TPI Df is a devastating untreatable childhood enzymopathy. Children are typically diagnosed within their first few years of life, experience anemia, recurrent infections, locomotor impairment and irreversible brain damage resulting in death within 2-6 years. As this is an extremely rare disease pharmaceutical companies are not pursuing treatments and academic research must cure this disease. All described pathogenic mutations preserve activity and pathogenesis results from reduced protein stability. Thus, the cure for this disease will be compounds that stabilize mutant TPI protein or slow its degradation. Furthermore, we’ve developed a human cellular model of TPI Df amenable to high-throughput optical screening and propose to screen FDA-approved compounds for a TPI Df cure. Similar methodology will be used to screen a diversity compound set, if needed.
Save JT Borofka & Others like Him
Born in Salinas CA, JT was diagnosed with TPI Df at the age of 9 months. Although the prognosis of the disease is extremely poor, JT was immediately put on a diet developed specifically to slow disease progression. This is not a cure but hopefully this will allow us time to identify a pharmaceutical cure for this disease before irreversible cognitive damage robs this child of life and happiness. JT desperately needs your help as do Esmerelda, Hanah, Lucas, Zaïna, Thomas, Daniel, Ashley, Wyatt and others in this country and all over the world.
Project: CURE TPI Deficiency
Researchers in the Department of Pharmacology & Chemical Biology working together with Dr. Andreas Vogt of the UPitt Drug Discovery Institute and Department of Computational and Systems Biology, we’ve validated our optical drug screening approach. The screen utilizes stable human cells expressing GFP-tagged mutant TPI bearing the “common” mutation that affects JT and others. Importantly, we’ve identified a positive control that increases mutant protein 250%. Although this compound itself is not a viable drug, it can be used in an unbiased drug screen. We propose to further develop the screen and implement it using a compound library composed of already FDA-approved drugs. Thus, a positive hit could more readily be used on patients as dosage and safety have been established. Furthermore, we can directly test compounds in TPI Df patient cells with the “common” mutation to validate their efficacy. We are looking for $37,000 to initiate a novel compound screen in the hopes of identifying a cure for JT and others like him.
$19,900 PT technical assistance
$9,600 Reagents, disposables, antibodies, media
$7,500 Chemical libraries