In March of 2011, Kevin Eggan, Ph.D., an esteemed and leading researcher in motor neuron diseases and Associate Professor of Stem Cell and Regenerative Biology at Harvard University, received an award to research the mechanics of BVVL. This research is the first of its type into the investigation of BVVL. Dr. Eggan received the MacArthur Fellowship in 2006 and received the Presidential Early Career Award for Science and Engineering from President George Bush in 2008.


Thus far, the safest and most rapid method for developing a new therapy for a genetic disease has been to develop animal models that mimic the condition. These animal models allow many candidate therapeutics to be tested in parallel for their safety and effectiveness prior to their use in patients. The generation of an animal model of a disease, such as one for BVVL, requires first that the gene causing the disease has been identified and then second, that a similar mutation can be induced in the genome of a model animal, usually a mouse. In the case of BVVL, several mutant genes have now been discovered that appear to encode riboflavin transporters. These transporters act as important gateways into the body and into our cells. When they function normally, they carry this vital nutrient to important organs in the body including the nervous system. Studies thus far suggest a deficiency in the function of these transporters and perhaps an inability for riboflavin to reach the right parts of the body might be the cause of BVVL.

Researchers at Harvard in Dr. Kevin Eggan’s laboratory have spent the past year working towards the creation of a mouse model of the disease by “knocking out” the function of one of the genes known to carry mutations in individuals with BVVL. The goals of these experiments are to test whether mutations in these genes encoding transporters are sufficient to cause disease and identify if the mutant mice can serve as an accurate disease model.

The researchers were successful in generating mice that carry mutations in one of the BVVL candidate genes and are now carefully characterizing the impact that this mutation has on the animals. Surprisingly, initial results seem to suggest that the mutant animals that are predicted to lack all expression of the transporter are dying earlier than expected, even before birth. Currently, the investigators at Harvard are trying to understand the exact time of the loss of the animals that carry the candidate BVVL mutations. The goal of these efforts is to overcome this early loss and create a model that can more accurately reflect the disease, which often strikes during adolescence.

Creating a model that most accurately represents the human disease is essential. Testing a therapy, even a particular nutritional supplement related to riboflavin, in a population of affected mice is the first experiment that might lead to a human clinical trial in the future.

MARCH 2016:

Dr. Kevin Eggan’s research was published to Human Molecular Genetics. Click here to see the full article.