At the 2014 Joint ACTRIMS-ECTRIMS Meeting in Boston (September 10-13, 2014), the GMSI Award (Grant for Multiple Sclerosis Innovation) was presented to the winners for the second time. The goal of the award is to promote research and support promising translational research projects that help to better understand and ultimately treat multiple sclerosis.
(lg) As with the first award ceremony at ECTRIMS 2013 in Copenhagen, the award was presented for the second time to the research projects with the most promising goals. The prize is worth a total of 1 million euros, which was distributed among the five winners. One indication of the great need for MS research funding is the rush of applications that Merck Serono has seen. Compared to the first award ceremony, the number of applications submitted more than doubled to a total of 205.
Promote key areas of research
The funding is intended to benefit projects conducting MS research in key areas of the disease. These include pathogenesis and identification of MS subtypes as well as response rates, meaningful disease markers, new potential treatment options and innovative patient support programs. Here, for example, new technologies such as mobile or e-health can be helpful in day-to-day patient management.
Of the more than 200 applications, eight research groups were invited to present their projects based on the criteria of innovative MS research (1), sound scientific rationale (2), feasibility (3), and practicality (4). Five applicants were allowed to receive the prize this time.
Repair of myelin by manipulation of microglial cells?
The first winners are PD Maria Domercq and Prof. Carlos Matute from the Achucarro Basque Center for Neuroscience and the Department of Neurosciences at the Universidad del País Vasco in Spain. Their research hypothesis addresses whether central nervous system (CNS) immune cells, microglial cells, have an indirect effect on myelin repair. The research findings could lead to the development of new MS treatment options.
When injury or infection is detected in the CNS, the release of ATP leads to the activation and proliferation of microglial cells, which accumulate at the site of lesions and eliminate damaged cells and cellular substances here by phagocytosis. However, excessive and sustained activation of microglial cells can also be harmful.
Existing data show that differentiation of microglial cells into M2 cells can positively influence tissue degeneration. In this context, the depletion of microglial cells need not always be necessary in MS therapy, but may even produce more effective therapeutic options by altering activation. The study the awardees applied for investigates whether microglial cell transformation can be altered by manipulating P2X4 receptors to cause the cells to lose their pro-inflammatory M1 functions and instead enhance their M2 properties, phagocytosis and regeneration.
Imaging biomarker for early detection of neurodegeneration.
PD Bruno Stankoff, professor of neurology at Pierre and Marie Curie University in Paris (UPMC), received his grant for a project looking at the utility of positron emission tomography (PET) in combination with [18F]-flumazenil in the early detection of MS. The aim of the study is to develop an index for neurogeneration. This is intended as an imaging biomarker to reveal neuronal damage at an early stage of the disease, either in relapsing or primary progressive MS. Another aspect of the research project is to discuss the role of brain gray matter in the disease.
Regulatory T cells
A project by PD Margarita Dominguez-Villar, Yale School of Medicine, is looking at whether MS patients have altered immune systems and whether this is related to regulatory T cell (Treg) function. These normally help to contain the immune response and thus prevent autoimmune disease. The results of the research could help develop new therapies to restore the ability to inhibit inflammation.
Specifically, the research focus is on what the mechanisms are in the generation of Th1 Tregs, how these cells function in vivo and in vitro , and exactly what the difference is between healthy people and MS patients. The PI3K/AKT/FoxO pathway in the differentiation of Th1 Tregs appears to play a role here, according to Dominguez-Villar.
Testing of BAFF and APRIL signaling molecules.
Another research project from the USA is also receiving financial support: PD Robert Axtell of the Oklahoma Medical Research Foundation is investigating the role of “B-cell activating factor” (BAFF) and “a proliferation inducing ligand” (APRIL) in neuroinflammatory disorders. BAFF and APRIL are signaling molecules that will be tested in two different animal models. One simulates MS, the other neuromyelitis optica (NMO). To investigate whether inhibition of BAFF and APRIL ameliorates or worsens disease in the respective animal models. The basis of the research idea is the knowledge that in autoimmunity the function of B cells is important. In this context, whether B cells, BAFF, and APRIL are pro-inflammatory or anti-inflammatory depends on the context of the autoimmune disease.
Myelin repair using nanotherapy?
PD Su Metcalfe, senior scientist at the John van Geest Centre for Brain Repair at the University of Cambridge, also beat out other projects with her research idea. She is investigating the extent to which nanotherapy with “leukaemia inhibitory factor” (LIF) can promote self-tolerance and myelin repair in MS patients. LIF is a stem cell cytokine.
Metcalfe formulated several questions that the research team set out to answer: does LIF nanotherapy protect against relapsing-remitting experimental autoimmune encephalomyelitis, other autoimmune diseases, and/or secondary progressive forms of neurodegenerative diseases? Does LIF nanotherapy increase the therapeutic benefit of antibody-mediated lymphodepletion? These and other questions will be answered with the help of the money distributed by the GMSI award.
Source: GMSI Award Ceremony, Joint ACTRIMS-ECTRIMS Meeting 2014, Boston.
InFo NEUROLOGY & PSYCHIATRY 2015; 13(1): 28-29.
