RARECast

Charcot-Marie Tooth disease is a rare, genetic nerve condition that affects 150,000 Americans and nearly 3 million people around the world. Though the condition was first medically recognized in 1886, it is without an approved therapy. The CMT Research Foundation has been seeking to change that by addressing barriers to the development of therapies for CMT. We spoke to Susan Ruediger, founder and...

DNA-modified cells can behave unpredictably in the body and there is a risk that they could proliferate uncontrolled, cause severe toxicities, and even survive unchecked for months or years. Cartesian uses its platform technology to engineer RNA into cells, making time-controlled changes. The company is developing treatments for cancer, respiratory conditions, and autoimmune diseases such as myast...

Classic congenital adrenal hyperplasia, or CAH, is a potentially life-threatening rare genetic disorder characterized by an inability to produce the stress hormone cortisol while causing excess production of androgens, or male sex hormones. The condition has long-been treated with steroids, but about 70 percent of patients with the condition have poorly controlled disease. The problem is that it i...

The imbalance between the supply and demand for gene therapy manufacturing capacity is creating opportunities for contract development and manufacturing organizations. Forge Biologics is seeking to leverage its expertise in AAV gene therapy as a CDMO while developing its own pipeline of experimental gene therapies. We spoke to Tim Miller, co-founder and CEO of Forge Biologics, about the company’s...

Precision, safety, and durability are challenges for gene replacement and gene editing therapies. LogicBio Therapeutics says its GeneRide platform technology addresses these challenges by harnessing a natural DNA repair process. We spoke to Daniel Gruskin, chief medical officer of LogicBio, about the company’s platform technology, the advantages it provides, and the company’s lead experimental the...

Health records can be a rich source of data that can help provide an understanding of a rare disease and drive the development of therapies to treat them. But the siloing of this data, the use of inconsistent terminology, and the unstructured nature of aspects of these records all stand as barriers to harnessing their potential. The consumer health technology company Ciitizen is working to give pa...

The translational challenges of moving an experimental therapy from the lab to the clinic can stall the development of life-saving therapies, but Passage Bio has provided a unique solution to that challenge. The company’s strategic collaboration and licensing agreement with the University of Pennsylvania’s Gene Therapy Program leaves the discovery and preclinical work in the hands of Penn research...

Earlier the month the U.S. Food and Drug Administration approved Apellis Pharmaceuticals Empaveli to treat paroxysmal nocturnal hemoglobinuria (PNH), a rare and life-threatening condition in which the body’s immune system destroys the oxygen carrying red blood cells. Like existing treatments Soliris and Ultomiris, Empaveli works to inhibit the complement system, but it is the first therapy to targ...

In some diseases, such as lysosomal storage disorders, proteins are unable to serve their normal functions because they become misfolded. While some approaches, such as enzyme replacement therapies, have been used to treat these conditions, they can have significant limitations. Gain Therapeutics has developed a platform for using small molecule therapies to return proteins to their proper shape a...

Mouse models can play an essential role in allowing researchers to understand rare diseases and develop drugs to treat them. Cat Lutz, senior director of mouse repository and in vivo pharmacology genetic resource science at The Jackson Laboratory, researches mice as a model for human neurodegenerative disease. The lab’s mouse repository and Rare and Orphan Disease Center today features more than 1...

The recruitment of patients for rare disease clinical trials can be challenging because of issues such as small patient populations and their geographic dispersity, but the failure to take a patient-centric approach in designing trial protocols can add to the difficulties sponsors face in conducting such studies. The Center for Rare Diseases at PRA Health Sciences recently issued a toolkit focused...

The advent of genome editing is creating the potential to correct the underpinnings of genetic diseases by rewriting the mutations that cause them. Before these emerging technologies can be put to use to treat and cure genetic diseases broadly, a number of challenges must be overcome. These include such things as validating new gene editing technologies, finding ways to deliver them precisely to t...

PTC Therapeutics, through its partnership with the SMA Foundation and Genentech, won approval last year for Evrysdi, the first oral therapy for the rare neurodegenerative condition spinal muscular atrophy. Now, the SMA Foundation is working with the company to discover and develop regenerative treatments that can reverse the damage done by the disease. At the same time, the company is advancing it...

Chandler Crews was born with the rare, genetic condition achondroplasia, the most common form of dwarfism. In 2010, she decided to undergo a series of limb lengthening surgeries, which over a four-year period increased her height to 4’ 11” from 3’ 10.” We spoke to Crews, founder and president of the nonprofit patient organization The Chandler Project, about her experiences living with the conditio...

Children’s Mercy Research Institute has been expanding its efforts to understand the genetics underlying rare diseases. Earlier this year, it opened a new home in downtown Kansas City and at the end of last year launched Genomic Answers for Kids, a first of its kind pediatric data repository and the institutes flagship research initiative. We spoke to Tom Curran, senior vice president, chief scien...

Gene therapy is promising to provide treatments and potential cures for a long list of rare, genetic diseases. A key element of these therapies are the viral vectors that are used to deliver and insert the genetic material used to treat a patient. Guangping Gao, co-director of the Li Weibo Institute for Rare Diseases Research, director of the Horae Gene Therapy Center and Viral Vector Core, and pr...

Sanath Kumar Ramesh’s son Raghav was born with an ultra-rare and progressive disorder known as SSMD. The condition is caused by mutations in the GPX4 gene. There are only a handful of known patients with GPX4 mutations. In the past, most known cases resulted in death about a month after birth. Ramesh has moved with remarkable speed to find patients, raise money, and drive research. But he also rea...

In his new book, Emmy-winning news and documentary television producer Miguel Sancho recounts the efforts he and his wife Felicia Morton went through to get their son Sebastian diagnosed and treated for chronic granulomatous disease, a rare and deadly immunodeficiency. The book “More than You Can Handle: A Rare Disease, a Family in Crisis, and the Cutting-Edge Medicine that Cured the Incurable” fo...

The Innovative Genomics Institute; a partnership between the University of California, Berkeley and the University of California, San Francisco led by Nobel laureate Jennifer Doudna; is working to harness CRISPR-based genome editing to correct underlying mutations in monogenic diseases. The institute is initially focusing its efforts on sickle cell disease and a rare familial autoimmune disorder....

The economic burden of rare disease in the United States reached nearly $1 trillion in 2019, according to a new study from the Everylife Foundation for Rare Diseases. About 43 percent of that total is for direct medical costs. The balance includes such things as forced retirement, absenteeism, and presenteeism—the lost productivity of people who show up to work but are not fully functioning. We sp...

The ability to target the underlying cause of a disease and make a lasting correction makes gene therapy an attractive approach to treating neurodegenerative conditions. The advent of Zolgensma, a gene therapy for the treatment of the rare neurodegenerative condition spinal muscular atrophy, serves as a model for this approach. A recent review article in Nature Neuroscience looks at the advances i...

Poseida Therapeutics is perhaps best known for its immune-oncology cell therapy products, but the company’s platform technologies are also being used to develop a growing pipeline of gene therapy candidates. While the most advanced ones in its pipeline use viral vectors, newer candidates make use of a non-viral nanoparticle vector. This technology can increase the payload of the gene therapy, avoi...

Jazz Pharmaceuticals has been successful at building and commercializing a growing pipeline of therapies to treat rare neurologic conditions and hematologic cancers. Central to its strategy has been the use of acquisitions to build its pipeline. In fact, we should note that since recording this podcast, the company continued that approach with news that it would acquire GW Pharmaceuticals for $7.2...

CRISPR is a powerful editing tool, but it works best as a way to knock out genes rather than correct them. New approaches to gene editing, though, are providing the promise of more effective tools for addressing the underlying drivers of monogenic diseases. A recent study in Nature of an approach known as base editing in a mouse model of the ultra-rare genetic condition progeria, a disease that ca...

Arya Singh grew up with a child’s-eye-view of hospitals, operating rooms, and clinical trial sites. As someone with the rare and progressive neuromuscular disorder spinal muscular atrophy type 2, Singh knew what it meant to be isolated and frightened by both as a patient and a clinical trial participant. Now a student at Yale University with plans to pursue her interests in law and public policy i...