New research from CFRI and the Catalan Institute of Oncology in Spain sheds light on the cellular processes that underpin a disease that can cause developmental delay in children.


Tuberous sclerosis complex (TSC) is a rare, genetic disease where thick pale ridges known as tubers grow on the brain and other vital organs including the heart, kidneys, lungs, eyes, and skin. TSC symptoms for children and adults can also include intellectual disability, behaviour problems, seizures, skin abnormalities, and lung disease.


An estimated one in 6000 children are born with TSC.


This new research improves understanding of how tubers grow and could lead to the development of new therapies. It was published on March 6 in the Journal of Pathology.


“Our findings identify a new molecular pathway that is altered in TSC,” says Dr. Christopher Maxwell, a lead author on the study. “In the future, this pathway could be targeted by new drugs to complement the effects of existing drugs and better manage the disease.”


Researchers studied cells from tuber samples from patients with TSC. They found that the loss of a specific enzyme resulted in abnormal microtubules, part of the cell’s internal structure, and contributed to the growth of tubers. The enzyme is called Rho-associated coiled-coil containing kinase 2 (ROCK2) and is known to regulate the shape and movement of cells.


“We need to do more research to improve our understanding of how to restore this important molecular pathway and, potentially, slow or stop the progression of the disease,” says Dr. Maxwell.


These findings also support the hypothesis that the loss of a tumour suppressor gene, TSC2, can result in abnormal microtubule structures and affect the ability of cells to grow correctly.

Researchers in Barcelona collected tuber samples from nine patients with TSC who were undergoing surgery to remove or reduce tubers on their brains. The Spanish research team examined the samples and identified the new molecular pathway. The CFRI research team led by Dr. Maxwell studied the molecules in this pathway by creating new cellular models for TSC.

The study’s lead authors also include Pooja Mohan, CFRI; Dr. Isidre Ferrer, Bellvitge Institute for Biomedical Research; Dr. Maxwell, CFRI; and Dr. Miguel Angel Pujana, Catalan Institute of Oncology, Bellvitge Institute for Biomedical Research. At the time of the research, Pooja was a UBC CFRI masters student. She graduated in 2013.

For more information: 

Isidre Ferrer, Pooja Mohan, Helen Chen, Joan Castellsague, Laia Gómez-Baldó, Marga Carmona, Nadia García, Helena Aguilar, Jihong Jiang, Margaretha Skowron, Mark Nellist, Israel Ampuero, Antonio Russi, Conxi Lázaro, Christopher A Maxwell,  and Miguel Angel Pujana. Tubers from patients with Tuberous Sclerosis Complex are characterized by changes in microtubule biology through ROCK2 signalling in Journal of Pathology. Published online March 6, 2014. DOI: 10.1002/path.4343