Ask the Mito Doc – March 2025 Q&A

All answers today are based on personal experience of the participants. As always, please consult your personal physician prior to taking any action.

Ask the Mito Doc – March 2025: Clinical Trial Readiness & Clinical Research Pavilion Updates

Clinicians:

· Zuela Zolkipli Cunningham, MBChB, MRCP, Children’s Hospital of Philadelphia, PA

· Damiano Zanotto, PhD, Stevens Institute of Technology, Hoboken, NJ

· Jose Antonio Adams MD, Mount Siani Medical Center, Miami Beach, FL

· Nicole Wilson, UMDF Program Manager

Q: How many patients have been engaged with the CRP in terms of the data being collected in both patients and healthy controls?

A: Zuela Zolkipli Cunningham, MBChB, MRCP: It’s incredibly important and incredibly successful what we’ve done, Phil, with your idea. So, for the patients and families, first and foremost, our understanding and demonstration of the impairments in our patients prior to any drug interventions is key because the FDA understand by the literature what’s available and out there, that is, of what impairments are there, but they really need to hear from you and to see our assessments, the magnitude and depth of the impairments and how they affect your quality of life. So, we conducted our measurements of the MM course because we needed to show the measurements that we measure, which is strength and balance. But I have had some feedback from the FDA to say, well, that’s not function, that’s not enough. So, what do we do about this heterogeneity, Phil? It’s really important, therefore, that we provide more and keep trying to provide more and keep thinking how else to measure this. We’re also asking for quality-of-life measure surveys to be conducted at the conference. And together, when we put together the whole package, which is an adequate number of patients, which we really did; in 2023, I had to submit an urgent IRB approval to increase the number of patients we were allowed to assess. So, we were really wowed that year at the interest of patients and willingness. That was really incredible. But also, the fact that we had scientific participants at the conference, including industry, who wanted to learn about these assessments, what they feel like, how much burden it feels. So, participating and producing what’s very difficult to get control data. And control data is essential to show in any type of assessments clinically. And so, we were able to collect, I think, 30 control assessments in the first year. The second year we got more, 40 assessments children and adults, by the way. So really, really important. It’s helped multiple data analysis sets that we have just by doing these clinical track ability and assessments.

Q: What is it like signing up for a clinical trial at the Clinical Pavilion Mito Medical Conference? What can people expect and what should they wear to participate?

A: Philip Yeske MD: The process of going through a number of tests will take about 90 min. Which really speaks to the importance of signing up early, get your time slot and complete as much of the consenting right ahead of time. But there will be some work necessary at the conference for ETIO as well. And then another practical matter.

A: Zuela Zolkipli Cunningham, MBChB, MRCP: Wear comfortable shoes, please wear comfortable sneakers. It can’t be flip-flops. And wear comfortable clothes. We don’t want anything restrictive because you are going to be lifting your arms and lifting your legs. And please come with a water bottle. We don’t want anybody dehydrated. Ideally, you wouldn’t come straight after a meal because, you know, with a full tummy, that wouldn’t be comfortable. The sign-up sheets help our organization, but we welcome any walk-ins. That’s why we’re bringing four physical therapists this year.

Q: Ultimately, what is the overall goal for designing and developing these insoles? Is it for gait analysis at home? Could it be remote assessments in a clinical trial?

A: Damiano Zanotto, PhD: Ideally the technology is versatile enough to where it can be used both in controlled environments, so in the clinic, in a hospital hallway, but also in the real world. So even though we started in control environments, the ultimate goal for us is to be able to extract this stride by stride the special temporal and kinetic parameters from real-world data collected over an extended time period. And in fact, we just concluded last week testing with our first study participant where we use this technology to collect over 200 hours of gait over 30 days. So yes, the ultimate goal is to kind of assess the real-world data. In terms of utility, the hope is that by leveraging real-world data, we can extract more sensitive parameters related to working functions. And eventually, this can be used in drug development to speed up the process of approval for these new interventions.

Q: It’s really important for us all to understand that the gait analysis is not something new. It’s been around for a while, but certainly there are some commercially available tools out there. I hope you wouldn’t mind just outlining some of the differences or some of the novel concepts to your insoles in comparison to something that’s already available.

A: Damiano Zanotto, PhD : Very briefly, the main difference or the main unique feature of our device compared to other devices that are available lies in its ability to measure both the spatial temporal and kinetic. So, parameters related to time and motion as well as forces. In a very small form factor that is socially acceptable. And that is not the case, for example, with a multi-sensor body worn device. Those are great for in lab testing, but not as feasible for continuous monitoring, gate monitoring in real world environment. And then compared to more established technologies such as the wrist worn devices, our technology can provide more accurate a measure of stride-by-stride parameters, which is typically not possible with wrist-worn devices due to their location in the body. We can assess the motion of the feet directly because we have sensors essentially attached to the feet.

Q: Is the gait analysis based on your insoles for mito patients distinct from other movement disorders?

A: Damiano Zanotto, PhD: So certainly, having that flexibility to measure a broad set of spatial temporal and kinetic parameters helps to narrow down the subset of parameters that are more sensitive depending on the impairments we saw. But yes, definitely the patterns that we see during the six-minute walk test, for example, are different between different clinical populations.

Q: I have a LifePro motion platform – is it Similar to Gentle Jogger? I think the question more is about vibration plates and passive exercise machines. How does that compare to the gentle jogger?

A: Jose Antonio Adams, MD: Vibration plates go at a much, much, much faster frequency. They go at a frequency of 30 hertz, 15 to 20 hertz. Our motion is at approximately anywhere between two to three hertz. And so, it is the difference in frequency makes a huge difference. Why? Because the amplitude of pulsations that are induced by vibration are also smaller. In other words, if you were able to generate the g-forces that we generate with the motion platform on the vibration, it would not be tolerable. So that’s a very, very, very important question that vibration therapy is inducing pulsation, yes, but it’s inducing it in, very, very tiny pulsations at an extremely high frequency. And we believe and some of our basic science data shows that frequency is also very important