Henry Houlden, professor of neurology at the MRC Centre for Neuromuscular Diseases, University College London Institute of Neurology in England, was awarded an MDA research grant totaling $288,151 over three years to elucidate the genetic causes of severe forms of Charcot-Marie-Tooth disease (CMT) and other types of early-onset neuropathy. Identification of the causative genes could help optimize treatment strategies and accelerate new therapy development.
Please describe your current research.
We have built up a large series of genetically undefined inherited neuropathy patients. From this group we selected subjects, and collected DNA from parents and siblings as a trio or small family, with either white blood or skin cells, or muscle available for RNA and protein studies. We plan to identify and characterize the disease genes in this group using whole genome sequencing to identify the disease-associated variants, then use RNA sequencing to narrow down the mutation by identifying aberrant RNA splicing or reduced RNA expression (lost function) and subsequently characterize the disease genes in mammalian and patient cells.
We expect to identify a number of inherited neuropathy genes from this work. These genes will cause more severe, early-onset neuropathy but targeting the most aggressive phenotypes may reveal the more important disease pathways.
What inspired you to study CMT?
We see a large number of patients with severe and early-onset neuropathy, and many have no disease gene and for most there is no treatment. This sparked our interest to collect patient information and collaborate with neuropathy experts in the United States to accelerate our research.
What is your area of focus within the CMT field, and why is it important?
My focus is on finding genes and disease pathways.
By identifying genes we can give patients and families an exact diagnosis and by finding pathways we can discover potential therapies.
Why is it important that MDA continue to fund research in CMT?
MDA funding is vital to enable this research, and without it, this work would not go ahead. We have no government funding to support this work.
What do you feel people impacted by CMT can have the most hope about with respect to research right now?
There is hope from this work. We want to involve all patients with severe CMT, and we are keen to have the MDA’s help in connecting us with any patients and families that wish to be involved. We hope to find genetic causes to give a diagnosis, and the goal is to identify and promote the discovery of therapies.
Does your work have any potential implications for other disease fields?
Yes, there is overlap between severe early-onset CMT and other forms of neuropathy. The pathways discovered will inform studies for all disorders that cause degeneration of the sensory and motor nerves.
