SSADH deficiency is a rare and debilitating neurometabolic disease. It is caused by mutations in the gene encoding for the succinic semialdehyde dehydrogenase (SSADH) enzyme, that lead to the synthesis of enzymatic variants unable to perform an efficient catalysis. This enzyme is responsible for one of the catabolic pathways of the inhibitory neurotransmitter GABA, which is essential for motor control.
When the levels of GABA are altered, there are pathological manifestations both in the neurological and motor fields. Patients with this rare disease are identified in pediatric age and present with motor and developmental disorders.
A research group of the university, directed by Mariarita Bertoldi, professor of Biochemistry in the department of Neuroscience, biomedicine and movement, is working to arrive at a synthesis of a more stable enzyme, a fundamental prerequisite for achieving precision therapy with the approach of Enzyme Replacement Therapy, which consists in the use of a healthy (wild-type) enzyme in order to replace the non-functioning one produced by the patient. The research obtained funding from GC Pharma, a well-established pharmaceutical company which, among others, has as its commitment the treatment of rare diseases.
“Through bioinformatics and biochemical methods – says Bertoldi – super stable variants of SSADH will be produced, which will be tested in solution and whose structural and functional properties will be evaluated. In collaboration with the group of Prof. Tikkanen of the University of Giessen, in Germany, the efficacy of these variants will be assessed in a cellular model and in an appropriate mouse model, a prerequisite for the clinical trials”.
