CAF’s $300,000 Medical Research Funding Moves Field Forward


August 25, 2014 – New explorations in gene editing. Connections between thyroid hormones and hemoglobin. Efficiency and safety in gene therapy. Using a protein to control iron. These are the ideas behind the four exciting new studies being funded by the Cooley’s Anemia Foundation this year.

These new fellowships join four renewed fellowships and a renewed clinical research grant to partake in a grand total of $300,000 in medical research funding from the Foundation.  CAF continues to move the field forward in a meaningful way with its substantail funding for 2014-2015.

So what’s going on in these new fellowship projects?

Gene editing.

shanrun-sm

Dr. Shanrun Liu

Shanrun Liu, PhD, of the University of Alabama at Birmingham, is using a new mouse model of thalassemia to test gene editing in his study, “Correction of Humanized Cooley’s Anemia Mice by Gene Editing of Hematopoietic Stem Cells.” The new mouse model, combined with a special gene editing technology, may produce results that can provide new information.

“Thalassemias are among the most common genetic disorders worldwide,” says Dr. Liu, explaining that past research in thalassemia has been valuable in understanding genetics, gene regulation and iron regulation. “The techniques to cure thalassemias will not only save millions of people who suffer from them, but can also be applied to many other blood disorders, such as sickle cell anemia.”

Thyroid hormones and hemoglobin.

Dr. David Wiley

David Wiley, PhD of Boston Children’s Hospital and Howard Hughes Medical Institute, is identifying drugs that affect thyroid hormones that can aid in increasing fetal hemoglobin production in his project, “The Role of Thyroid Hormone Signaling Pathway in Globin Switching.” If the amount of fetal hemoglobin can be increase in a person with thalassemia, it may mean that s/he will need fewer transfusions.

“I’m studying thalassemia for a few reasons,” Dr Wiley says. “As you know, many patients with thalassemia have debilitating symptoms and have a severely decreased quality of life.  Relative to other disease areas, such as cancer, the mutations that cause thalassemia are straightforward and it is clear that the disease can be effectively treated with small molecules that effectively regulate the globin switching process. My personal and professional goal is to find treatments for diseases starting with the most ‘targetable’ genetic diseases, and I personally believe that treatments for this disease are beckoning for discovery.”

Efficiency and safety in gene therapy.

Dr. Santhosh Verghese

Dr. Santhosh Verghese

Santhosh Verghese, PhD, of University of Oregon Health Sciences University, is exploring ways to improve the efficiency and safety of gene therapy strategies in his study, “Development of a 2nd Generation Mitotically-stable Anchored Non-Integrating Lentiviral Vector (aniLV-II) for Hematopoietic Stem Cell Gene Therapy.” Improving safety and efficiency of components of the gene therapy process can help to speed the development of effective therapies.

Dr. Verghese explains that one way of putting corrected DNA into a patient’s stem cell chromosomes is by using what is called a lentiviral vector; the challenge is to make sure the vector doesn’t also go anyplace other than the desired stem cell chromosomes.  He will be a new vector which he believes will be able to do this job more effectively. “With the support from CAF, we want to take this aniLV vector into next level that is by getting rid of the remaining viral vector DNA and retain only the corrected gene within the cells after gene delivery,” he says. “It is exciting to imagine this proposed vector as a space launch system at molecular level for safely delivering genetic cargo deep within the nuclear space where the therapeutic DNA get detached from the vector and establish within the nucleus.”

Using a protein to control iron.

Dr. Delphine Meynard

Delphine Meynard, PhD, of INSERM in France, explores ways to inhibit an enzyme that affects iron regulation in people with thalassemia intermedia in a study entitled “Matripase-2; new therapy for non-transfusion dependent thalassemia based on matripase-2 inhibition.”

Hepcidin is a protein that plays a big role in the iron levels in the body, so finding a way to increase or decrease hepcidin can have an effect on those iron levels; inhibiting the enzyme matripase-2 may regulate hepcidin. Dr. Meynard will examine compounds that could potentially play a role in this regulation, with the long term goal of identifying those that may eventually be safely used in treating iron overload.

“The goal of my study is to develop an alternative and potentially safer therapeutic strategy based on matriptase-2 inhibition,” says Dr. Meynard. “I intend to develop small molecules that will specifically block matriptase-2 activity in order to correct iron overload and improve inefficient erythropoiesis associated with non-transfusion-dependent-thalassemia.”

Continuing projects.

To learn about the projects which were funded by CAF last year and which have received renewed funding for a second year, please click on the links below.

Clinical research grant

Marsha Treadwell, “Self-efficacy and adherence with iron chelation therapies in thalassemia”

 

Medical research fellowships

Farzana Sayani, “Metabolomics biomarker profiles to predict cardiac disease in transfusion-dependent beta-thalassemia”

Hemant Kini, “Mechanism of PABPC4 action regulating terminal erythroid differentiation”

Carla Casu, “Novel approaches to treat iron overload in thalassemia”

Shigeki Iwase, “Variable number tandem repeats and heterochromatin in α-thalassemia”

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