Genetic, computational and pharmacological aspects of neurorehabilitation

Description

The Neurobiology, Computational Biology and Pharmacology research area is operating two labs in Bosisio Parini (Lombardy) and Padua (Veneto). Its research activity is mainly focused on rare neurological, neurodegenerative and developmental diseases; among these of particular importance are syndromic forms of mental retardation, autism and epilepsy as well as neuromuscular diseases. The group research is carried on in strict collaboration with the Medea Institute clinical departments.

In the case of syndromic cognitive disorders the study usually begins with rearrangements characterization through karyotype/Array CGH which is further refined through genetic and molecular analysis. In this field, the genetic characterization of the 22q13 terminal deletion, causing the Phelan-Mc Dermid syndrome, is well established among the group research subjects. Association studies between genomic polymorphisms and behavioral and emotional phenotypes are also performed in cohorts as well as families.

The research on neurodegenerative and neuromuscular diseases is focused on the molecular and genetic characterization of motor-neuron related diseases as Juvenile SLA and Spastic Paraplegia. The hypothesized pathogenetic mechanisms are tested through cellular or animal models. Specific Drosophila m. models have been developed in the Padua lab and are used to elucidate the neurodegenerative processes as well as to test compounds or conditions with potential therapeutic effects.

The use of narrow therapeutic index drugs often prescribed off label is among the critical aspects of developmental rehabilitation. The Pharmacology section is performing pharmacokinetics, pharmacogenetic and pharmacovigilance studies related to the therapies in use in the rehabilitation hospital allowing for an optimal utilization of a wide range of antipsychotic, antidepressant and antiepileptic drugs.

The Computational Biology lab is performing Population Genetic studies aimed at the identification of genomic variants (SNPs) which underwent natural selection during the human evolution and which therefore can be considered as functional. The a priori identification of functional variants, possibly connected to the pathology or to relevant phenotypic traits, can improve the pathogenetic mechanisms comprehension allowing for more effective diagnoses. The genomic variants are also studied from the functional point of view through computational approaches followed, when possible, by experimental validation. Furthermore, the models and software tools developed to this purpose find applications in High Throughput sequencing analyses which require the prioritization of hundreds of variants based on their computationally inferred functional role.

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