Authors: Lauren Pulling
Recent years have seen an increase in drug repurposing, an area which itself is fast becoming a hot topic. In this interview, we speak to Elena Minakova, a Fellow in Neonatology at the University of California Los Angeles (UCLA) who is investigating a role for Melanotan-II in reducing social deficits in autism. The drug is, as yet, unapproved by the US FDA, yet has sprung up repeatedly in recent years both in research and as a commercialized product, making this new research particularly interesting.
Could you tell us a little about your background and what first sparked your interest in autism physiology and behavior?
From an early age, I recall being fascinated by the mystery and intricate workings of the brain and mind. I dreamed of becoming a doctor ever since the age of five but always thought I would have a neuroscience-based focus in my pursuits. As an undergraduate at the University of California, San Diego (UCSD; CA, USA), I majored in Physiology and Neuroscience and afterwards, pursued a research-based Master’s in Neuroscience at UCSD. My work at the time was in the field of developmental neurobiology and explored signals involved in neurotransmitter specification during early development of the spinal cord. I was drawn to the neurodevelopmental branch of neuroscience due to the increased plasticity of the nervous system and opportunities to provoke positive changes within aberrant processes with potential for clinical applications.
After completion of the Master’s of Science degree, I went to medical school, completed residency and am currently a Fellow in Neonatology at UCLA. During my fellowship, I continued my enthusiasm for neurodevelopmental neurobiology research and was particularly fascinated by autism research. In recent years, the development of ‘autistic’ rodent models has helped deepen our understanding of how both genetic and environmental factors can lead to alterations within the brain to manifest as autism. Given the availability of autistic rodent models, this was the best match for my goals to assess therapeutic interventions in a neurodevelopmental disorder with the possibility for translational application.
You recently presented your work, ‘Melanotan-II reverses autistic features in the environmental mouse model of autism’, at Neuroscience 2016 – could you give an overview of this?
My research was aimed at testing the effects of Melanotan-II (MT-II) on a validated environmental mouse model of autism. MT-II is a drug with the ability to bind melanocortin receptors on oxytocin neurons, followed by subsequent oxytocin release. In the past several years, oxytocin, a pro-social neuropeptide, has received attention as a possible medication for autism. However, one of the issues with oxytocin administration is its short half-life in the blood stream and poor permeability from the blood to the brain. Of note, MT-II has a cyclical structure, which allows for easier blood–brain permeability followed by endogenous release of oxytocin.
We produced autistic mice through in utero exposure to maternal inflammation and then implanted a subcutaneous pump containing the MT-II. A cannula was placed into the ventricles of the brain and the drug was administered continuously via the subcutaneous pump over a 7-day period. The autistic mice showed significant improvement in their social interactions with several behavioral metrics normalizing to levels found within normal mice. Of interest, the autistic mice receiving the drug were full-fledged adults, suggesting the ability to provoke changes even at less plastic time points in development.
How much do we already know about the role of the melanocortin system in socio-emotional behaviors?