COMPOUNDS SUITABLE FOR THE TREATMENT OF MYELOPROLIFERATIVE NEOPLASMS AS WELL AS METHODS FOR THE DIAGNOSIS/PROGNOSIS OF MYELOPROLIFERATIVE NEOPLASMS

摘要

The present findings point to mutant HSCs as the cause of BM neuroglial damage that compromises MSC survival and function, critically contributing to MPN pathogenesis. In this sense, the present invention shows that the niche damage triggered by the mutant HSC is essential for the development of a haematopoietic malignancy previously considered to be caused by the HSC alone. Targeting HSC niche-forming MSCs and their neural regulation paves the way to more efficient therapeutic strategies in MPN. For this purpose, the present invention shows that an efficient therapeutic strategy for the treatment of MPN lies on the administration of neuroprotective compounds, such as 4-methylcatechol, capable of protecting BM sympathetic nerve fibres. Additionally, another efficient therapeutic strategy is shown herein as the administration of selective β3-adrenergic agonists such as BRL37344 or Mirabegron, since this strategy will compensate for deficient sympathetic stimulation of nestin+ MSCs.

主权项

1. A β-3 adrenergic receptor agonist compound or a neuroprotective compound capable of protecting bone marrow sympathetic nerve fibers, for use in treating and/or preventing MPN (myeloprofilerative neoplasms).