Rare Disease Day 2025: Rounding up the latest advancements in research and treatment

About 300 million people around the world—and around 1 in 10 U.S. citizens—live with a rare disease. Representing over 6,000 various disorders and conditions, the impact of rare diseases extends even beyond the patients themselves to their families, caregivers, medical teams, and communities.

On Rare Disease Day, we join the global community in raising awareness around rare diseases and promoting social and healthcare equity for the people living with these conditions. Lack of scientific understanding and public awareness both contribute to challenges for patients and their providers.

In the year since Rare Disease Day 2024 (observed on the rarest of all days, February 29), the scientific community has made promising advancements in the treatment of rare conditions like cystic fibrosis, Huntington’s disease, muscular dystrophy, and sickle cell disease.

Let’s take a look at some of the most noteworthy updates in rare disease research and treatment.

Gene and cell therapy breakthroughs in cystic fibrosis

Cystic fibrosis (CF) is a genetic disease that causes mucus in the body to become thick and sticky, leading to inflammation, infections, and other issues in the lungs, pancreas, and other organs. For the over 100,000 people living with cystic fibrosis worldwide, managing the disease often requires a daily regimen of airway clearance, inhaled medication, and various other therapies.

The last decade saw the rise of new medications that modulate the cystic fibrosis transmembrane regulator (CFTR) gene, helping certain patients regain near-normal lung function and life expectancy.

But current CFTR modulators only work on patients with specific genetic mutations. Because these gene variants are less common in people of non-European descent, many populations with existing health disparities are less likely to benefit from CFTR modulation.

But advancements in gene therapy could change that. In 2024, researchers from the University of Iowa and the Broad Institute optimized a form of gene therapy called prime editing, which enables the replacement of any letter in the genetic code. While there are more than 2,000 variants of the CFTR gene, prime editing could enable providers to treat any of them with equal efficacy.

The biggest obstacle for prime editing—and any form of gene therapy—is in delivering the treatment to the right cells. Researchers at Mass General Brigham are employing gene therapy alongside cell therapy, in which cells from the patient or donor are removed and modified in a lab before being returned via infusion. And in Europe, biopharmaceutical developer Boehringer Ingelheim just launched the first human trials of its inhaled gene therapy treatment for cystic fibrosis.

Overall, 2025 is shaping up to be a good year for CF researchers seeking alternative treatment pathways. A recent study from Case Western University found that melatonin treatment improved bacterial clearance and inflammation in mice with CF. Plus, Dartmouth researchers learned that cystic fibrosis impacts the gut microbiomes of infants, suggesting that probiotics or dietary interventions could mitigate the effects of the disease.

New avenues for treatment of Huntington’s disease

Like cystic fibrosis, Huntington’s disease (HD) is a progressive disorder caused by the mutation of a gene (the huntingtin, or HTT gene, on chromosome 4). But unlike CF, Huntington’s disease primarily affects the brain, causing long-term neurodegenerative effects on mobility, cognition, and psychiatric health.

Both diseases have another thing in common: They currently have no cure. But that could be changing, thanks to recent advancements in HD research.

A team of UK and U.S.-based scientists identified a DNA repair protein that causes the expansion of problematic genetic code in people with Huntington’s disease. By targeting this protein with antisense oligonucleotides (lab-made molecules that attach to mRNA), providers can reduce the expansion of the cytosine-adenine-guanine (CAG) repeats that tend to correlate with the severity of HD.

Harvard and MIT researchers furthered the understanding of this process with a new study that shows how CAG sequences tend to slowly build over decades in patients’ brain cells, before rapidly expanding and causing cell death. This discovery helps to explain why HD symptoms tend to manifest around middle age, despite the mutation being present at birth.

A UC-Irvine led team shed even more light on the mechanisms of Huntington’s disease by uncovering how CAG repeats affect key regulators of RNA processing, the protein TDP-43 and the m6A RNA modification. Not only are these mechanisms central to the relationship between HD and defective RNA processing; they’re also associated with other neurological disorders, and may present valuable targets for therapies targeting a wide range of diseases.

While a cure has yet to fully materialize, there’s more good news for HD treatment and management: A Spanish study published in Scientific Reports found that a cognitively active lifestyle could help HD patients maintain motor and brain function longer. And University of Iowa researchers recently discovered that widely available beta-blockers (used commonly to treat heart conditions) could slow the onset and worsening of HD symptoms.

Groundbreaking firsts in the treatment of muscular dystrophy

Muscular dystrophy (MD) comes in dozens of varieties with varying symptoms, prognoses, and areas of impact. Caused by mutations in the genes responsible for muscle development and function, different forms of MD manifest at different ages and in different parts of the body, but all forms tend to ultimately lead to failure of critical organs like the heart and lungs.

The most effective MD treatments to date involve the administration of genetic therapies to newborns to modify the genes related to spinal muscular atrophy. But in 2021, researchers made the groundbreaking decision to treat a fetus for MD while still in the womb.

In early 2025, those researchers published the results of their study, revealing that the patient had grown into a healthy two-and-a-half-year-old girl with no signs of the disease. While the child continues to take the gene-targeting drug, her current condition could give hope to would-be parents concerned about passing on the disease.

The release of the study coincides with the FDA’s decision to lift a two-year hold on Entrada Therapeutics’ MD candidate drug. With the go-ahead from the federal government, Entrada can now test the drug on patients with MD in the U.S. (it had previously studied the drug’s impact on healthy patients in the UK). Likewise, an MD drug from Cumberland Pharmaceuticals scored a similar win this year, hitting its goals during phase 2 trials.

As with other rare diseases, identifying new treatment pathways is a top concern in MD research—and there’s good news here, too. German researchers recently uncovered a mechanism that upregulates utrophin, a protein that could compensate for dystrophin deficiency in certain muscular dystrophy patients.

CRISPR could cut down sickle cell disease

Sickle cell disease (SCD) causes blood cells to develop a rigid, inflexible shape, impacting their ability to move through blood vessels and leading to painful episodes, chronic fatigue, and even organ damage and failure.

In December 2023, the FDA approved the gene therapies Casgevy and Lyfgenia, establishing the possibility of long-term relief (if not an outright cure) for SCD patients. While these treatments are revolutionary in their potential, they are incredibly resource intensive, requiring blood transfusions, stem cell transplants, and chemotherapy that occurs over a series of months. Patients must be 12 years or older and have access to advanced medical facilities capable of delivering the $1.2 million treatment.

However, new research from the University of California San Francisco could open the door for many patients previously deemed unsuitable for treatment. Published in November 2024, the UCSF study explores the use of CRISPR technology to edit a patient’s own blood cells and return them through a bone marrow transplant. Ideally, the “corrected” stem cells proliferate and produce normal, disc-shaped blood cells.

Researchers say the new therapy is safer than a standard stem cell transplant and eliminates the need for a suitable donor. Furthermore, it could allow patients to begin receiving treatments at younger ages.

Find the providers, therapies, and patients involved in rare disease treatment

The latest advancements in rare disease research and treatment highlight some incredible progress. From gene therapies to repurposed drugs to alternative treatment pathways, the medical and scientific community has come a long way in addressing rare diseases—even since the first Rare Disease Day was observed in 2008.

Whether you’re interested in helping providers bridge the knowledge gap in rare diseases, want to find the physicians responsible for treating specific patient cohorts, or need to understand how rare disease impacts your market, Definitive Healthcare can help.

Our healthcare data and analytics solutions help you navigate the healthcare landscape, make more effective strategic decisions, and seize the most impactful opportunities. Sign up for a free trial today to learn more.