In April 2014 when the DBAF awarded Dr. Harvey Lodish $21,281, the intent was to fill a gap for a few months until Dr. Lodish received government money. Unfortunately, Dr. Lodish was notified that the Telemedicine & Advanced Technology Research Center program had been reorganized and discontinued due to lack of available funding from Congress, leaving him with no funds to continue this important research. Without these funds, research would have halted at a critical juncture where the Lodish group has identified a set of drugs that appear to work synergistically with steroids in stimulating erythropoiesis in mice. With the DOD program reorganized and funding stopped, this research was in jeopardy after one year of making significant progress. The DBAF, with help from DBA Canada, stepped in to provide the funding! An award of $95,000 was given for Dr. Harvey Lodish’s project entitled, High-throughput screening identifies many novel potential therapies for Diamond Blackfan Anemia. Dr. Lodish stated,

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The grant generously provided by the Diamond Blackfan Anemia Foundation and DBA Canada has enabled us to begin to test our compounds on a new mouse model of chronic anemia – to see whether they increase the levels of key red cell precursors and of red cells themselves. We’re also modifying our cell culture system – where human stem cells divide and eventually differentiate into normal red blood cells that have lost their nuclei – such that levels of key ribosomal proteins including rps19 are reduced; this will be another DBA “model system” that will enable us to test our compounds for their ability to increase red cell production prior to possible use in the clinic

With April’s gap funding, Dr. Lodish provided the following summary of his lab’s very exciting work.

High-throughput screening identifies many novel potential therapies for Diamond-Blackfan Anemia
Sherry Lee, Xiaofei Gao, Lingbo Zhang, Lina Prak, Shilpa Hattangadi, and Harvey Lodish
Whitehead Institute and Departments of Biology and Biological Engineering, Massachusetts Institute of Technology, Cambridge MA 02142

Many Diamond Blackfan Anemia (DBA) patients respond to treatment with the steroid prednisone with increases in red cells, but continuous use of this and other corticosteroids causes severe side effects. We need additional drugs to treat this disease, and one way of proceeding is to screen existing drugs and related chemicals for their ability to stimulate red cell production.

Supported by generous grants from the U S Department of Defense, we screened a collection of over 2000 tested and approved therapeutic compounds for those that can stimulate mouse red cell production in culture. We obtained over 40 potential “hits” and then rescreened all of them in a new human cell culture system we developed. Ten drugs approved for human use stimulated human red cell production in this system at a developmental stage that suggests they may be useful in treating DBA. We have been screening these drugs one-by-one for their ability to stimulate red cell production in mice that are “models” for DBA and other bone marrow failure disorders. Encouragingly, we have already shown that one such drug, in clinical use to treat certain lipid (fat) disorders, works in this system! As this and the other new molecules have minimal side effects, several of these compounds have the potential to treat the anemia associated with DBA.