MDF is pleased to announce that Dr. Melissa (“Missy”) Dixon, a Research Associate in the Deptartment of Neurology at the University of Utah, has been awarded a 2016-2017 postdoctoral fellowship.

Dr. Dixon’s research proposal is titled “Evaluation of Functional Connectivity as a Brain Biomarker in Congenital Myotonic Dystrophy.” In this study, she and her colleagues will use magnetic resonance imaging (MRI) to evaluate connectivity networks in the brains of children with congenital-onset myotonic dystrophy (CDM) to see if they differ from those of children without CDM, whether they change over a one-year time period, and whether the MRI results correlate with data from neuropsychological testing.

Dr. Dixon has an extensive background in clinical psychology, neuropsychological testing and clinical trial coordination. She received her doctorate in counseling psychology from the University of Utah in December 2015. We recently talked with Dr. Dixon to learn more.

MDF: There was a time when most children with CDM didn’t survive very long. Do they have a better prognosis now?

MD: Oh, absolutely. I would say that kids with this disorder have a better prognosis than they did a decade ago. We now know that respiratory and feeding problems can be life-threatening, and we’re better equipped to work with those issues from the start.

MDF: What is known so far about the neuropsychology and the brain abnormalities in children with congenital-onset myotonic dystrophy?

MD: Networks in the brain are kind of like a highway system. You can get from Illinois to Colorado by taking Interstate 80, but if there’s a block in that road or a piece of the road that’s missing, you have to take a different route to go around it. 

I don’t know if there are fewer “interstates” in the brains of children with CDM compared to those of children without CDM, but it may be that they’re using more roundabout pathways for getting from one place to another. I think the networks are different [from those in unaffected children.]  

People have used resting-state functional MRI [fMRI] during the resting state [without an attentional focus] to look at brain connectivity in kids who have autism, and they’ve found that it’s sensitive enough to show that there are differences in their connectivity networks. 

Earlier DM studies relied on structural imaging techniques. These can demonstrate a wide range of changes, but they’re not well correlated with clinical outcomes, such as IQ.

We think that by using fMRI we’ll be able to look at connectivity differences in these brain networks and see if they change over time in kids with CDM. 

MDF: Will this study be helpful in telling parents what to expect as their child matures?

MD: We’re hoping to be able to demonstrate changes over time by looking at blood flow in the brain using resting-state fMRI, at baseline and then at a year from baseline.

We’ll be tracking neuropsychological measures, such as executive function and IQ assessment. We’ll also look at adaptive behavior, at how a child is functioning, through a questionnaire that a parent or caregiver will fill out.  At the completion of the study, we would hope to tell parents where a child may have the most learning difficulty, and design interventions to approach those learning difficulties.  

MDF: If you do see abnormalities in connectivity in the brain, what are the possible implications?

MD: We know that cognition is impacted in CDM, but there is not a very sensitive way to see how this changes during the course of a short period of time, like during a drug trial. This technique could become an endpoint for a clinical trial to test the effect of a potential drug or therapy.

MDF: Is it possible that something like, say, DMPKRx, which is being developed by Ionis Pharmaceuticals, could have an effect on the brain, if it could be made to cross the blood-brain barrier?

MD: If not that particular therapeutic, then perhaps another, could potentially slow or halt the progression of the brain changes in this disease as we learn more about them.

MDF: Can you say more about the fMRI study?

MD: We’ll be enrolling 20 participants with CDM, ages 7 to 14, and we already have a control group for comparison. We’re not recruiting yet for the fMRI study; we’re still at the IRB [institutional review board] stage, applying for study approval. We hope to start recruiting in June 2016, and we’ll be posting that on the MDF site when we do. [Studies are listed at the MDF Study and Trial Resource Center under the Current Studies and Trials tab.]

We do, however, have an ongoing study of the natural history of CDM here at the University of Utah, and we hope to recruit some participants for the fMRI study from that group. [The natural history study, which is open, is Health Endpoints and Longitudinal Progression in Congenital Myotonic Dystrophy. Read more about it at the MDF Study and Trial Resource Center under Current Studies and Trials.]

We’ve done neuropsychological testing with the children in the natural history study. The children are all different, and that’s what makes CDM so interesting. The cognitive piece is fascinating. That profile for them is definitely varied, and I think that some of the measures that we’ve been using are just not sensitive enough to understand what’s going on.

I chose 7-year-olds as the lower cut-off age, because they have to stay in the fMRI scanner for 20 to 30 minutes. That can be difficult or scary for any child, and children with CDM sometimes have sensory issues. They’ll have something that’s like a fish tank for them to watch during the scan. It’s not like a movie, where they’d be actively thinking about things, but they’ll be looking at something.

MDF: You have a broad background in clinical psychology. What led you to study children with myotonic dystrophy?

MD: In 2013, when [neuromuscular disease specialist] Dr. Nicholas Johnson came here from the University of Rochester, I became interested in people who have myotonic dystrophy, particularly congenital myotonic dystrophy. I’m interested in understanding the neuropsychological differences in this population. There isn’t a whole lot of known information about congenital myotonic dystrophy and neuropsychological function.

MDF: Did you know that another MDF research fellow, Dr. Ian DeVolder, is doing a study of fMRI in adults with type 1 DM?

MD: Yes, I saw that. That was great to see that someone is doing something very similar in adults. I’m sure our paths will cross as we move forward in our careers. Hopefully, both of our efforts will better define the neuropsychological dysfunction throughout the life spectrum.