Dr Srini Kaveri, France
Dr Srini Kaveri is head of the Immunopathology and Therapeutic Immunointervention Laboratory at INSERM in Paris, France. He is an expert member of Committee of European Medicines Agency (EMEA) on the use of IGIV.
Research proposal: ‘A shift in regulatory T cell and Th17 T cell balance: an insight into a novel mechanism of action of IGIV (Gamunex®)’ (2 years).
Recent research in several experimental models has shown that there is a reciprocal relationship between T-reg and Th17 cells in which IL-6 plays a key role indicating whether the immune response is dominated by pathogenic Th17 cells or protective T-reg cells. T-regs have anti-inflammatory properties and can cause quiescence of autoimmune diseases. Shifting the balance away from Th17 with a concomitant expansion of functionally potent T-regs would constitute one of the plausible mechanisms through which IGIV exerts its tolerogenic potential.
Dr Kaveri and his co-investigators intend to examine this hypothesis using EAE model (an animal model for multiple sclerosis), wherein IGIV is already shown to be beneficial via expansion of T-reg population to protect the animals from the disease.
Dr Kaveri expects that his studies will reveal whether IGIV is able to exert its beneficial effect by modulating the balance between Th1, Th17 and T-reg cells. He believes that elucidating such cellular mechanisms will improve our understanding of effects of Gamunex on T cells and help better identify novel targets for IGIV therapy.
Dr Masanori Sasaki, USA
Dr. Sasaki is an Associate Research Scientist in Neurology at Yale University School of Medicine in New Haven, Connecticut.
Research proposal: ‘Combined intravenous immunoglobulin and cell therapy for spinal cord injury’ (2 years).
Spinal cord injury (SCI) in the US is estimated to effect more than 11,000 people each year. Most SCI results in permanent disability of motor and sensory function below the injury site. Much research into the repair of SCI is ongoing, including cell transplantation therapy however, there are still no accepted interventional therapies available.
Dr. Sasaki and Dr. Jeffery Kocsis (Co-Invesitgator, Professor of Neurology, Yale University School of Medicine) recently demonstrated that the transplantation of myelin-forming cells, such as olfactory ensheathing cells (OECs), into experimental SCI animals promotes functional recovery and has anti-apoptotic effects on motor neurons in brain. The use of intravenous immunoglobulin (IGIV) has been used in treating many immune-mediated neurological disorders, but little is known about the mechanism by which IGIV promotes functional recovery. One possibility is that IGIV can stimulate macrophage invasion into injured nervous tissue and enhance phagocytosis and the clearance of damaged myelin.
Dr. Sasaki and colleagues hypothesize that IGIV can stimulate clearance of the injured myelin and that subsequent cell transplantation will effectively contribute to the repair of the damaged neural tissue and this will be the focus for their study. Success would provide important preclinical data as a prelude to clinical studies for SCI and other types of neural trauma.
Dr Ingemar Merkies, The Netherlands
Dr Merkies is a neurologist at the Department of Neurology at Spaarne Hospital in Hoofddorp, The Netherlands. Furthermore, he works as a clinimetrician at the department of neurology of Erasmus medical centre, Rotterdam, and department of neurology of Maastricht university medical centre, Maastricht, The Netherlands. He is a committee member of the International Neuropathy Consortium.
Research proposal: ‘Peripheral Neuropathy Outcome Measures Standardisation (PeriNomS) Study’ (2 years).
In the past years, various methods have been used to study health outcomes in patients with treatable neurological conditions such as Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and monoclonal gammopathy related polyneuropathy. The applied outcome measures range from impairment measures to scales that assess daily activities and quality of life. Presently, therapeutic studies often use different scales, which hamper the comparability of results. Moreover, not all outcome measures have been assessed for ease of use, reproducibility, validity and responsiveness.
To overcome these important shortcomings, the Peripheral Neuropathy Outcome Measures Standardization (PeriNomS) study was designed. This study will compare various selected outcome measures to study the clinical applicability in these neuropathies. These measures have been selected by reviewing the literature and using the opinions of experts from all over the world in various workshops already performed. A total of 140 recently diagnosed patients will repeatedly be examined (using the same tests) to measure important clinical changes over a 12-month period. The ultimate goal is to construct a set of accurate and sensitive outcome measures making it possible to interpret and compare results between various clinical studies in these conditions. Additionally, this study provides the opportunity to examine, in close collaboration with patients, the clinical relevance of changes in their functional state after receiving treatment.