Table 1.
Challenges of Precision Medicine in SCD and GenoMed4All Approach to Address Them
| Issues Raised on Personalized Medicine for SCD | How Genomed4ALL Addresses Them |
|---|---|
| Can we identify prognostic groups in SCD | |
| Different types of SCD/co-inheritance of alpha thalassemia. | Inclusion criteria: SCD patients with all genotypes. Genetic analysis of HBB and HBA2 and HBA1 genes is standardized for full coverage of mutations. |
| Variation in Hb F levels. Mutations on HBF2, BCL11A, and HBS1L-MYB genes. Influence of other genetic factors (known or unknown). | A GWAS analysis will be performed on all patients in a standardized way and enriched by imputation. |
| Blood tests and biomarkers. | Parameters agreed in consensus will be collected at steady state for all patients in a standardized form. |
| Imaging | TCD and MRI results will be collected for the most recent evaluations. |
| Selection of different treatments in sickle cell disease | |
| Drugs promoting HbF synthesis. Hydroxyurea is started at an early age and as a standard of care for most patients, making it difficult to assess the effect on the evolution of the disease among different groups of patients all receiving this drug. | Use of hydroxyurea at the time of inclusion and total cumulative years of use. MCV and % of hemoglobin F in steady state are also registered. The GWAS analysis is expected to cover the presence of particular variants in the BCL11A, HMIP and HBC2 genes. The inclusion of metabolomics data will shed light on the effect of hydroxyurea on different patients. |
| New drugs with different targets (eg, Increasing hemoglobin levels, blocking abnormal red cell adhesion). | All participation in clinical trials regarding new drugs will be collected. |
| Drugs targeting abnormal erythropoiesis and bone marrow niche. Bone marrow aspirates are not performed routinely in SCD patients. |
IE by the assessment of soluble transferrin receptor, absolute reticulocyte count, and transfusion status (either occasional or regular) will be evaluated in all the patients. |
GWAS = genome-wide association study; HbF = hemoglobin F; IE = ineffective erythropoiesis; MCV = mean corpuscular volume; MRI = magnetic resonance imaging; SCD = sickle cell disease; TCD = transcranial Doppler.