Dihydropyrimidine Dehydrogenase Deficiency

1. Dihydropyrimidine Dehydrogenase Deficiency DPD Deficiency Foundation A chance of a life time!

2. What is DPD Deficiency? • DPD Deficiency is an inherited condition • People with DPD Deficiency cannot properly metabolize Uracil, an essential component of food • Uracil acts as a poison when too much is introduced into the bloodstream • People with DPD Deficiency cannot maintain proper Uracil balance • People with an acute DPD Deficiency condition see symptoms as early as childhood, others can go through life until a triggering event exposes the condition • (fact check?) The most commonly known triggering event in non acute cases is the treatment for cancer using a Uracil based drug which creates a catastrophic, often fatal condition.

3. Cheryl Britton – Martyr • -Cheryl Britton was diagnosed with Stage 2 Colon Cancer in April, 2007. She was 43 years old-Surgery was successful, test results determined that the cancer had not spread.-Adjutant chemotherapy was delayed for several months due to surgery errors and post-op infection.-Her first chemo treatment was administered on 16 December, 2007-She died 16 days later. DPD test results returned postmortem. She was "totally deficient".-No mention was ever made, nor was anything stated in her treatment handbook about DPD Deficiency. Her experience is relived everyday throughout the World. • http://dpd-deficiency.com/chemo/chemo.html

4. DPD Deficiency is a potentially fatal genetic illness • About 2,000-3000 people die each year in the US • Up to 24 million more go undiagnosed and are susceptible to fatal drug interaction • You never know if you are one till you have a fatal reaction to wart cream or skin/breast-cancer/colorectal cancer treatment • More than the number of Americans who die in • Airplane accidents • Pediatric TB • E-coli • What is holding back treatment for DPD Deficiency? • Pharmaceutical research favors solving problems that affect larger numbers of people

5. Story of Athena • 7 year old child with DPD deficiency – really smart girl who is big on monopoly, Uno and sing along • Started toe walking at the age of 4 • Wheel chair bound at age 6 • Cannot write, or perform basic tasks with her hand • Remembers all fun songs • Best pal of her 1st grade friends • - Mom, Don’t cry! • I will be better one day! • Took 3 years and hundreds of • Thousands of $s to diagnosis

6. What is the DPD Deficiency Foundation? We are a non-profit whose mission is to foster awareness of the disease, provide general information to support families, promote scientific collaboration and fund research in support of a cure. For those who are affected and do not know it • We will foster awareness of existing screening methods and promote research into improved methods For those who are affected today: • We will partner with the medical community to directly fund research in pursuit of a cure and or therapies to sustain the afflicted For families • We will provide a clearinghouse for information on the disease • Provide a forum and support group

7. This is a hopeful time • Breakthroughs in genetics and biochemistry allow us to understand the nature of the disease • DPD is an enzyme and Enzyme Replacement Therapies (ERT) are showing great promise • We are already engaged with qualified pharmaceutical research companies to generate a drug • What does pharmaceutical research cost ? • Scientist $100,000 / year • Lab environment and facilities $100,000 / year • What does the Foundation cost? • Board Member salaries - $0 • Website and communication costs – Donated by foundation members • www.facebook.com/dpddeficiency

8. Original Slides

9. What is Uracil ? A • One of the four Nucleobases in the nucleic acid of RNA • Difference between RNA and DNA – Thymine instead of Uracil • Flourine reacting with Uracil creates 5-Fluoro Uracil. • inhibits RNA replication enzymes. • Causes cancer cells to die. • Commonly used in many cancer treatments • skin, colorectal, breast • Used for treatment of warts

10. What is Dihydropyrimidinedehydrogenase (DPD)? B • A very vital enzyme – everyone produces it – helps pyrimidine degradation • Crucial in processing Uracil • Creates beta amino isobutyric acid and beta alanine. • Both help with proper neuro-functions • Also processes 5-fluorouracil – removes it from the system so that cancer cells are dead and rest of the body is left safe. • In some people, either the enzyme is not produced or is metabolized by liver and other organs

11. DPD Deficiency C • Genetically inherited disease • Both parents should be carriers • Reduced ability to process Uracil and Thymine • When administered with 5-FU or Xeloda, such patients most commonly die • Rarely people survive • 8% of the US population suffers from this disease • More common among middle eastern (Jewish ) descendents. • As high as 14% ?