A new therapeutic strategy for patients with myeloproliferative neoplasms
Researchers at the 'Stefano Ferrari' Centre for Regenerative Medicine at the University of Modena and Reggio Emilia (Unimore), coordinated by Professor Rossella Manfredini of the Department of Biomedical, Metabolic and Neural Science, have identified a new therapeutic strategy to inhibit bone marrow fibrosis in patients with primary myelofibrosis, a myeloproliferative neoplasm. The results of the AIRC-supported study are published in the international journal Leukemia of the Nature group.
Myelofibrosis is a cancer affecting blood stem cells for which there is no definitive cure. Myelofibrosis is characterised by the development of fibrous tissue in the bone marrow, which is the production site of all blood cells. As a result of fibrosis, the bone marrow progressively loses its function, putting patients' survival at risk.
A new strategy to inhibit fibrotic transformation of the bone marrow at an early stage comes from researchers at Unimore's 'Stefano Ferrari' Centre for Regenerative Medicine, thanks to the support of the AIRC Foundation for Cancer Research under the '5 per mille' programme entitled 'MYeloid NEoplasms Research Venture AIRC' (MYNERVA), coordinated by Alessandro Vannucchi of the University of Florence. MYNERVA focuses on myeloid neoplasms.
The results obtained by the group of Rossella Manfredini and colleagues, published in the journal Leukemia of the Nature group - one of the most important haematological journals internationally - showed that by targeting the osteopontin protein it is possible to interfere with the evolution of bone marrow fibrosis. Professor Rossella Manfredini is head of the Genomics and Transcriptomics programme at the “Stefano Ferrari” Centre for Regenerative Medicine at Unimore.
'Current therapies are not able to significantly interfere with the development of bone marrow fibrosis, which leads to a substantial worsening of the clinical condition and reduced survival of patients,' explains Professor Manfredini. 'The identification of new anti-fibrotic therapies therefore remains a priority in the treatment of the disease. For this study, we used in laboratory mice with myelofibrosis drugs already used in clinical trials with patients suffering from different types of tumours, in order to accelerate the transfer of results from the laboratory bench to the patients' bedside'.
'In a previous study,' adds research collaborator Professor Elisa Bianchi, 'we found that osteopontin, a molecule that promotes fibrosis, is significantly increased in the plasma of patients with myelofibrosis. In particular, the concentration is higher in patients with more severe bone marrow fibrosis and a worse prognosis. The results obtained had been published in the same journal in 2018. Based on these data, we then focused on identifying new therapeutic approaches aimed at inhibiting osteopontin activity.’
In the laboratory, we evaluated the effect of several drugs on cultured cells obtained from patients with myelofibrosis,' explains Dr Sebastiano Rontauroli. A very small number of drugs that proved effective on cultured cells were then evaluated in laboratory mice with myelofibrosis. In particular, the results showed a marked reduction in plasma osteopontin levels and bone marrow fibrosis in mice treated with a drug, ulixertinib, selected because it can effectively reduce osteopontin production in cultured cells and already used in clinical trials with patients for other forms of cancer.’
As further confirmation of the relevance of osteopontin as a possible new therapeutic target,' explains Dr. Lara Tavernari, 'we have also shown that inhibition of osteopontin activity - and not only of osteopontin production - by administering specific monoclonal antibodies directed against this protein results in a marked reduction of bone marrow fibrosis in mice with myelofibrosis.
Overall,' Professor Manfredini concludes, 'these data show that inhibition of ostepontine production or activity may represent a new therapeutic approach to interfere with the development of bone marrow fibrosis in patients with this disease and to develop more targeted and precise treatments. In fact, since the drugs we use are well tolerated in patients with other types of tumours, we are planning to develop a clinical trial to be started as soon as the necessary authorisations are obtained.’
‘This result of great scientific relevance and considerable application potential, achieved by Prof. Manfredini's group,’ concludes Prof. Michele Zoli, Director of the Department of Biomedical, Metabolic and Neural Science, ‘is a demonstration of the great scientific value of research groups led by professors in the department and the best recognition of the departmental policy for research development’.
Rossella Manfredini
She graduated in Biological Sciences from the University of Modena in 1988 with a mark of 110/110 with honours. In 1994, she obtained a PhD in Experimental Haematology and in 1996 her specialisation in Biochemistry and Clinical Chemistry. A recipient of AIRC and Lega Italiana Lotta contro i Tumori grants, she was a postdoctoral fellow at Temple University in Philadelphia (US), obtaining a US patent in 1998 for 'Use of AS c-fes and ATRA oligonucleotides in M3-type leukaemias'. She has been Full Professor of Applied Biology at Unimore since 2013.
She is author of 115 scientific publications in high-impact international journals. She has been working for more than 30 years on the biology of stem cells, both normal and pathological, with particular reference to the molecular mechanisms underlying the processes of self-renewal, proliferation and differentiation. Her main research topics are: the molecular and functional characterisation of normal and leukaemic haemopoietic stem cells, the study of clonal heterogeneity of the stem compartment in chronic myeloproliferative neoplasms, the identification of leukaemic stem cell subpopulations in chronic myeloproliferative neoplasms.
Unimore's “Stefano Ferrari” Centre for Regenerative Medicine (CMR) is a centre of excellence in international research on the characterisation of stem cells and their clinical application for cell and gene therapies. The centre is equipped with state-of-the-art equipment and houses a GMP (Good Manufacturing Practice) certified “cell factory”. The CMR is home to the Interdepartmental Centre for Stem Cells and Regenerative Medicine.
in the photo from the left: Dr. Lara Tavernari, Prof. Rossella Manfredini, Dr. Sebastiano Rontauroli and Prof. Elisa Bianchi
Categorie: International - english
Articolo pubblicato da: Ufficio Stampa Unimore - ufficiostampa@unimore.it il 22/03/2023