Dr. Thiele and a patient

Founded in 2005 with an initial gift from the Herscot family, the Herscot Center for Tuberous Sclerosis Complex (TSC) received a second generous gift of $17.5 million from the family in 2015. The gift has allowed the Center to build on its existing solid infrastructure and expand its emphasis on collaboration between specialties, including neurology and psychiatry. Now forty-one specialists strong, the Center provides comprehensive care for over 400 patients with this complex genetic condition that affects many organ systems, from the brain, the most significantly affected system, to the skin, eyes, heart, kidneys and lung.

“The Herscot Center and Mass General have become a beacon for people with TSC and their families because they realize the knowledge and experience with the disorder is so high here,” says Dr. Elizabeth Thiele, a neurologist at Mass General and Director of the Center.

That beacon has attracted patients in large numbers from around the world. As a result, Thiele and her colleagues see patients of all ages, from unborn babies to octogenarians, with all manner of symptoms. The Center’s large patient population has allowed Thiele and her team to begin to recognize patterns in this disease, making connections that would not be possible in a clinic serving smaller numbers or a limited group, such as children only. These patterns have led to the recognition that TSC patients often suffer from neuropsychiatric disorders and need comprehensive mental health care, from psychiatric care to neuropsychological assessment to help for patients and families as they navigate social services.

The Center strikes a balance between treating each patient as an individual with unique needs and seeing the population as a whole that can inform care for everyone with the condition. “I think it can be looked at as a model for how we optimize care for people with complicated multi-system disorders,” says Thiele.

Tuberous sclerosis complex results from mutations in one of two genes, TSC1 and TSC2. The genes are involved in a cellular signaling pathway that regulates cell division. Often when this pathway is altered, the result is malignant cancer, but in TSC, the result is generally benign tumors, called tubers in the brain or hamartoma elsewhere, that crop up across many organs in the body. Because the disease affects a range of organ systems and appear in varying numbers over time, some patients are high functioning and may grow to adulthood without knowing they have the disorder while others may be severely compromised, to the point of being non-verbal or developing severe epilepsy at a very young age.

“Many describe living with TSC as walking a minefield,” says Thiele. “You can control seizures and then, bang! You have an issue with your kidneys.”

Thiele has been treating TSC patients for almost two decades. She began working with children, but then moved to Mass General fifteen years ago because she recognized that TSC patients needed continuity of care as they matured into adulthood. By working with patients of all ages, she began to develop insights, including new ideas about mental health.

For instance, she noticed that many of her patients suffered from anxiety, and that their feelings were not a result of coping with their disease but rather a symptom of it. This psychiatric diagnosis was being missed and patients were suffering from a lack of treatment.

This recognition was the first step of many that have led to new approaches to the psychiatric care of patients with TSC. One key insight is that patients with TSC can benefit from the same psychiatric treatments that work for people without the condition. “It is very difficult to find child psychiatrists in general, but for patients with TSC, many psychiatrists are reluctant to initiate treatment,” says Dr. Lawrence Selter, a child psychiatrist at Mass General and specialist at the Herscot Center. “The beauty of the Herscot Center is that we have a range of specialists with expertise in working with patients with this disorder.”

The Herscot Center’s list of mental health specialists includes experts in psychiatry and psychology to work up diagnoses and treatment plans and social workers to patients and their families navigate the social services they need. “Dr. Thiele has been the major teacher in helping me learn about TSC and the presence of psychiatric disorders,” says Selter. “She’s a neurologist, but she has an enormous knowledge of the psychiatric symptoms in her patients.”

Thiele pays attention to her patients, and that approach has led to other insights about the disease. For instance, while TSC patients often have benign growths, some develop conditions such as renal cell carcinoma and pancreatic neuroendocrine tumors. In TSC, these conditions can occur as early as four years of age, while in the general population they don’t occur until the 60s or 70s.

The Herscot team has begun to mine their large database of patient information looking for more patterns. Selter is interested in determining if anxiety is more prevalent among TSC patients and if symptoms differ from those experienced by the general population. Research collaboration has also begun with the Martinos Center for Biomedical Imaging at Mass General to begin to characterize mental health conditions in TSC patients.

“We’re trying to understand it,” says Thiele. “If you look at the brains of TSC patients, the anatomy of each is different. They have tubers in different areas and differing numbers. We’re working really hard to understand what are the diagnoses and what are the effective treatments.”

In addition to clinical work, Thiele also collaborates with several labs at Mass General researching TSC.  Thiele and Ramesh Vijaya, PhD, associate geneticist at Mass General, are working together to better understand the “second hit” involved in TSC affected organs, and to understand the relationship between chordoma and TSC.  Over the past several years they have also collected DNA and established cell lines on over 150 TSC patients.  Ramesh uses these samples to try to identify modifier genes in TSC which lead to autism.

Thiele and her team also work with Xandra Breakefield, PhD, professor of neurology, to develop gene therapy trials for TSC.  Breakefield’s lab has now constructed both TSC1 and TSC2 vectors.

In addition to these labs, the TSC clinical program obtains tissue from surgical procedures their TSC patients have undergone—including epilepsy surgery, SEGA resections (brain tumor), kidney resections, skin resections—and share them with several basic science labs, leading to important TSC findings, including a novel type of renal cell carcinoma in TSC and the identification of several mosaic mutations (with David Kwiatkowski, MD, PhD, at Brigham & Women’s Hospital).

For more information about the Herscot Center for Tuberous Sclerosis Complex, please visit our website.