell Biology in Warsaw. Scientists from the Laboratory of Molecular and Cellular Neurobiology, have participated in international and national research consortia, coordinated by Prof. Jóźwiak, aimed at defining new biomarkers to improve diagnostics and treatment (Epistop and Epimarker). At the same time, new preclinical models, both cellular (e.g., based on cells donated by patients and their families) and animal (e.g., zebrafish), are created and characterized in the laboratory to analyze molecular processes disrupted in TSC as well as to identify new drug targets. These studies have been and are funded by sources such as the EU Framework Programs (Epistop, Fishmed), the National Center for Research and Development (Epimarker), or the National Science Centre (OPUS, Sonata, Etiuda and Maestro grants) and have led to the identification of molecular processes disrupted in TSC that may represent complementary therapeutic targets in addition to mTOR protein.

TSC can have many different manifestations. It is often a huge trauma not only for patients, also due to social reactions, but also for their families. Let's be in solidarity with people with TSC and their caregivers! Advances in science and medicine, better treatment, proper care and public awareness of the real problems of this group, can contribute to a significant improvement in their lives.

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EPISTOP results summarized in animation movie


neurons microscopy photo with text May 15 TSC Global Awareness Day