From the forefront of medical research to the front lines of patient care, scientists and clinicians at the Mayo Clinic Center for Individualized Medicine are making notable progress in rare disease diagnostics and treatments. Patient by patient, they are dedicated to bringing hope, answers and healing to those who have tirelessly searched for solutions to their conditions. 

The pioneers in the field, including Margot Cousin, Ph.D., and Filippo Pinto e Vairo, M.D., Ph.D., are harnessing emerging technologies, individualized therapies and artificial intelligence (AI) to drive meaningful progress for the 300 million people worldwide who have a rare disease.  

"It's a really exciting time for rare disease therapeutics," says Dr. Cousin, a translational genomics researcher at the Center. "We now have the ability to understand how to impact the genetic mechanisms of disease. The challenge now is really applying that knowledge and applying those tools and translating them into therapeutic solutions that are deliverable for more people." 

Rare diseases, defined as conditions affecting fewer than 200,000 people, are a significant focus at Mayo Clinic. Annually, Mayo Clinic evaluates thousands of patients grappling with these conditions. In fact, approximately 15% of patients seeking a second opinion or treatment at Mayo Clinic are diagnosed with a rare disease. 

Pioneering precision medicine for rare diseases

Dr. Cousin's rare disease research is centered on innovative new treatments, including antisense oligonucleotide — an ultra-individualized medicine strategy that can be tailored to a single patient each time. The therapy uses custom-made RNA, the messenger in cells, to shut down or fix faulty genes without altering DNA. 

"With antisense oligonucleotide drugs, we can reduce the amount of gene product that's being made in the cell and reduce the disease-causing effects of that genetic alteration," Dr. Cousin says.  

Dr. Cousin is leading efforts to initiate the first individualized clinical trial of an experimental antisense oligonucleotide drug through the Center for Individualized Medicine later this year. She also anticipates the expansion of other cutting-edge treatments, including CRISPR gene editing, a technology that enables precise changes in DNA sequences, and gene therapies, which add, alter or remove genetic material in cells to treat or prevent diseases.  

Critical role of definitive diagnosis with cutting-edge technologies

Such innovative treatments stem from breakthroughs in diagnostics and biomarkers. Dr. Pinto e Vairo, director of the Mayo Clinic Program for Rare and Undiagnosed Diseases, emphasizes that a definitive diagnosis is the crucial first step toward a treatment. 

The Program for Rare and Undiagnosed Diseases comprises a multidisciplinary team of genetic counselors, genetic counselor assistants, clinical researchers and geneticists, all united in the pursuit of answers for patients. Their mission is to empower Mayo Clinic providers to integrate genomic testing directly into patient evaluations within their departments, since genetic testing can play a pivotal role in diagnosing inherited conditions.  

In 2023, the Program team facilitated genetic testing for 860 patients with a suspected rare disease and successfully identified genetic causes for undiagnosed diseases in nearly 30% of patients. 

Dr. Pinto e Vairo says cutting-edge genome sequencing technologies, which often use AI to scour volumes of data, are helping clinicians precisely pinpoint more disease-causing genes, leading to an increase in definitive diagnoses.  

Rapid genome sequencing accelerates the identification of genetic abnormalities across a patient's entire genome – all 3 billion DNA base pairs — while targeted gene panels streamline the analysis by focusing on specific sets of genes linked to suspected conditions. 

"An emerging diagnostic approach we anticipate involves sequencing RNA together with DNA," Dr. Pinto e Vairo explains. "This could help us confirm predictions about how specific genetic variants in DNA may impact individual patients."  

Transforming lives with collaboration

Dr. Cousin and Dr. Pinto e Vairo emphasize this progress would not be possible without the dedication of countless collaborators. Organizations such as the Global Alliance for Genomics and Health, the Rare Disease Centers of Excellence network, National Organization for Rare Disorders, Undiagnosed Disease Network International, and other patient advocacy groups play a crucial role in raising awareness, funding research and ensuring equitable access to these advancements for all. 

"We're not just diagnosing diseases,” Dr. Pinto e Vairo says. “We're transforming lives, providing hope and answers and shaping the future of healthcare." 

Watch the Mayo Clinic Center for Individualized Medicine’s virtual grand rounds featuring Julia Vitarello, founder of Mila's Miracle Foundation, as she shares her inspiring journey in rare disease advocacy. Learn how her initiatives like the N=1 Collaborative and EveryONE Medicines are reshaping treatment paradigms. Hear firsthand about the challenges and successes in rare disease research and innovation. Expert panelists Erica Barnes, Margot Cousin, PhD, and Radhika Dhamija, MBBS, explore key topics in individualized medicine. 

Related Articles