Evidence has linked autism condition with underlying dysfunction in the cerebral regions of the brain. However, the details surrounding the condition have, up until now, always been unclear.
The present study, conducted by researchers based in the Boston Children’s Hospital, used advanced stem cell technology to recreate cerebral cells which are identified by Purkinje cells from patients diagnosed with tuberous sclerosis complex (TSC).
TSC is a genetic syndrome that includes features similar to autism. During subsequent lab tests, cells showed unique characteristics which are helpful in explaining how autism condition develops at the molecular level.
The research team was led by Dr. Mustafa Sahin, director, and MD of the Translational Research Center at the Boston Children’s Hospital.
To recreate cells, Sandberg created induced potent stem cells using the skin or blood cells of the patients. The cells were further differentiated into neural progenitor cells which were later recreated into Purkinje Cells.
The team compared these cells which were created using patient’s blood with those of healthy people. Sahin comments, “We saw changes. The cells were seen to be bigger and to fire less in comparison to other control cells, exactly the way we have seen in the earlier models involving mice.”
TSC genetic defects are much harder to differentiate than the neural progenitor cells which indirectly suggests that TSC cells may impair the early developmental ability of the cerebral tissues. On further examination, Purkinje cells derived from the patients showcased traces of structural abnormalities while observing signs of the impaired developmental synapse.
A Platform to Uncover Autism Traits
The study is believed to be the first in creating human Purkinje Cells using an inpatient’s stem cells. Further, the team led by Sahin hopes to generate greater numbers of derived cells from inpatients in order to conduct an in-depth investigation to understand the differences between standalone TSC patients and those who have a history of autism condition.
Additionally, the team hopes to use the Purkinje cell platform to further study other autism-related genetic conditions such as SHANK3 mutations and Fragile X with an aim to test potentially viable drugs.
Sandberg explains, “Looking at changes, even if they are not major ones, is a critical part of the study. For instance, we now understand in TSC, mutations cause different effects even in different cell types.”
Further, TSC Purkinje cells also showed over-activations of cell growth pathways which are commonly referred to as mTOR. Nevertheless, the team treated the underlying affected cells with rapamycin, an mTOR inhibitor which is clinically used in TSC to effectively reduce tumors and related seizures.