Sandhoff results from a genetic mutation that reduces the body's supply of an enzyme, called hexosaminidase ("hex"), used by brain cells to metabolize excess fatty material called lipids. Onset is typically at six months in human infants. The accumulation of lipids in brain tissue destroys the brain cells instrumental in controlling and coordinating body movement and results in inexorable deterioration of the brain and spinal cord. Children suffering with Sandhoff rarely see their sixth birthday. Sandhoff mice are similarly affected. Tay-Sachs is predominant to Ashkenazi Jewish populations, while Sandhoff, a severe form of Tay-Sachs, is not limited to any ethnic group. Both diseases are marked with deficient Hex enzyme functioning and are among a known group of about 50 diseases rooted in the inability to metabolize lipids or other materials. While Sandhoff and Tay-Sachs are relatively rare, one person in 5,000 is affected by a disease that falls into a category of lysosomal storage diseases.
Currently there is no treatment for Sandhoff or Tay-Sachs. Given that the human stem cells used in this study-both human neural and embryonic stem cells-were safe and effective in so many mice, the researchers believe that their study may serve as a springboard for development into a clinical trial.
These diseases are part of a much more common group of diseases called "neurogenetic diseases". These findings contribute fundamental basic knowledge about stem cell biology that will help inform medical scientists in their quest for understanding diseases such as Parkinson's, Alzheimer's, ALS, and a host of other neurological diseases.