Dr. Plavi Mittal earned her Ph.D. in Biology from Brandeis University, and did her postdoctoral research in molecular oncology at Harvard Medical School. She was also a management consultant at a global consulting firm, where she worked with leading pharmaceutical companies.
After a family member was diagnosed with a rare muscular dystrophy, LGMD2B/Miyoshi, Dr. Mittal helped create the Jain Foundation. Over the last 12 years, she has led the JF team as President & CEO, and together, they partnered with dysferlinopathy researchers to realize gene therapy clinical trials and the hope for a cure. Repeatedly, Dr. Mittal has seen patients with rare disease struggle to reach a diagnosis and find a treatment best for them, despite the scientific breakthroughs advancing therapies for their condition.
Through her new non-profit organization based in Seattle, Washington, In-Depth Diagnostics [www.indepthdiagnostics.org], Dr. Mittal will continue to support the mission of the Jain Foundation while addressing this larger patient need by providing genome-level sequencing and analysis. IDD’s national diagnostic program is an unprecedented effort that will raise standards for diagnosing rare diseases and also fuel a research consortium focused on improving clinical care.
Can you tell us more about your background before starting the Jain Foundation? How did you first become interested in science, biology, and oncology?
I was always interested in Genetics and Biology for as far back as I remember. I think my interest started when I read the book, Lives of a Cell by Lewis Thomas. I was fascinated with the diversity, the resilience and the complexity of biological organisms. Later, as a PhD student, I was very keen to work on problems that would impact people suffering from diseases today. I feel that we have an urgent mission to connect the dots from everything we have already learned.
Can you tell us about your work at the Jain Foundation over the past decade, and how that led you to start In-Depth Diagnostics (IDD)?
At the Jain Foundation, we were completely focused on pushing research towards a cure for LGMD2B, a rare form of muscular dystrophy. Over the years, our strategy of uniting researchers with the relevant expertise proved successful, and we set the stage for clinical trials. Then, I learned first-hand what industry has been struggling with for years: rare diseases are difficult to research, because the patients needed for clinical trials are very difficult to find. With the hopes of finding enough patients to develop a meaningful trial for LGMD2B, the Jain Foundation developed a free diagnostic program. We put together a panel of 35 genes linked with diseases that would have a similar presentation as our disease of interest, LGMD2B. We were able to screen 2,500 people and diagnose dozens of LGMD2B patients. This work confirmed my belief that genetic testing is a quick and efficient clinical tool for complex diagnostic cases.
What convinced you that there is a need for better diagnostics for rare diseases? Why is diagnosis so important for these patients?
While the diagnostic program was very successful at finding LGMD2B patients for the Jain Foundation patient registries, over 60% of the patients tested received no diagnosis. I felt a personal dedication to these patients who were offered the hope of an answer, only to be let down by the inherent limitations of a panel-based approach. These patients would have to wait many more months while they sought other opportunities for genetic testing, if they had the resources to do so. Given the falling price of human genome sequencing and clinical analysis, performing one thorough analysis seemed to me to be more efficient and effective than repeated genotyping. By focusing on providing comprehensive genetic analysis to these patients, I have the opportunity to provide an under-utilized, powerful diagnostic tool to patients in critical need of targeted treatment plans. And by empowering patients with their genetic diagnosis, patients can seek out research and clinical trials best suited to their condition.
How did you choose whole genome sequencing, and how does this open up new avenues for research?
By performing whole genome sequencing, we will be assessing as much of the human genome as technology currently allows. This means that, in addition to identifying known pathogenic variants for diagnostic purposes, we will be able to uncover nuanced patterns in other regions of the genome. We hope that, by strategically combining our bioinformatic analysis with information about patients’ symptoms and traits, we can highlight promising avenues for therapy development for a great number of rare neurological diseases.
What do you think distinguishes IDD from other genetic testing/analysis/diagnosis services available today? Why do you think now is the right time for IDD to open its doors?
I’ve been considering this very question for months – right now, the clinical and academic applications of genomics are booming. So many groups and companies are launching large projects or consumer products that the market appears saturated with personalized technology. However, as I’ve built IDD’s program, it has become painfully clear that the vast majority of commercial products are not able to offer a clinical diagnosis to patients seeking one, or they do not perform a full genome analysis at all. Many insurance plans do not cover comprehensive genetic testing, and patients cannot afford to pay out of pocket for this additional test when they are facing a myriad of diagnostic procedures. By offering our services to patients at no charge, and performing full genome sequencing/analysis for clinical and research applications, we are the only program working to deliver this cutting edge technology directly to patients who could benefit most.
What is your vision for In-Depth Diagnostics going forward?
My vision is for In-Depth Diagnostics to become a leader in rare disease diagnosis and patient engagement. By gathering evidence supporting the efficiency of genetic screening for difficult-to-diagnose neurological conditions, I hope to influence a shift in clinical standards of practice. I don’t plan to measure the success of my program only by the number of patients diagnosed; my success is also contingent on creating an accessible community where patients can learn about the unique ways patient participation can accelerate and influence the development of rare disease therapies. By empowering patients and generating sufficient data, I hope IDD’s program will spark therapy development for a number of rare conditions.
What directions do you see genomic testing (including analysis, diagnosis, and counseling) taking in the future? Do you see a lot of change happening in this area? Do you think these changes are positive or negative? Why?
I think we are rapidly moving to the era of unlocking all of DNA’s mysteries, and really charging forward and diagnosing most conditions in much less time. I am not as sure that we, as a species, will take care to provide adequate support, guidance and counseling along with the diagnosis. I hope we do, and IDD is definitely striving for that deep level of engagement with the patient, becoming a source of support for them.
The changes unlocking of the DNA will bring to diagnosis is a big step forward in the right direction. Everything starts with diagnosis: by naming the suffering – then we can begin to understand the origins and begin to develop treatments.
How can members of the CEHG community get involved with In-Depth Diagnostics?
Once sufficient data is collected, IDD hopes to launch a major research effort that will combine groups across academia and industry who are studying human disease, developing therapies, or performing other computational biology projects that may benefit from data such as ours. Any researcher from the CEHG community who is interested in working with IDD’s curated database should contact the foundation for application.
CEHG’s core values are “collaboration” and “interdisciplinarity.” Are there ways you hope IDD will embody these values as well?
Absolutely! While genomic data is at the heart of this program, I know that progress in clinical care for rare diseases will only occur after combining data from numerous other health factors and biological perspectives. To put our program’s data to the best use, we must rely on collaborations with groups across industry and academia to elaborate on relevant findings and push the genetic information towards a meaningful application.
What advice would you give to early career scientists, having worked in both academia and at foundations with a patient-centric focus?
My advice is to always look 10 steps ahead and find the connection to how your research will help humans. This exercise makes everything so much more focused, and also very meaningful.
What advice would you give to patients?
Advocate for yourself; there are answers your doctor may not know. Participate in all aspects of drug development. Read and get educated about your disease.