We identified a novel potential therapeutic target for diseases characterized by alterations in the number or function of platelets. Those include Essential Thrombocytemia (ET), a subgroup of myeloproliferative neoplasms (MPN) due to somatic mutations occurring at the level of hematopoietic stem cells, in particular those stem cells primed to become megakaryocytes (Mk), the cells from which platelets are generated. These mutations bring to chronic and uncontrolled platelet production, causing higher risk of developing thrombosis and leukemic transformation. Within the hematopoietic system, our gene is expressed in Mk-primed hematopoietic stem cells, in MK progenitors and in platelets. In its absence, platelets are generated with slower kinetics, they are more immature, and a higher fraction is degraded. In a MPN mouse model in which the gene we are studying is not present, the thrombocytemia typical of the disease does not occur.
Very little is known of the gene we are studying, which is a Tdark. We are not aware of competitors that are sconsidering it. A potential therapeutic target for diseases characterized by alterations in platelet quality, number, or function. The KO murine model has only platelet alterations; platelets are more immature but functional. In the MPN model due to the JAK2-V617F mutation, in the absence of the gene we are studying thrombocytosis, typical of the disease, does not occur. Therefore, a treatment that have this gene as target is expected to be non-toxic and highly specific for platelets. This is different compared to most available MPN treatments, which mainly act on disease symptoms but do not cure the disease. Novel drugs acting on the JAK/STAT pathway are available, but they are not platelet-specific, cause important side effects, and induce resistance over time.