Rarecast

Diagnosing a rare disease can take years. When it’s a disease that’s never been identified before, the search for a diagnosis can be that much more difficult. Daryl Scott, associate professor of molecular and human genetics at Baylor College of Medicine, and colleagues diagnosed four patients on two continents with a never before identified rare disease in a day. The feat is recounted in a recent study published in the journal PLoS ONE (http://bit.ly/2oEXhy5). We spoke to Scott about the diagnosis, how it all came together, and what it says about the role of data and collaboration in medical detective work today.

Researchers at UCLA have developed a stem cell gene therapy treatment for children born with the rare, life-threatening condition ADA-deficient SCID, often referred to as Bubble Baby disease. Children born with this condition are without a functioning immune system and are kept in controlled and isolated environments because exposure to common illnesses or infections can be lethal. We spoke to the treatment’s developer Donald Kohn of the UCLA Eli and Edythe Broad Center of Regenerative Medicine about the stem cell gene therapy, the promising results he’s had restoring normal immune function in clinical trial patients, and why this approach holds promise in other rare conditions.

Legislation that would provide incentives to drugmakers to repurpose existing pharmaceuticals as rare disease treatments is once again in the works. Known as The OPEN ACT (Orphan Product Extensions Now, Accelerating Cures and Treatments), proponents say it would help address a gap in the drug development landscape. At one point, the bill had been folded into the 21st Century Cures Act, but had been stripped out before passage. We spoke to Max Bronstein, chief advocacy and science policy officer for the Everylife Foundation for Rare Diseases, about the legislation, why its needed, and what it will take to get passed.

The high cost of drug development and the small populations for individual rare diseases can make it difficult to attract drug companies to make the investment of time, money, and resources necessary to bring a rare disease drug to market. American MedChem, a non-profit drug company, is hoping to bridge a gap between the lab and the clinic, by using its small molecule expertise to advance potential rare disease therapies to a point where a drug company might seek to license them. We spoke to Robert Selliah, founder, president, and CEO of American MedChem, about its business model, what a non-profit can do that a for-profit pharmaceutical company can’t, and how it is prioritizing the projects it is pursuing.

Rare disease advocates, because of their diseases’ small population of patients, can find it challenging to muster the interest of researchers and drug developers to invest the money, time, and energy needed to discover and develop a therapeutic. One solution is to drive collaborations to leverage the limited resources of foundations and researchers and advance their efforts to a point where drug company may be willing to take over development. Support of Accelerated Research for Niemann-Pick C, or SOAR-NPC, represents such a model. We spoke to Cristin Davidson, a researchers and project manager for SOAR-NPC, about the organization’s approach, how its tackled various preclinical challenges common to rare diseases, and why the success it has enjoyed should be replicated by others.

Hallie Bae Barnard is an eight-year-old girl with Diamond Blackfan Anemia, a rare condition that has set her family and friends on a search for a suitable bone marrow donor. But her understanding of the need of others in a similar situation has her on a quest to find not only a match for herself, but for many others who are unable to find a life-saving bone marrow donation they need. We spoke to Jennifer Scott, a founding board member and vice president of Media and Communications for Hallie’s Heroes, about Diamond Blackfan Anemia, the challenges of finding bone marrow donors, and the impact the organization is having.

When Milo Lorentzen was born, concerns over his condition sent him to a neonatal intensive care unit where he spent the first ten days of his life. It began a medical and diagnostic odyssey for him and his parents. After six surgeries and undiagnosed global developmental delays, doctors identified a de novo gene mutation to his KDM1A/LSD1 gene that is believed to be the cause of his condition. His parents eventually launched the website Milo’s Journey to tell his story in the hopes of finding others with the same mutation. We spoke to Karen Park, Milo’s mother, about her family’s experience, the challenge of having a child with an ultra-rare disease of unknown consequence, and the experience of finding others with the same condition.

Edgar Kline Jr.’s family can trace its involvement with a rare genetic disease back to the 1700s. In fact, Hagerstown, Maryland, where his family settled, has a higher incidence of hereditary ATTR amyloidosis because of this common ancestor some in the town share. The disease which begins to manifest itself in middle age, can cause damage to the heart, nerves, and various organs. We spoke to Kline about the disease, the difficulty in getting an accurate diagnosis, and why he’s trying to raise awareness about it.

The Internet has opened up a world of information to rare disease patients, but it can often be hard to access, understand, or evaluate. Raremark is working to keep rare disease patients up to date with the latest information about their conditions through its online community built around disease channels. We spoke to Raremark founder Julie Walters about the website, how it curates information, and how its ultimately seeking to empower rare disease patients to make better decisions about their own care.

The translation of a drug from discovery to development faces a number of obstacles, but these can be amplified for rare disease therapies in part because of the smaller populations, heterogeneous nature, and often poorly understood development of a disease. The Catalyst program at the Clinical & Translational Science Institute at the University of California, San Francisco will be holding a one-day symposium on March 3 with leading researchers, drug developers, and patient advocates about the translational challenges rare disease therapies face and how to address them. We spoke to Cathy Tralau-Stewart, interim director of UCSF's Catalyst Program, about the upcoming symposium, the unique translational challenges rare disease therapies face, and what can be done to overcome them. To view the symposium agenda or to register, you can paste this URL (http://bit.ly/2lWmYbB) into your browser.

World Rare Disease Day, an annual international effort to create awareness for rare diseases, will take place February 28. This year, the theme is on how research brings hope to people living with rare diseases. This seemed like an opportune time to talk to Kenneth Hobby, president of CureSMA, about his organization’s efforts to drive research for spinal muscular atrophy, the most common genetic cause of death for infants. We spoke to Hobby about CureSMA’s strategy for research, the role the group played in helping to make possible the first approved therapy for the disease at the end of last year, and what other rare disease organizations can learn from its experience.

Last month, Children's National Health System, the world’s largest provider of care for children with rare genetic disorders, announced the formation of Children’s National Rare Disease Institute. Billed as a first-of-its-kind center focused exclusively on advancing the care and treatment of children and adults with rare genetic diseases, the National Organization for Rare Disorders has designated it as its first Center of Excellence of Clinical Care for Rare Diseases. We spoke to Marshall Summar, chief of Genetics and Metabolism at Children’s National and chairman of NORD, about the new institute, the ambitious vision for it, and the role it hopes to play in transforming care for people with rare diseases.

A group of rare, genetic, metabolic diseases known as lysosomal storage disorders are largely without treatments. Mark Noble believes one way of accelerating the development of therapies for this group of disorders is to look at them collectively instead of individually, and see whether existing drugs might serve as treatments. Noble, professor of Genetics and of Neurobiology and Anatomy at the University of Rochester Medical Center, recently co-authored a study in PLoS Biology (http://bit.ly/2kPbUzJ) that suggests repurposed drugs could address a common aspect of these diseases and provide therapeutic benefit. We spoke to Noble about his research, the findings of this common link in this group of diseases, and the potential implications for using already approved drugs to bring needed treatments to patients.

Sobi is a drugmaker focused on hemophilia, inflammation, and genetic and metabolic diseases. It is now pursuing its drug Orfadin, used to treat the metabolic disorder tyrosemia type 1, as a potential treatment for the metabolic condition alkaptonuria. It is also pursuing Kineret, its drug for the rare inflammatory condition NOMID, as a potential therapy for Still’s disease. We spoke to Rami Levin, president of North America for Sobi, and Len Walt, vice president and head of medical affairs of North America for Sobi, about the company’s evolution, its growing pipeline, and its effort to expand indications for its rare disease drugs.

The large number of rare diseases and the small number of patients afflicted with any one of them can help fuel a sense of isolation these patients feel. Sandra Shpilberg, CEO of Seeker Health, has interviewed many rare disease patients over time as part of her work to help drugmakers find participants for clinical trials. In a recent article on her website she argues that rare disease patients, regardless of their particular ailment, share much in common. We spoke to Shpilberg about the disease burden that rare disease patients face, how they may seek to address some of these issues, and why collaboration throughout the rare disease community is critical to creating better outcomes.

The search for a diagnosis can be a long and difficult journey for patients with a rare disease, but CrowdMed is offering a different way for them to find the answers they seek. The web-based service allows patients to tap a multidisciplinary team of experts to help them solve their medical mysteries. We spoke to Jared Heyman, founder and CEO of CrowdMed about the service, how his the experience his sister faced in getting a diagnosis for a rare disease led to its creation, and why the company, even though its backed by top-flight investors, is now turning to crowdfunding to raise capital.

Collaborations have become a critical aspect of the search for new treatments for rare diseases as drug companies, universities, research institutes, and patient groups are forging alliances to leverage their strengths. Outside this year’s J.P. Morgan Healthcare Conference, Global Genes will convene Rare in the Square in San Francisco’s Union Square to provide rare-disease focused companies and organizations a place to network at the heart of the week’s activities. We spoke to Michael Pistone, director of marketing, innovation & commercialization at Cincinnati Children’s Hospital Medical Center, about his hospital’s rare disease partnerships with drug companies, how the face of partnering in the rare disease space is evolving, and what he’s hoping for at this year’s Rare in the Square event.

Obsessive compulsive disorder, tics, anxiety, attention deficit hyperactivity disorder, and behaviors associated with autism spectrum disorders can be caused by a treatable autoimmune condition that is triggered by common infections. These conditions, known as PANDAS and PANS can often be misdiagnosed and wrongly treated to the detriment of the children with the condition. We spoke to Craig Shimasaki, CEO of Moleculera Labs, which has developed a diagnostic to determine if an individual’s neurologic or psychiatric symptoms could be caused by an autoimmune dysfunction. Shimasaki discussed these conditions, what we know about them, and how the availability of a diagnostic is helping change the way these patients are understood and treated. This is an encore presentation of an interview that first aired in April 2016.

For rare disease patients and their families, genome and exome sequencing may identify mutations that may be drivers of a condition, but nothing more. As families search for a name to put to a disease and look for treatments, finding others with the same condition and researchers working to understand and treat it becomes a critical part of the search for answers. Now researchers at the University of Washington have created MyGene2, a web portal for people with rare genetic mutations to connect with others with the same condition and researchers interested in their particular mutation. We spoke to Michael Bamshad, professor and chief of the Division of Genetic Medicine in the Department of Pediatrics at the University of Washington & Seattle Children’s Hospital, and Jessica Chong, one of the leads on the MyGene2 project at the Center for Mendelian Genomics at the University of Washington, about the portal, how it works, and what they are hoping to accomplish. This is an encore of an interview that first a

When Matt Wilsey daughter Grace was diagnosed with the ultra rare disease NGLY1 deficiency, he travelled the world to get a diverse group of researchers to work on finding answers. His approach to driving research, he says, comes from his experience as a Silicon Valley entrepreneur. We spoke to Wilsey about the experience getting a diagnosis for his daughter, what he learned from others who had gone before him, and the importance of open collaboration across institutions.