Dr. Paola Leone directs a collaborative research team that has pioneered gene therapy and drug research aimed at a cure for Canavan Disease. We have been aggressively funding her team and lab for almost twenty years.

A combination of clinical and experimental expertise are essential to unlocking the secrets of Canavan disease. In addition to her core group at the Cell & Gene Therapy Center at Rowan University Medical School in New Jersey, key members of Dr. Leone's multidisciplinary team are located at the University of North Carolina, the University of Pennsylvania (Children's Hospital of Philadelphia), New York University and the University of Illinois. Under her direction, these neurologists and biomedical researchers are perfecting gene and drug-based therapy for Canavan and other brain diseases.

Dr. Leone's team is currently testing the most advanced gene therapy vector in the world for Canavan disease

Over a decade ago, Dr. Leone and her core team spearheaded the first application of viral gene therapy to patients affected by Canavan Disease and reported long-term safety and clinical improvements in patients treated with gene therapy (Leone et al., 2012). In the process, Dr. Leone's team collected valuable natural history data (Janson et al., 2006) that will be used as a benchmark for future Canavan disease clinical trials.

Dr. Leone's team is currently testing the most advanced gene therapy vector in the world for Canavan disease, which was recently developed by her collaborators at UNC. Unlike all other gene therapy options, this newest gene therapy vector specifically targets the cells affected in Canavan Disease and holds a real promise for finally curing the disease.

Gene Therapy

Although extremely promising, gene therapy is only one approach to curing Canavan disease. Dr. Leone's group was among the first to propose a metabolic understanding of the disease. NAA is the main compound that is abnormally elevated in Canavan disease, and Dr. Leone's work is leading to a better understanding of the complex transport of NAA in the brains of patients with Canavan disease. In particular, Dr. Leone found that a metabolic deficit is a central feature of Canavan disease that underlies hypomyelination and cell loss (Francis et al., 2012). She also discovered that dietary therapy that fuels brain metabolism resulted in neurologic improvement and myelination in a well characterized animal model on Canavan Disease (Francis et al ., 2014 ), and proposed a clinical study to test this treatment option.

This work is leading to a better understanding of complex brain metabolism, with direct applications to Canavan disease as well as a broader significance for other brain diseases including Alzheimer's and brain cancer.

Drug Therapy

In terms of drug therapy, Dr. Leone and collaborators discovered the neurologic benefit of lithium citrate administration in Canavan patients (Assadi et al., 2010), which is currently one treatment option to help preserve brain function in newly diagnosed Canavan patients. Building upon this initial success, her collaborator Dr. Janson at the University of Illinois is developing new cell-based drug screening assays which hopefully will lead to more pharmaceutical options for Canavan and related conditions.

Finally, in work co-funded by the NIH and Canavan Research Illinois and partners in biotechnology, Dr. Leone is testing the benefit of human neural stem cell therapy, already approved for clinical use, in preclinical models.

While actively engaged in novel preclinical developments for a cure, Dr. Leone's team continues to assist with the management and care of Canavan patients worldwide and provides knowledgeable support on clinical care and genetic screening of rare mutations.