Realizing the full potential of gene therapy through increased genetic testing

This is a critical moment in the field of gene therapy. A record number of treatments could be approved next year, adding to the more than a dozen currently approved, adding to science’s drive to transform the lives of a growing number of people with rare diseases. While each rare disease affects fewer than 200,000 people, there are more than 7,000 rare diseases in total affecting hundreds of millions of people.

Many rare diseases affect the cardiovascular system and constitute a major global public health issue. Currently, no gene therapies have been approved for any heart disease, but that may soon change. We are working closely with the FDA and EMA to advance treatments for Danon disease, a devastating and fatal heart disease caused by mutations in the LAMP2 gene that affects both men and women, who often die prematurely from the disease, often between the ages of 2 and 2. 20 and 40. Currently, the only available treatment option is a heart transplant, which has no cure and often results in serious, lifelong complications.

Scientific innovators, including those in the biopharmaceutical industry, are rapidly pursuing potential one-time gene treatments for genetic diseases such as Danon disease. But in order for the majority of rare disease patients to benefit from these advances, we must also work together to actually enhance another key part of the patient experience—early diagnosis.

It is estimated that only 20% of people with devastating genetic diseases receive a correct diagnosis. The other 80% not only have no treatment options, they also have no answers. To realize the full potential of gene therapy, the healthcare community must increase early, accurate diagnosis of potentially reversible or curable conditions through expanded genetic testing and newborn screening.

Delays and opportunities in rare disease diagnosis
For those battling rare diseases, the process of accurate diagnosis is often long and frustrating. Rare diseases often cause seemingly unrelated symptoms, making them difficult to identify. Because there are thousands of rare diseases, it is impossible for medical professionals to understand them in detail. The resulting burden on patients and their caregivers includes time, expense, travel, and emotional distress, as well as irreversible and potentially catastrophic disease effects.

Rare disease patients take an average of five years to receive a correct diagnosis, often after three misdiagnoses and five doctor consultations. These are just averages—for some, the journey is even more complicated.

The U.S. health care system relies too much on individual providers to make diagnoses, rather than utilizing methods like screening or early genetic testing that can provide faster, more definitive answers. About 80% of rare diseases have a genetic origin, which is why genetic testing is such a valuable diagnostic method. Determining the root cause eliminates much of the guesswork and allows for a timely, accurate diagnosis.

Genetic testing has the potential to open new doors for patients with rare diseases. Identifying the underlying genetic cause can bring countless benefits to patients desperate for answers. Access to testing can reveal the root cause of a patient’s symptoms, expedite the development of the best care plan, and identify certain research opportunities, including clinical trials and natural history studies. In the future, it may even allow the healthcare community to administer preventive treatments to patients with rare diseases who develop symptoms when appropriate.

Genetic testing: Expanding scope enables early diagnosis
Genetic testing is an important tool used by the academic and biopharmaceutical communities to advance science and revolutionize treatment of rare diseases.

For patients, genetic testing is critical to accessing potentially transformative treatments. However, adoption of genetic testing has not grown at the same rate as clinical research. Expanding the content of genetic testing panels, increasing the speed of completion, and most importantly, increasing clinicians’ awareness of these panels and their willingness to use them as essential diagnostic tools are key components in enabling scientific advances to transform patient health. . Life.

Whole-genome sequencing allows researchers to analyze a patient’s entire gene for mutations and indicators of health. The two main points of resistance to this approach are cost and data management. Commercial pricing has declined in recent years but remains out of reach for many. Furthermore, interpreting and storing outcome data can be a deterrent given the personal nature of the information and the lack of trust in the healthcare system to use sensitive medical data wisely.

For health care providers who clinically suspect a genetic disorder, currently available targeted tests evaluate a panel of genes known to be associated with a specific disease. Their lower cost and lower data burden make them more feasible than widespread genetic testing. But these panels cover only 1,700 of the 20,000 genes known to cause human disease, so while they can be used to detect many diseases, countless rare diseases will inevitably fall through the diagnostic cracks.

To increase the use of genetic testing, increasing awareness and education about the benefits and necessity of testing is critical. Rare diseases are generally thought to be so rare that genetic testing is often unnecessary. Additionally, there are no treatments available for many of these diseases, so an accurate diagnosis does not necessarily lead to better outcomes.

But things look different when we look beyond our personal experiences and look at the situation holistically. We see hundreds of millions of people living with rare diseases.

We recognize that the increase in diagnoses demonstrates the severity of the unmet need. This understanding could lead to the development of new treatments – so untreatable conditions may one day become treatable. Importantly, returning to the individual level, expert guidance on optimal management is increasingly available even for conditions that lack available treatments, and an accurate diagnosis can not only engage in research but also provide optimal support and palliative care protect.

Newborn Screening: A Life-Changing Start
Every parent wants first and foremost to have a healthy baby. But when that doesn’t happen, we know that early detection and treatment are the best options for the health and well-being of patients and their families.

In the United States, approximately 4 million babies are screened each year for at least 31 serious diseases that can be detected at birth. Of the 4 million babies screened, more than 12,000 were found to have a condition that, if not promptly diagnosed and treated, will result in severe developmental disabilities or death.

The Recommended Uniform Screening Panel (RUSP) is the national guideline for newborn screening, but it is ultimately up to each state to determine requirements. Most screen for diseases on RUSP, but only some screen for other diseases.

Currently, there is newborn screening for severe congenital heart disease, but this only covers a small number of heart diseases, and most rare and serious heart diseases are undetectable at birth. It’s time to add more diseases to these lists, including expanding screening for heart disease.

Demonstrating impact through Danon disease
Danon disease is a prime example of the huge impact of early and accurate diagnosis. In most boys and many girls, Danon disease often presents during adolescence or early adulthood, causing devastating symptoms that are ultimately fatal to the patient. This rapid onset creates a limited window for effective detection and treatment of the disease. For some women, it may only appear after giving birth, meaning the gene has been passed on.

As treatments for Danon disease move toward potential commercialization, it is critical to identify patients with the disease as early as possible – and hopefully one day, before symptoms appear. Expanding genetic testing and screening for the disease will give more patients access to potentially life-changing treatments.

Danon disease is just one example, there are hundreds if not thousands of other diseases. The pursuit of cures and transformative treatments can not only change individual lives, but also our overall approach to treating serious illnesses. In order for groundbreaking science to serve humanity, it’s critical that we focus not just on the science, but on giving patients with rare diseases the answers they desperately need, and a critical part of that comes from early diagnosis and screening .