The National Institute of Diabetes, and Digestive
and Kidney Diseases has funded our research on hereditary fructose intolerance
for over 23 years. The abstract for the most recent support can be viewed by
clicking here. The most recent work has three goals:
1) To define mutations responsible for hereditary fructose intolerance (HFI)
in the American population, especially in those ethnic groups not previously
studied. This is important because in order to diagnose a genetic disease using
the mutations that cause the disease one has to know what most of the
mutations are and how common each is. Otherwise, someone could have a HFI
mutation and it would not be detected because scientists are unaware of it.
Current standards require that a valid genetic test include a screen for 90% of
all mutations for a given disease. For HFI, we now know only ~80% of ALL
mutations and are able to routinely screen for those that comprise 75 –
95% but only among the Caucasian population. These same mutations comprise only 5-60%
of alleles in the African American, Asian American, and Hispanic population.
More research is needed.
2) To answer questions regarding the pathology and physiology of the fructose
normal metabolism and of the disease in an animal model. More understanding is
needed.
3) Past research determined the
problem with the enzyme that is at the root of HFI for 80% of those who suffer. Using this knowledge a chemical and
computational search for drug candidates is being done that will possibly
reverse the effects of the mutation.
4) Those who suffer from HFI
have revealed our lack of complete understanding of normal fructose metabolism. Research is being done using
bioinformatics and cell biology to define the physiological sites for fructose
metabolism.
The investigations will: 1) determine the variety and prevalence of the
mutations that cause this disease in America; 2) help to understand the
biochemical roots of HFI caused by specific mutations, including any that
affect expression of the aldolase gene, 3) provide insights into the structure
and mechanism of this important enzyme by finding drug candidates that change
its pathochemistry, and 4) establish an animal model in the mouse by gene-targeting
technology. Eventually this animal model will help us understand the pathophysiology
of the disease better and allow for trails of potential new treatments.
If you would like to become involved in our research, please email us at tolan@bu.edu.