Professor Nicholas Mazarakis
Pathways of neurodegeneration and gene therapy
We previously demonstrated that lentiviral vectors pseudotyped with rabies-G envelope can be injected into muscle, taken up at the motor neuron nerve terminal at the neuromuscular junction (NMJ), and expressed in the cognate motor neurons (MNs) in the spinal cord. Our research is aimed at designing improved versions of retrogradely transported lentiviral vectors for use in therapy of Motor Neuron Diseases such as Amyotrophic Lateral Sclerosis and Spinal Muscular Atrophy. We are investigating the molecular pathway of retrograde transport of the rabies-G pseudotyped lentiviral vectors in motor neurons. We are also using surface engineering to construct lentiviral vectors with improved tropism to the NMJ so as to to increase the efficiency and specificity of gene transfer to MNs in relevant disease models. In addition we are investigating neuroprotective and autophagic approaches for sparing striatal neurons from polyQ toxicity in in vitro and in vivo models of Huntington's disease. If these proof-of-principle experiments prove efficacious we will aim to translate them into clinical trials.
Clinical specialities relevant to: Neurology, Neurosurgery, Geriatric Medicine
Further Information http://www1.imperial.ac.uk/medicine/people/n.mazarakis/
Contact Details
Tel: +44 (0)20 7594 7024
