At the semi-annual meeting of the Swiss Group for Clinical Cancer Research (SAKK), the 2014 SAKK/RTFCCR/Gateway Research Grant endowed with USD 450’000 was awarded to Prof. Dr. Radek Skoda, University Hospital Basel, and his research team for a research project aimed at creating a novel treatment option for bone marrow cancer patients without therapy alternatives.
The winning proposal was chosen out of 10 initial grant applications and stood out for its high potential for patient benefit, significance, innovation and feasibility. With no current cure available, MPN are a group of chronic leukemias (blood cancers) in which patients produce too many blood cells. These increased blood cell numbers cause problems to the patient such as bleedings or thrombosis and some patients may progress to acute leukemia, a life threatening condition.
Shawn Stephenson, President and Eveline Mumenthaler, Director of Rising Tide Foundation, along with Teresa Hall Bartels, President of Gateway for Cancer Research, awarded the winner, Prof. Dr. Radek Skoda from the University Hospital Basel, for his novel “Phase II study to test the effects of beta-3- sympathicomimetic agonists on the disease course and mutant allele burden in patients with myeloproliferative neoplasms”.
Most MPN patients (>80% overall) have a gene mutation called JAK2-V617F. The disease is maintained by mutant MPN stem cells that reside in the bone marrow in specialized locations called “niches”. These niches need connections to the nervous system. New findings show that these connections are destroyed by the presence of the mutated MPN stem cells. The research teams around the co-applicant Prof. Simon Mendez-Ferrer and Prof. Radek Skoda found that some drugs (beta3- sympathicomimetics) can restore these damaged niches and at the same time reduce the MPN disease manifestation in a mouse model of MPN.
Such sympathicomimetic drugs are already being used to treat patients with asthma or hyperactive bladder. These drugs have shown to have only few side effects. The research team is now to test the effects of the beta-3-sympathicomimetic drug Mirabegron (Betmiga®) on MPN disease in 36 patients that carry a JAK2-V617F mutation. Betmiga® is currently approved for the treatment of hyperactive bladder. The researchers expect that Mirabegron will have a beneficial effect on bone marrow niche cells and will thereby improve the disease manifestation in MPN patients.
This study should provide a rapid answer whether targeting the nervous system of the niche cells could be useful for patients with MPN and warrants to be tested in larger and more long-term studies. There is currently no cure for MPN. The approach proposed by Prof. Skoda and his team is novel and fundamentally different from the current strategies, since the primary target of therapy is the correction of the stem cell niche damage, rather than the malignant clone itself.
The current trial may create a novel treatment option with reasonable chance for clinical activity for these patients without alternative therapy option. As a joint front, Gateway, RTFCCR and SAKK decided in 2011 to create a strategic partnership with the aim to stimulate innovative and practice relevant oncology research that may lead to more potent, less toxic and potentially life-saving treatment options for cancer patients. The Call for Proposals was now conducted for the second time. All submitted proposals were reviewed by an international review committee comprising of Gateway, RTFCCR and SAKK scientists in a two-step procedure, with a final decision in May 2014