Treatments for Pediatric Hemoglobinopathies
Gene based therapies to restore normal hemoglobin production and function in patients with hereditary anemia
Hemoglobinopathies such as Sickle Cell disease and β thalassemia can result in an array of chronic symptoms that usually arise shortly after birth and persist throughout a patient’s life. Beyond the direct morbidity associated with chronic anemia and pain crises, the use of regular blood transfusions can lead to a host of other complications, including iron aggregation throughout the body that can produce serious complications of the heart and liver. More permanent treatments involving bone marrow transplants can reduce or eliminate the need for blood transfusions but come with their own possible complications including immune rejection of the transplant.
Dr. Christopher Lux has a strong clinical understanding and first-hand experience with pediatric hematology and oncology, with a special focus on sickle cell disease and β thalassemia and the gene mutations that cause them. The basis of Dr. Lux’s research is to develop more effective and permanent treatment options for patients with heritable anemia through targeted hematopoietic stem-cell reprogramming. The approach Dr. Lux’s research group employs involves restoring hemoglobin function through targeted gene editing with tools such as targeted endonucleases including TALENs and the CRISPR/Cas9 system. He has demonstrated success in producing targeted gene insertions and deletions that can increase expression of fetal hemoglobin, potentially ameliorating disease symptoms despite the continuing presence of the underlying mutations.
In his efforts to validate the efficacy of fetal hemoglobin as a therapeutic target, Dr. Lux has developed a range of endonucleases capable of targeting the fetal (γ) hemoglobin genes, which produce fetal hemoglobin but are silenced after birth. Dr. Lux has already demonstrated the efficacy of these techniques by modifying human stem cells, studying their hemoglobin production after gene editing, and using animal models to demonstrate that he is successfully editing a stem cell population.
The combination of late stage preclinical research and direct patient access place Dr. Lux in an excellent position to offer collaborative opportunities to partners interested in developing gene-based therapies for hemoglobinopathies. Diseases in this field have lifelong implications, and advances of the technology used by Dr. Lux could be applied to a broad range of patient groups.
Stage of Development
- Pre-clinical in vivo
- Pre-clinical in vitro
- Collaborative research and development opportunity
- Sponsored research agreement
- Consultation agreement
- Clinical trial
- Lux CT, Pattabhi S, Berger M, Nourigat C, Flowers DA, Negre O, et al., TALEN-mediated gene editing of HBG in human hematopoietic stem cells leads to therapeutic fetal hemoglobin induction. Molecular Therapy - Methods & Clinical Development 2019;12:175–83. doi:10.1016/j.omtm.2018.12.008.
- Pattabhi S, Lotti SN, Berger MP, Singh S, Lux CT, Jacoby K, et al. In vivo outcome of homology-directed repair at the HBB gene in HSC using alternative donor template delivery methods. Molecular Therapy - Nucleic Acids 2019. doi:10.1016/j.omtn.2019.05.025.
- Lux C T, Scharenberg AM. Therapeutic gene editing safety and specificity. Hematology/Oncology Clinics of North America. 2017; 31: 787–795.
- Lux CT, Yoder MC. Novel methods for determining hematopoietic stem and progenitor cell emergence in the murine yolk sac. Int J Dev Biol. 2010;54: 1003-9.
- Lux CT, Yoshimoto M, McGrath K, Conway SJ, Palis J, Yoder MC. All primitive and definitive hematopoietic progenitor cells emerging before E10 in the mouse embryo are products of the yolk sac. Blood. 2008; 111: 3435-8.
- Rhodes KE, Gekas C, Wang Y, Lux CT, Francis CS, Chan DN, Conway S, Orkin SH, Yoder MC, Mikkola HK. The emergence of hematopoietic stem cells is initiated in the placental vasculature in the absence of circulation. Cell Stem Cell. 2008; 2: 252-63.
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