1. How did you cross paths with Khondrion?

I have crossed paths with Jan Smeitink, Khondrion’s CEO and Founder, multiple times at various international mitochondrial medicine conferences over the past decade. We first worked together when we co-chaired the 2nd Wellcome Genome Campus Mitochondrial Medicine Conference in 2016 in the UK. Jan and I have also worked on a few publications together since 2014, starting with our work on the Common data elements for clinical research in mitochondrial disease project run by the National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health (NIH) and also when the Children’s Hospital of Philadelphia, where I work, participated as the US site for the validation of the International Pediatric Mitochondrial Disease Scale study published by Jan’s group in 2016.

 

  1. How will the Scientific Advisory Board help Khondrion to achieve its goals?

The group that Jan has brought together is comprised of experienced leaders from around the world who can give Khondrion direct guidance related to challenges, needs, and opportunities in mitochondrial disease. We’ll be able to vet their data together, share our experiences and perspectives, and help strategise on key activities the company pursues such as clinical trial design. Not only will we be able to offer complementary viewpoints on clinical operations, but our international experiences will be especially useful – each  of us brings unique perspectives on country-specific regulatory requirements that guide therapeutic development, including preclinical research as well as clinical trial design and ethical conduct, to ultimately gain approval of effective therapies for mitochondrial disease. We’ll also be able to connect Khondrion to international clinical research organisations, to enable them to access the best teams to help conduct their trials.

 

  1. Tell us about your career and how you started in the mitochondrial disease space.

I graduated from college and medical school as part of a 7-year BA/MD combined programme at the George Washington University School of Medicine in Washington, DC in 2000. I then completed a 5-year Paediatrics and Clinical Genetics residency programme at the Rainbow Babies and Children’s Hospital and Case Western Reserve University in Cleveland, Ohio.  At the point when I began working in genomic disease, it had only been a decade since the first mitochondrial disease genes had even been discovered, so it was still a new medical field. I was fortunate to have outstanding biochemical genetics mentors in the Center for Inherited Disorders of Energy Metabolism (CIDEM), who exposed me to patients with mitochondrial disease and biochemical methods to investigate their complex energy dysfunction. I was particularly inspired by a pre-school age child whom I met in 2001 who had been previously healthy but recently had been diagnosed with mitochondrial disease after a muscle biopsy when she experienced a sudden metabolic stroke that prevented her from breathing on her own. I watched the senior doctor try to explain to her devastated mother, sitting at a small table in the intensive care unit, that while the child’s mitochondria had failed her, the cause was unknown and nothing could be done to fix the mitochondrial problem. Through observing this interaction and the realisation that there must be a genetic cause for such a devastating disease in a beautiful young child, my intrigue was sparked along with a strong desire to dedicate my career to help figure this out and prevent future children from dying without hope of an answer or effective therapies.

 

  1. What do you see as the biggest challenges in the mitochondrial disease space today?

The lack of safe and effective therapies that have been approved by regulatory agencies around the world remains the biggest challenge for mitochondrial disease. We have now discovered that there are hundreds of specific genetic causes, encompassing many major subtypes, of mitochondrial disease. This understanding means that we need to develop an arsenal of regulatory-approved, highly potent, and safe therapies so that we can tackle and treat as many aspects of mitochondrial diseases as possible. In the early days, there will only be therapies for some types or aspects of mitochondrial diseases, but we have to work together on the best way to get through each approval that will incrementally build our therapeutic options.

The international mitochondrial disease community is amazing because we are tight-knit and have matured together over time to mechanistically understand and diagnose diverse forms of mitochondrial disease. Together, we’re able to readily collaborate and share our knowledge and experience to get well-designed trials for current therapeutic leads going and continue to work on the development of additional therapies. Over the past decade there have been a growing number of cell and animal model studies that demonstrate mitochondrial diseases are treatable disorders. The next step is to effectively translate the knowledge we have to drug formulations that are properly made, absorbed, rigorously tested in clinical trials, and to demonstrate the meaningful improvement to patients’ survival, function, or feeling that is necessary to gain regulatory approval for their clinical use.

 

  1. What other mitochondrial disease projects are you interested in/working on?

I am proud to have built a world-class Mitochondrial Medicine Frontier Programme that integrates clinical care and research at the Children’s Hospital of Philadelphia (CHOP), with a singular focus on our mission to diagnose and understand mitochondrial disease and improve the standards of care and health outcomes for affected patients of all ages. I’m passionate about helping mitochondrial disease patients and their families across their journey from the time their disease is diagnosed to throughout their disease management, developing innovative diagnostics, objective outcome measures, natural history studies, and clinical trials that will be essential to realise effective therapies. Using innovative approaches that harness genomics together with minimally-invasive in vivo assessments to diagnose mitochondrial dysfunction, and its cause in individual patients, is essential to help guide appropriate care and develop effective therapeutic plans.

What really drives my passion today is coming up with the next generation of precision therapies for mitochondrial disease by using rationale, data-driven approaches in a complementary suite of genetic models of mitochondrial disease. This approach, which I call therapeutic cross-training, rigorously evaluates the safety and efficacy of a candidate therapy before it is ever tried in a mitochondrial disease patient.  

I’m truly encouraged by how quickly developments in research and potential therapies have occurred in the mitochondrial space, which has really accelerated in the last few years.  I’m more hopeful than ever that our community’s continued teamwork will soon bring in a new era with a range of regulatory agency approvals for therapies that begin to effectively treat the many different types and manifestations of mitochondrial disease. Then, we really will be able to prevent future children with mitochondrial disease from dying without hope of an answer or effective therapies.

 

  1. What is your coffee order?

Actually, I’m not a fan of coffee, but very much prefer tea! My tea of choice is homemade, non-fat, soy masala chai.