A team from Baylor College of Medicine has identified a new biological process underlying the Batten disease. The aim of the research was to understand the functioning of the lysosomes involved and to identify a possible lever for the therapies.
The disease is associated with a defect in the CLN8 protein located in the endoplasmic reticulum. Nevertheless, the Batten is one of the so-called lysosomal storage diseases. As a result, the researchers already imagined that the mutation was to be found in a protein, however, located in lysosomes. The study clarified some of the mechanism.
The researchers analyzed 4 proteins that help lysosomal enzymes exit the endoplasmic reticulum. Among these there was also CLN8, the only one that interacted with two thirds of the enzymes tested. As a result, scientists focused on it and switched to animal modeling.
Guinea pigs with a defective version of CLN8 had fewer enzymes in lysosomes. In fact, protein is necessary to allow newly formed enzymes to go out and do their job. CLN8 acts in practice as a cargo transporter, which selects and transfers the newly synthesized enzymes into the Golgi complex. Here they are modified and then sent to the lysosomes. In those who suffer from the Batten disease the process does not work.
When the protein does not work properly, the lysosomal enzyme can not cross the endoplasmic reticulum. As a result there is a deficit within the lysosomes, which leads to the development of the disease. It remains to be seen whether CLN8 works together with other proteins, how it responds to cell degradation and how it recognizes the enzymes to be transported. Furthermore, it will be essential to understand how to correct the process with drug therapy.