Experimental neuropathology
Experimental neuropathology
Our first attention is in the clinical neuropathology aspects of human peripheral nerves. We not only provide diagnostic to patients but we are providing the basis for many studies and collaborations around the world. One of the major contributions is in the appreciation of a neuropathic component in the pathogenesis of motor neuron diseases. We also contributed to the understanding of the different kind of axonal neuropathies and published many original papers in this field. In addition, we developed an interest in experimental animal models of neuropathies, especially in mouse. We directly provide morphological analysis of the murine nervous system after experimental manipulation. Other achievements are in the preclinical morphological validation of stem cells and gene therapy for Multiple Sclerosis and Metachromatic Leukodystrophy.
Next, although Amyotrophic Lateral Sclerosis has been considered as a disorder of the motor neuron cell body, recent evidences show the non-cell-autonomous pathogenic nature of the disease. Axonal degeneration, loss of peripheral axons and destruction of neuromuscular junction are early events in the disease pathogenic cascade, anticipating motor neuron degeneration and the onset of clinical symptoms. Taking advantage of the unique repository of human nerve biopsies available in our Unit, we showed that TDP-43 aggregation in the peripheral nervous system can serve as early Amyotrophic Lateral Sclerosis biomarker.
Research activity
Peripheral Nervous System involvement in Amyotrophic Lateral Sclerosis: from diagnosis to disease understanding. In this project we will define the role of Schwann cells in TDP-43-linked ALS toxicity of in vivo ALS models. Furthermore, we will determine non-cell autonomous effect of Schwann cells in a stem cell-based ALS model, using Organ-on-a-Chip technology.
Biomarkers in Amyotrophic Lateral Sclerosis.
Discovering of new biomarkers in ALS would facilitate diagnosis and thus might accelerate initiation of neuroprotective therapies. In this project we will develop novel ALS-specific biomarkers such as TDP-43 expression and localization in motor nerves, candidate protein-based biomarkers in the blood and/or cerebrospinal fluid of patients and imaging to define the earliest manifestations of ALS, improve their differential diagnosis and monitoring disease progression from pre-symptomatic to later stages of the disorder.
