Hereditary Spastic Paraplegia Type 7

The hereditary spastic paraplegia type 7 (HSP 7) and spinocerebellar ataxia type 28 (Sca28/AFG3L2) are rare devastating genetic disorder caused by mutations in the SPG7 and AFG3L2 gene encoding the proteins that form a complex named the m-AAA protease. Mutations in the genes are known to affect the energetic function of mitochondria and then lead to the major signs and symptoms of this disease. Unfortunately, how they do so is still poorly understood and one of this lacks of knowledge is certainly the absence of treatment. These human genes possess homolog gene in Saccharomyces cerevisiae yeast (unicellular organism model less complex than the human cells) that name are YTA12 and YTA10. In this organism, the absence of these genes leads to cell growth retardation on a respiratory medium (respiratory phenotype), that is to say a medium containing as energy source only a substrate necessarily making use of mitochondria. This organism can thus be exploited for several objectives: (i) To better know and better understand the molecular mechanisms of these pathologies in order to identify new therapeutic targets, (ii) To identify new genes involved in the compensatory pathways for the implementation of metabolic treatments, (iii) To identify new molecules for the establishment of pharmacologic therapeutic treatments, (iv) Implement treatment that is it metabolic, genetic or pharmacologic to help patients with spastic paraplegia type 7 (HSP7) or spinocerebellar ataxia (ASC) type 28, (v) Use all of these results to also help patients with other pathologies of the group of spinocerebellar degeneration disease, especially those which can’t be easily modelled and for which research of molecules is limited.


Contributing Members

Dr. Jean-Paul Lasserre
Pr. Cyril Goizet
Dr. Isabelle Coupry
Dr. Patricia Fergelot
Dr. Christelle Durand

National and International Collaborations

Dr. Guillaume Banneau [Centre de génétique moléculaire et chromosomique, CHU Paris-GH La Pitié Salpêtrière-Charles Foix – Hôpital Pitié-Salpêtrière]
Pr. Michel Koenig [Laboratoire de génétique moléculaire – IURC – Institut Universitaire de Recherche Clinique, Montpellier]
Pr. Alexandra Dürr Réseau SPATAX [Paris]