Professor Francesco Muntoni is a clinical paediatric neurologist with an interest in molecular aspects of neuromuscular disorders. He joined the Neuromuscular Unit in 1993, and became the Head of the Unit in 1996.
Important area of Professor Munoti’s work has been the establishment of international collaboration networks allowing the identification of a number of disease genes involved in neuromuscular disorders (12 novel genes in collaboration with external collaborators). The Dubowitz NM Group has identified 2 novel loci for forms of congenital muscular dystrophy and three novel disease genes. One of these 2 genes (FKRP) proved not only to be relevant for a rare form of congenital dystrophy, but also for a very common form of mild limb girdle muscular dystrophy.
Form a translational research perspective, Prof Muntoni is interested in manipulation of splicing of genes involved in neuromuscular disorders, for example the control of splicing of the SMN2 gene involved in spinal muscular atrophy. In collaboration with Prof Eperon, Prof Muntoni’s group has identified a tailed antisense oligonucleotide which carries sequences that are involved in the recruitment of splicing proteins and induce a crucial exon inclusion in SMN2. A different approach, the use of antisense oligonucleotide to induce exon skipping in Duchenne muscular dystrophy, culminated in a Department of Health funded grant to establish a consortium for a phase I/II therapeutic trial of intramuscular antisense morpholino oligonucleotide in Duchenne muscular dystrophy that started in 2005 and was completed in 2008 (Muntoni PI). Prof Muntoni subsequently obtained an MRC translational research grant to extend this study into a dose escalation, repeated intravenous morpholino antisense administration into young boys with Duchenne. The results of the study were very encouraging and have led to additional funding to perform additional studies both to target Duchenne individuals at later stage of disease progression, but also to assess the efficacy and safety of a new generation of antisense oligonucleotide, with the plan to perform a proof of concept study in 2013. These studies are supported by the GOSH Biomedical Research Centre and from the UCL MRC Neuromuscular Translational Research Centre, of which Prof Muntoni is the Deputy Director.