DPD Deficiency foundation focuses on creating awareness, finding a cure, supporting families affected, and developing screening techniques. On this community outreach page, we discuss progress in finding a cure, talk about fund raising status and support individuals affected. We have explained some of this in the past. But we believe it is time to create a DPD Deficiency FAQ.
1. Dihyro pyrimidin
e dehdrogenase Deficiency. Its an enzyme deficiency. This enzyme help process Uracil & Thymine (pyrimidine bases of RNA and DNA respectively) and create end products of B-Alanine and Beta Amino Isobutyric acid.
2. Why do DPD Deficient have fatal reaction to 5-FU ?
5 FU treatment regimen depends upon DPD enzyme to process the 5-FU after it kills cancer cells. Lack of DPD makes the 5FU lethal and more often than not, causes the DPD Deficient to die.
500,000 people receive 5-FU treatment an year. Anywhere from 1% to 8% people have DPD Deficiency (depending upon which study you believe). This kills a lot of people each year.
2. b Children ? Many children with DPD Deficiency suffer from acute motor issues, intellectual formation issues, epilepsy as well as growth issues. Death for children affected with DPD Deficiency in early age is not rare.
3. What is relevance of Beta Alanine and Beta Amino Isobutyric Acid ? Beta Alanine helps control muscle formation and function. Beta Amino Isobutyric acid is a neuro inhibitor. Lack of the latter, can cause neurosignals from brain to malfunction.
4. What about Uracil ? Excess uracil is a neuro toxin. Negative impacts of this is still being studied.
5. What is ERT ? Enzyme replacement therapy. In this method of treatment, you are supplying your body with the enzyme that is missing.
6. What is a recombinant enzyme ? Recombinant enzymes are enzymes that behave identical to the enzyme to which its made for, but has a slightly different chemical formula. If your body is likely to kill the enzyme in its original fashion, this recombinant enzyme is more likely to survive as the variation acts as a "camouflage" and actually help your body.
7. Recombinant DPD enzyme has been created before. Why not have a therapy yet ? Porcine (from pigs) enzyme as well as human enzyme has been expressed before. Stabilization of this enzyme requires in many of the expressions, large quantities of reagents that are detrimental to human cell. b) More importantly, the enzyme molecule is fairly large and may not cross blood-brain barrier. We need significant research in figuring out how to have the effects of the enzyme reach the brain, as well as understanding its impact on rest of the body.
8. What about the mice model ? Phenogenomics institute in Toronto has created DPD Deficient mince (knockout ) using vectors made available from UC Davis. Some studies have completed and more are on the way to understand how these mice behave compared to general population and how they respond to challenges from 5-FU as well as recombinant enzyme.
9. When will a therapy be available ? We do not know yet.
10. What can we do to help expedite research ? Volunteer in IPS study. Mayo clinic is running a study using IPS cells. (stem cells created from your tissue. Not embyronic stem cells). They are looking for parental, sibling, and patient muscle samples to develop accurate models. Please participate. Foundation has awarded grants to reimburse for travel , room and board expenses to patients participating in such studies at Mayo. Spread the news. More scientists who are interested in this, more chances we will find a cure.
