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July 29, 2015 – Three new Cooley’s Anemia Foundation Medical Research Fellowships have been awarded for the 2015-2016 grant cycle. Combined with the three Fellowships which have been renewed from the previous cycle, the total amount of research funding for the current cycle comes to $195,000.
The recipients were selected by members of the CAF Scientific Review Committee, who evaluate applications on the basis of scientific content, the academic accomplishments and future promise of the investigator, the quality of the mentor and the relevance of the project to the understanding and treatment of thalassemia. The Committee made its recommendations for funding to the CAF Board of Directors, who approved those recommendations at its annual Board meeting.
First Year Recipients
The following individuals have been awarded new Fellowships for this grant cycle. Fellowships are awarded for one year with renewal for a second year contingent upon review of progress.
Daniel E Bauer, MD, PhD of Boston Children’s Hospital and Dana-Farber Cancer Institute, is investigating how genome editing may be useful in creating greater expression of fetal hemoglobin in adult thalassemia patients. His project is entitled “Genome Editing of Beta-Globin Gene Cluster Repressive Elements for Beta-Thalassemia.”
“All the clinical problems of thalassemia can be traced back to the sequence and regulation of the globin genes,” explains Dr. Bauer. “So there would seem to be a great opportunity to rationally counteract this underlying discrete molecular problem, if only we had enough knowledge and tools. Over the past few years there has been an unprecedented explosion in our understanding of various areas of basic science, including in human genetics, gene regulation, and genome editing. Together these advances make curative treatments for genetic disorders like thalassemia increasingly realistic.”
Emily Kreger, MD, University of California at San Francisco, has been awarded a fellowship for her project, “Early treatment of alpha thalassemia with intra-placental in utero hematopoietic stem cell transplantation.” Alpha thalassemia major is a serious condition which begins during the fetal stage and in which all four of the alpha globin genes are affected; it is sometimes known as fetal hydrops. Without treatment, patients with this form of thalassemia typically die before or shortly after birth. Dr. Kreger’s study will use animal models to gain information about the possible use of stem cell transplantation in the fetal stage as a possible future curative approach.
“As a Surgery Resident spending my research years with a concentration in Fetal Surgery, I have the privilege of working with a team at UCSF with the experience to develop an in utero intervention that compliments the current therapy for alpha thalassemia major,” Dr Kreger states. “My research is focused on alpha thalassemia major because, as a rare disease that is fatal without intervention, I believe we have the knowledge and tools to improve upon available therapeutic options to make a significant positive impact in these patients’ lives. The basic science work that I am doing will lay the foundation to bring a unique surgical approach to the treatment of a congenital medical disease, and strengthen the culture of interdisciplinary patient care.
“I would like people who have thalassemia and their families to know that if we are successful, my research will translate directly to improvements in patient care; our ultimate goal is an in utero cure for alpha thalassemia major. Reaching that goal would mean that babies diagnosed with alpha thalassemia major would require no further treatment after birth, a profound difference from the therapy that is currently available, and a true sea change in the quality of life for the patients and their families.”
Sant-Rayn Pasricha, MPH, PhD, FRACP, FRCPA, of the University of Oxford, is investigating “Epigentic therapies for thalassemic iron overload” for his Fellowship. Dr. Pasricha will be looking into issues surrounding hepcidin, a hormone which plays a significant role in iron regulation.
“Patients with thalassemia can experience a complex set of lifelong problems relating to anemia and iron overload,” says Dr. Pasricha. “My goal is to discover improved treatments which could enhance quality of life and wellbeing for these patients. We are exploring how genes which relate to iron overloading are controlled in patients with thalassemia, with a view to discovering new treatments which one day could improve the handling of iron and hence control or even prevent iron overload.”
The following have been approved for a second year of funding for their Fellowships.
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.”
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.”
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.
CAF congratulates all of our Fellows and looks forward to the contributions they will make to thalassemia both now and in the future.