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. 

fda ema

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


The Thalassaemia International Federation announced the initiation of an MSc Programme (Blended) in “Inherited Haemoglobin Disorders,” a joint educational endeavour undertaken by the University of Nicosia (UNic), Cyprus. This is a unique Programme addressing a very specific and special topic with its faculty including world-renowned international experts. It is recognised globally and is supported by the European Haematology Association and the International Society of Haematology.

This Programme leads to an MSc degree with specialisation in Haemoglobin Disorders, mainly Thalassaemia and Sickle Cell Disease (SCD). The Programme is directed to medical professionals. However, even though usually the best candidates are Specialist Paediatricians, Specialist Haematologists and Internal Medicine Specialists, other disciplines may also greatly benefit from the Programme; e.g Blood Transfusionists and specialised nurses who have at least one university degree.

More information: M.Sc. Programme's website


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


Orphanet, the reference portal for rare diseases and orphan drugs with partnerships in 40 countries, has published its annual activity report for the year 2015. It details the activities of Orphanet, while stressing the highlights of the past year, including updates of the Orphanet databases, tools and documents, improved transparency and traceability and upgraded international positioning.

More information: Orphanet Activity report [PDF], Orphanews