RARECast

The Yaya Foundation recently achieved a milestone in advancing towards treatments for 4H leukodystrophy when it successfully developed a mouse model. It reflects a broader effort that has allowed the organization to drive towards the development of a gene therapy to treat the rare, neurodevelopmental. We spoke to Ron Garber, co-founder and board president of the Yaya Foundation, about 4H leukodystrophy, how the organization built a research agenda, and the rapid progress it has made.

In 2021, the U.S. Food and Drug Administration notified Stealth Biotherapeutics it would not consider its application seeking approval for elamipretide as a treatment for the ultra-rare mitochondrial disease Barth syndrome. The agency wants the company to produce evidence of the drug’s efficacy in a larger population of Barth syndrome patients than it studied, but the company believes it has exhausted the population in the United States of patients who fit the clinical trial criteria. Patients have lobbied the agency to give the drug a hearing, but there is growing concern that if the FDA fails to act, elamipretide will become unavailable to patients, who say the drug has given them the ability to lead a normal life. In an effort to move the FDA, Shelley Bowen, co-founder and director of family services for the Barth Syndrome Foundation, launched a Change.org petition calling on the agency to give a full and fair hearing to the drug. We spoke to Bowen about Barth syndrome, the fight over approval for the first drug to treat the condition, and why it points to a systemic problem with the lack of consistent use of the flexibility Congress granted the FDA to get treatments to patients with ultra-rare diseases. 

Scaling the production of biotherapeutics is challenging and requires more than just multiplying the ingredients in a recipe. That’s true for gene therapies as well where simply changing the nucleic acid of the payload can have dramatic effects on the product. Form Bio is seeking to address the challenges of making genetic medicines by leveraging AI to accelerate the development of cell and gene therapies. We spoke to Claire Aldridge, chief strategy officer for Form Bio, about the challenges of developing gene therapies, how Form’s AI platform can address that, and how it works grows out of tools that were developed to bring the woolly mammoth back from extinction.

Finding a diagnosis for a child with a rare condition can be challenging, even when his mother is a genetic counselor. Danielle Bonadies’ son Ethan was born with a brown birthmark known as a café au lait spot. But as the spots proliferated over the next few months, his pediatrician recognized it as a potential sign of a rare, genetic disorder. It wasn’t until Ethan was 2 that genetic testing led to a formal diagnosis of neurofibromatosis type 1, a genetic condition that leads the development of tumors that can affect the brain, nerves, and spinal cord. We spoke to Bonadies about caring for a child with neurofibromatosis, how her professional and private lives have been thrust together because of her son’s diagnosis, and her evolution as a patient advocate. 

Protein misfolding is an underlying issue for many diseases, including lysosomal storage disorders and some neurodegenerative conditions. When a protein misfolds, its three-dimensional structure is disrupted, and it can no longer function properly. Gain Therapeutics is using its AI-driven discovery platform to identify novel targets to fuel a pipeline of therapies that focus on enzymes involved in rare genetic diseases, but that also share genetic profiles with more prevalent ones. We spoke to Matthias Alder, CEO of Gain Therapeutics, about the role protein misfolding plays in a range of diseases, Gain’s platform technology, and its lead experimental therapy in development to treat Gaucher disease. 

Antibodies play an important role in the protective immune response. In some situations, though, such as autoimmune diseases, antibodies can cause harm by attacking healthy tissue. Hansa Biopharma has developed an antibody-cleaving enzyme technology platform to target pathogenic antibodies involved in autoimmune disease, organ transplantation, and gene therapies. Its lead experimental therapy, imlifidase, is designed to inactivate immunoglobulin G antibodies through a single intravenous treatment. It is in development for a range of rare, immunological conditions including Guillain-Barre syndrome or anti-GBM disease and as a pre-treatment for various gene therapies. We spoke to Matthew Shaulis, chief commercial officer and U.S. president for Hansa Biopharma, about the company’s antibody-cleaving platform technology, how it works, and its range of potential uses. 

Microglia are specialized immune cells in the central nervous system that act as sentinels to maintain healthy brain function. They protect the brain against processes that can ultimately lead to neurodegeneration. Vigil Neuroscience is developing precision medicines designed to target microglia and restore and enhance the performance of these cells when they fail to act as they should due to disease. The company’s lead program is in development as a treatment for ALSP, a rare, genetic, neurodegenerative condition. We spoke to Ivana Magovčević-Liebisch, president and CEO of Vigil Neuroscience, about the role of microglia, what happens to these cells in ALSP, and why the company’s approach can have implications for a range of rare and common neurodegenerative conditions.

Cystic fibrosis is a rare disease that has been an area of significant innovation. New therapies have provided life-changing treatments for most patients, but about 10 percent of people with the condition don’t benefit from these treatments because of the specific mutations underlying their condition. We spoke to Jamie Chang, senior medical director at the contract research organization Rho, about the advances that have been made to treat cystic fibrosis, the treatment gap that remains, and what’s working its way through the pipeline that may change that.

At 41, Bill Potts received a diagnosis of thyroid cancer. He listened to the recommendations from his primary care physician and didn’t seek out a second opinion. It was only six months later, during a follow up visit when his doctors wanted to repeat his treatment with radioactive iodine that he began to ask questions and started to advocate for himself. He now says he would likely be dead had he not sought out a second opinion at that time. He’s since learned a lot about advocating for himself with cancer as he’s been diagnosed six times with cancer. He’s taken what he’s learned from his experiences and written Up for the Fight, a guide for newly diagnosed cancer patients, family members, and caregivers. It provides not only critical advice on dealing with the mental aspects of the disease, but also lots of practical advice about navigating the healthcare system, insurance companies, and treatments that could only come from lived experience. We spoke to Potts about why it’s essential for patients to learn to advocate for themselves, how to navigate the mental and emotional aspects of the disease, and why it’s important to stay motivated and celebrate small achievements along the way.

Regulatory T cells target systemic inflammation and neuroinflammation, but when they fail to function properly, they can drive serious health conditions including neurodegenerative, metabolic, and autoimmune diseases. Coya Therapeutics is developing a pipeline of therapies designed to restore the ability of Tregs to modulate the immune system and reduce inflammation. The company’s lead experimental therapy is a combination of two biologics designed to treat ALS by boosting anti-inflammatory Tregs while suppressing other immune cells that drive inflammation. We spoke to Howard Berman, chairman and CEO of Coya, about the role of inflammation in neurodegenerative conditions, Tregs, and the company’s experimental therapy to treat ALS.

Cristóbal Baca and Ana Ortiz came to New Mexico in 1600. Today, they have as many as 5 million descendants. A four-year effort involving community volunteers and workers, medical professionals, researchers, and families across New Mexico unraveled what had been a long-standing medical mystery. It turns out Baca and Ortiz are the source of a founder mutation for cerebral cavernous malformation, a sometimes-hereditary illness that causes the development of abnormal blood vessels in the brain and spinal cord and is potentially fatal. Some 30,000 New Mexicans carry the mutation. We spoke to Connie Lee, president and CEO of the Alliance to Cure Cavernous Malformation, about the Baca Family Historical Project, how her organization leveraged partnerships with community leaders to identify people with the condition, and how the organization used a novel approach to engage people and improve their access to testing and care.

In June, the National Institutes of Health’s National Institute of Neurological Disorders and Stroke made a five-year, $22.8 million grant to a group led by The Jackson Laboratory to develop gene-editing therapies for four rare, neurological conditions. The use of a platform approach to develop therapies for multiple indications follows other efforts on going at the National Institutes of Health in the area of gene therapies. We spoke to Steve Murray, associate professor at The Jackson Laboratory, about the promise of gene-editing, the work being done under the grant, and why the work could have broad implications for treating rare genetic neurological conditions.

CDKL5 deficiency disorder (CDD) is a serious and rare, genetic condition characterized by early onset and difficult to control seizures, as well as severe neuro developmental impairment. Last year, the U.S. Food and Drug Administration approved Marinus Pharmaceuticals Ztalmy to treat seizures associated with CDD, the first FDA approved therapy for the condition. Marinus is seeking to expand the use of Ztalmy in other seizure disorders including tuberous sclerosis complex and Lennox-Gastaut syndrome. We spoke to Alex Aimetti, chief scientific officer of Marinus, about Ztalmy, how it works, and the efforts to expand its use to other seizure disorders.

Clothing is both functional and a means of self-expression, according to Open Style Lab, a nonprofit that works with designers, engineers, and occupational therapists to create clothing that addresses the needs of people with disabilities. In September 2022, as part of Genentech’s SMA My Way initiative, Open Style Lab and the SMA community joined forces for New York’s Fashion Week to feature the Double-Take fashion show in the hopes of increasing the visibility of people with disabilities and championing adaptive fashion. We spoke to Yasmin Keats, executive director of Open Style Lab, about her organization’s efforts to promote the design of adaptive fashion, the impact it can have on work and other opportunities for people living with disabilities, and how it is helping to change the fashion industry.

Pulmonary arterial hypertension is a rare and progressive condition characterized by high blood pressure in the arteries of the lungs due to their narrowing or a blockage. This causes the heart to work harder to pump blood and leads to heart failure, the need for lung transplantation, and death. Aerami is developing an inhaled form of the targeted cancer therapy imatinib as a treatment for PAH. We spoke to Josh Ziel, chief operating officer and interim CEO of Aerami, about pulmonary arterial hypertension, the company’s experimental therapy to treat the condition, and its efforts to build a pipeline of therapies that make use of its proprietary inhalation technology.

The search for a diagnosis can take many years and requires going from doctor to doctor without finding a definitive answer for people with ultra-rare conditions, atypical presentations, or yet-to-be discovered diseases. A group of undiagnosed and ultra-rare diseases patients and their family members, medical providers, and advocacy partners launched the Undiagnosed Diseases Network Foundation to improve access to diagnosis, research, and care for people with undiagnosed diseases. We spoke to Amy Gray, CEO of the UDNF, about its work, its relationship with the National Institutes of Health-backed Undiagnosed Disease Network, and the organization’s top priorities.

Patients may be the experts on their own conditions, but data that captures health-related quality of life is often underutilized in research. The PKD Foundation is working with IQVIA to create a registry of patients with autosomal dominant polycystic kidney disease, a rare kidney condition. The ADPKD registry focuses on patient-reported, health-related quality of life data. The organization believes the registry will not only provide new insights into the condition but help with the design of efficient clinical trials and accelerate the development of new treatments. We spoke to President and CEO of the PKD Foundation Susan Bushnell, Vice President of Research Programs at PKD Foundation Elise Hoover, and Senior Director of Global Strategic Planning for IQVIA’s Integrated Health Practice David Voccola, about the new registry, how it is leveraging technology to enable patients to drive insights into their condition, and the challenges it needs to overcome.

Mary Morlino knows what it’s like to search for information and resources for a loved one with a rare disease or yourself. She had two nephews who were diagnosed with the rare neuromuscular disease Becker muscular dystrophy and later she was diagnosed with the rare autoimmune condition sarcoidosis. She now performs that search for information and resources professionally, so others don’t have to do so. Today, Morlino serves as Global Genes’ RARE Concierge Patient Services manager. The service serves as an entry point for patients, caregivers, patient advocates, and other rare disease stakeholders in search of information, resources, and connections. We spoke to Morlino about her own rare disease journey, the work she’s doing as part of Global Genes’ RARE Concierge program, and the need she is addressing.

Our interactions with the environment can have unexpected effects on our genes and trigger a biologic response that leads to the onset of disease. These interactions can also leave a measurable record in what’s referred to as the exposome. LinusBio, which emerged from the exposome laboratory at Mount Sinai Health System, has developed a test for autism that relies on analyzing a single strand of hair. The company said the test is capable of diagnosing autism at birth. We spoke to Manish Arora, founder and CEO of LinusBio, about the exposome, how the company’s test for autism works, and how this opens the potential for early interventions.

Congenital pseudarthrosis of the tibia is a rare condition that can cause spontaneous fractures, mobility problems, and impede proper growth. It is treated surgically, but because the bone often breaks again, it can lead to amputation. Novadip is developing an autologous cell therapy to allow tissue regeneration of large bone defects. We spoke to Denis Dufrane, co-founder and CEO of Novadip, about the rare pediatric bone disorder, the company’s cell therapy to address the condition, and how it works.