The Cooley’s Anemia Foundation (CAF) announced that is accepting applications from individuals with thalassemia for the 2016 CAF-ApoPharma Distinguished Scholar Award. The CAF-ApoPharma Distinguished Scholar Award, which was established in 2014, is made possible through a grant from pharmaceutical manufacturer ApoPharma.

CAF will award up to two scholarships to a U.S. citizen(s) with a clinically significant form of thalassemia pursuing doctoral studies in biomedical sciences, including medicine, pharmacy, nursing and basic research. (Ph.D., M.D., D.D.S., Pharm.D., D.V.M, etc.) in the United States or abroad. Total annual funding available for the awards is $20,000. Students enrolled in a doctoral program for the fall of 2016 are eligible to apply. A clinically significant form of thalassemia would include alpha thalassemia major, beta thalassemia major, beta thalassemia intermedia, e beta thalassemia, hemoglobin H disease, or hemoglobin H disease-Constant Spring.

Applications must be received at CAF by September 30, 2016.

More information: CAF website

The European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA) have set up a new ‘cluster’ on patient engagement. The cluster will provide a forum to share experiences and best practices on the way the two agencies involve patients in development, evaluation and post-authorisation activities related to medicines. This is especially important for rare diseases who show a high level of engagement in providing real life experiences, expertise as well as contributing to scientific discussion. The increased interaction through the new cluster will allow EMA and FDA to exchange information on how they engage with and involve patients in their work and on priorities and goals to scale up future engagement with patients. The FDA and EMA currently collaborate effectively for making joint applicants for providing orphan designations.

More information: Press release, Terms of reference [PDF], Orphanews

Current clinical gene therapy trials for β-thalassaemia and sickle cell disease (SCD) rely on addition of a functional but reduced β-globin gene to the genome of haematopoietic stem and progenitors cells (HSPCs) of patients [↗]. Early results from the latest trial [↗] indicate that gene addition might be therapeutic even for severe forms of the disease, but concerns over safety and universal applicability remain, and alternative approaches are sought. Notably, individuals with elevated γ-globin levels (and thus hereditary persistence of fetal haemoglobin, HPFH) show extremely mild disease symptoms, spawning attempts to exploit the phenomenon by engineered activation of the endogenous γ-globin. Genome editing instead of gene addition might minimise the risk to patients and has therefore been taken up enthusiastically for preclinical studies [↗]. Using the technology to activate the endogenous γ-globin might moreover be applicable to all β-thalassaemia mutations and sickle cell disease alike.

Genome editing for therapeutic activation of γ-globin has recently seen two landmark papers advancing the field. In 2015, Canver et al. [↗] used genome editing with the CRISPR/Cas9 system to disrupt erythroid-specific expression of the γ-globin repressor BCL11A, achieving high levels of γ-globin in normal HSPCs in the process. A publication by Traxler et al. in Nature Medicine this August [↗] takes an alternative approach based on the same concept of sequence disruption, instead mimicking a naturally occurring HPFH mutation that introduces a 13-bp deletion in the γ-globin promoter [↗] (see mutation details in IthaGenes [↗]). Encouragingly, the study once again shows high levels of γ-globin induction and additionally demonstrates significant phenotypic correction of SCD HSPC-derived erythroid cells in culture. However, at the heart of high efficiencies in HSCPs in both studies are integrating lentiviral vectors for continued expression of the CRISPR/Cas9 elements; while this allows accumulation of correction events in culture, it also accumulates any unwanted (off-target) editing events and moreover also poses the same risk of insertional mutagenesis as gene-addition approaches. Although genome editing therefore still has some way to go towards clinical application for β-globinopathies, γ-globin induction appears to be one of the most promising paths to get there. 

Bio-Rad Laboratories, Inc. announced the release of the Bio-Rad Library of Variants - a compendium of HPLC cases. This Digital Library contains case reports of variants haemoglobin provided by a select group of reference centres belonging to the worldwide community of laboratories actively working on detection of sickle cell, thalassaemia and other haemoglobinopathies and aims to educate professionals with the experience and knowledge of the global health care community.

More information: Bio-Rad Library of Variants