Rarecast

Pediatric and primary hyperoxaluria is a rare genetic condition that causes over absorption of oxalate, a compound found in many foods. Too much oxalate can lead to the formation of kidney stones and cause progressive damage of the kidneys. Allena Pharmaceuticals is developing an oral enzyme to treat both the rare form of hyperoxaluria and a more common form of the condition. We spoke to Louis Brenner, CEO of Allena, about the company’s experimental therapy to treat hyperoxaluria, it’s platform for delivering enzymes orally, and the potential to apply the technology beyond kidney diseases.

Casimir Trials is a contract research organization that is seeking to bring patient and caregiver perspective into the clinical trials process. It’s working with drug developers to create endpoints and measures that can provide rigorous and quantifiable means of demonstrating whether an experimental therapy provides meaningful improvements to a patient’s quality of life. We spoke to Christine McSherry, co-founder and CEO of Casimir Trials, about the challenges of developing patient-centric outcome measures, how technology is allowing for the capture of real-world evidence, and how Casimir began with a challenge from the FDA’s Center for Drug Evaluation and Research Director Janet Woodcock to a mother and patient advocate concerned over the use of endpoints that could obscure the value of needed drugs to rare disease patients.

Idiopathic pulmonary fibrosis is a serious, life-limiting lung disease characterized by fibrosis and scarring of lung tissue. Patients generally live only about three to five years after a diagnosis. Approved therapies can slow down the progression of the disease, but no available therapies halt or reverse it. The only curative therapy is a lung transplant, an option that is available to only a small subset of patients. Promedior is developing an experimental therapy it believes may not only halt the disease, but reverse it. We spoke to Jason Lettmann, CEO of Promedior, about the company’s experimental therapy, how it works, and why it may have the potential to treat a wide range of fibrotic diseases.

Patients with rare diseases often have a complex constellation of symptoms that require the care of multiple specialists. Getting access to the needed mix of physicians and counselors can represent geographic and scheduling challenges for patients and caregivers and create difficulties in coordinating care between specialists. One approach to addressing these needs has been the development of centers of excellence that can provide comprehensive and coordinated care for patients with experts in their condition. We spoke to Amber McCarthy, a Huntington’s disease social worker with UTHealth/UT Physicians in Houston, about the Huntington’s Disease Society of America’s Centers of Excellence, how these centers operate, and how they are transforming care for Huntington’s disease patients.

Mitochondria are the powerhouses of the cell and play a central role in a number of rare diseases. Mitochondria have their own DNA and Minovia Therapeutics is seeking to develop cell therapies designed to repair damaged mitochondrial DNA using autologous stem cells that have been enriched with blood-derived mitochondria. We spoke to Natalie Yivgi Ohana, co-founder and CEO of Minovia, about the company’s mitochondria augmentation therapy, how it works, and why it may point the way for treating more common conditions, such as Alzheimer’s disease.

Earlier this year Passage Bio announced its launch with $115.5 million in funding and a group of founders with a strong pedigree. The company’s founders include gene therapy pioneer James Wilson, pharmaceutical industry veteran Tachi Yamada, and former Alexion executive and OrbiMed Venture Partner Stephen Squinto. One point of distinction for the company is its unique partnership with the University of Pennsylvania and its Gene Therapy Program, which gives it access to technology developed there, as well as its preclinical translational science capabilities. We spoke Squinto, interim CEO of Passage Bio, about the company’s focus on rare monogenic CNS diseases, its relationship with Penn, and why he’s confident with strong data, discussion with payers will not be a problem.

AGTC is developing gene therapies to treat patients with rare inherited eye conditions. It has multiple programs it is advancing to restore visual function in patients with diseases that threaten to leave them blind. One issue that has emerged, though, is finding the right measures and endpoint for its clinical studies and getting the U.S. Food and Drug Administration to recognize the traditional endpoints and measures used for eye diseases may not be well suited for all of these conditions. We spoke to Sue Washer, CEO of AGTC, about the company, the indications it is pursuing, and its efforts to find and use more appropriate endpoints for its studies.

Avidity Biosciences is pioneering antibody oligonucleotide, a new class of therapeutics that marry the target selectivity of monoclonal antibodies with the precision of genetic medicine. The company is focusing on treatments for rare muscle disorders including myotonic dystrophy type 1 and Duchenne muscular dystrophy. We spoke to Art Levin, executive vice president of research and development at Avidity Biosciences, about the company’s therapeutic approach, why it’s focusing on rare muscle disorders, and the path forward for its therapies.

Global Genes Rare University is rolling out a new online course aimed at helping rare disease patients and families understand the world of genetics. The course, which is free, starts with the basic genetic concepts for rare disease, and them moves to family and heredity, genetic testing, and scientific advances. We spoke to Holly Snyder, a lead editor on the Rare University genetics course and senior genetic counselor at Illumina, about what rare disease patients and their families should understand about genetics, genetic testing, and why genetic literacy matters.

For rare disease patient groups seeking to drive research toward the development of therapies, many obstacles exist. By setting an overarching research agenda, driving collaborations among researchers, and sharing what is learned, patient groups are getting the most out of limited budgets and accelerating the time it takes to develop new treatments. The newly announced Rare As One Project from the Chan Zuckerberg Initiative seeks to help rare disease patient organizations apply the collaborative research model and improve on it. We spoke to Tania Simoncelli, science policy director of the Chan Zuckerberg Initiative, about the program, how it works, and what the organization hopes the long-term effects of its efforts will be.

Wendy Chung and her lab have proven a talent for identifying new rare diseases. She and her team have discovered more than 44 genetic conditions to date. But Chung, a professor of pediatrics and medicine at Columbia University and New York-Presbyterian Hospital, and director of the clinical genetics program at Columbia University, is driving beyond discovery to help patients find therapeutic alternatives for these conditions at Columbia University’s Center for Rare Pediatric Genetic Diseases. We spoke to Chung about the Center, how it works to find new treatments for rare diseases, and what hopes she has for scaling and accelerating the search for new therapies treat rare diseases with small populations.

The emotional impact a rare disease can have on siblings of children with these conditions can be significant. A sibling voices survey evaluating the psychological effects of growing up with a sibling with severe epileptic encephalopathies presented at the European Congress on Epileptology last year suggests these children may be as risk for anxiety or depression. We spoke to Lauren Schwartz, a psychologist at the Rehabilitation Medicine Clinic at UW Medical Center, about the study, what it found, and what parents should take away from it.

Early diagnosis and intervention can improve outcomes for children with autism spectrum disorder but arriving at a diagnosis can be difficult at an early age. To diagnose the condition, doctors have relied on behavioral tests and the average age of diagnosis in the United States is more than 4 years. NeuroPointDX has developed a diagnostic test that looks at metabolic imbalances in the blood that can diagnose a child with the condition as young as 18 months. We spoke to Elizabeth Donley, CEO of Stemina Biomarker Discovery and NeuroPointDX, about the condition, how the company’s test works, and what it might suggest about the biology of the condition.

Natural history studies track the course of a disease over time, helping researchers understand the different ways a condition may manifest itself and progress. These studies can also provide insight into whether patient populations should be divided into subtypes for more targeted therapeutic approaches. Such data often represents a foundational understanding of a disease that can play an essential role in the design of clinical trials, helping investigators determine appropriate protocols and select endpoints for a study. In some cases, natural history studies can serve as an alternative to a placebo arms of a clinical trial. Ahead of the upcoming Rare Drug Development Symposium, we spoke to Erika De Boever, deputy director of the Orphan Disease Center at the University of Pennsylvania School of Medicine, about natural history studies, the different types that exist, and why they play such a critical role in clinical trials for rare diseases.

When Lara Pullen’s son was diagnosed with Prader-Willi syndrome, she began to dive into the scientific literature about the rare condition. Pullen, a scientist and co-founder of the Chion Foundation, discovered that pitolisant, a recently approved drug for narcolepsy, might benefit patients with Prader-Willi. Working with her Chion co-founder Maria Picone, who developed an online data-gathering platform for patient-reported outcomes, they tracked the effects of the drug in three patients. In a clinical vignette published in the Journal of Pediatric Pharmacology and Therapeutics in April, they reported their findings. We spoke to Pullen about her efforts, the value of patient-reported outcomes, and why the work she’s done suggests the need for a more neurologically-based approach to treating Prader-Willi.

One reason for the extended diagnostic odyssey that rare disease patients face is that doctors are often unfamiliar with the rare conditions they may have. In addition, doctors are trained to think of the likeliest explanation for a patient’s symptoms, which may be similar to those of more common diseases. London-based Mendelian is working to bring machine learning to the rare disease diagnostic process as a way to identify patients whose symptoms may suggest they have an underlying rare genetic disease and provide a path forward to finding an answer. We spoke to Rudy Benfredj, co-founder and CEO of Mendelian, about the diagnostic challenge rare disease patients face, the company’s platform technology, and whether he thinks we’ll see an end to the diagnostic odyssey anytime soon.

Children awaiting adoption with a rare disease may go untreated or receive minimal treatment. If they go unplaced, they may face life in a long-term care facility, or nursing home. Gift of Adoption is a nonprofit that provides adoption assistance grants to help vulnerable children find a permanent home and the chance to thrive. We spoke to Pam Devereux, CEO of Gift of Adoption, about the cost of adoption, how her organization works, and the need it is seeking to address.

April 29 is Undiagnosed Rare Disease Day. It is a day when advocates raise awareness among the general public and policy makers about the emotional, physical, and financial impact living with an undiagnosed rare disease has on patients and their families. Ahead of this year’s Undiagnosed Rare Disease Day we spoke with Ava Szajnuk, an 11-year-old undiagnosed rare disease patient and advocate, about how her condition impacts her daily life, and the work she’s done as an advocate.

The Foundation for Angelman Syndrome Therapeutics Australia says it has created a Global Angelman Syndrome Registry that gives parents and caregivers the power to drive the collection of data. Its goal is to make the registry the largest collection of information about the neurological disorder to date and use it to inform the research for new therapies by providing insights into the developmental progress, medication, and seizure management related to the condition. One unique aspect of the registry is that it uses an open-source framework developed by Centre for Comparative Genomics at Murdoch University in Perth, Australia. We spoke to Meagan Cross, chairperson of the Foundation for Angelman Syndrome Therapeutics Australia, about Angelman syndrome, the efforts to build the registry, and why the use of an open-source platform can help address barriers rare disease organization face in creating registries.

Rett syndrome is a genetic disorder that mostly affect girls and is often misdiagnosed as autism, cerebral palsy, or non-specific developmental delay. A study recently published in the journal Neurology reports encouraging results from a mid-stage clinical trial for an experimental therapy to treat the condition. The patient organization Rettsyndrome.org played a key role in identifying the potential application for the drug in Rett syndrome and provided early funding. We spoke to Steve Kaminsky, chief science officer of Rettsyndrome.org about the drug, the role his organization has played in its development, and how it may one day change the landscape for patients with the condition.