It’s a pivotal time for the field of gene therapy. A record number of treatments could be approved in the coming year, building on the more than ten currently approved therapies and increasing the momentum by which science transforms the lives of a growing number of rare disease patients. Although each rare disease affects fewer than 200,000 people, collectively there are more than 7,000 rare diseases that impact hundreds of millions.

Many of these rare diseases affect the cardiovascular system, constituting a significant public health problem worldwide. Currently, there is no approved gene therapy for any cardiac condition – but that could soon change. We’re working in close collaboration with the FDA and the EMA to advance a treatment for Danon disease, a devastating and fatal heart condition caused by mutations in the LAMP2 gene that impacts males and females who often die prematurely of their disease between the ages of 20 and 40. Right now, the only available treatment option is a heart transplant – which is not curative and often causes substantial lifelong complications.

Scientific innovators, including the biopharma industry, are rapidly pursuing potential one-time curative gene therapy treatments for genetic diseases like Danon disease. But to enable most rare disease patients to benefit from these advances, we must also devote concerted efforts to meaningfully enhance another crucial part of the patient experience – early diagnosis.

‘Although each rare disease affects fewer than 200,000 people, collectively there are more than 7,000 rare diseases that impact hundreds of millions’

It’s estimated that only 20% of people living with devastating genetic conditions receive a correct diagnosis. The other 80% are left not only without treatment options – but also without answers. For gene therapy to deliver on its fullest potential, the healthcare community must increase early, accurate diagnosis of potentially reversible or curative conditions through expanded genetic testing and newborn screening.

The path to an accurate diagnosis is often protracted and frustrating for those battling a rare disease. Rare diseases frequently cause seemingly unrelated symptoms, making them difficult to identify. And with thousands of rare diseases in existence, it’s impossible for medical professionals to understand them all in depth. The resulting burden for patients and their caregivers is immense, in the form of time, cost, travel and emotional distress, in addition to irreversible and potentially catastrophic disease impact.

It takes an average of five years for patients with rare diseases to receive a correct diagnosis, typically after three misdiagnoses and consults with five doctors. And these are just averages – for some, the journey is even more complex.

The United States’ (US) healthcare system relies too much on individual providers to make a diagnosis, instead of capitalising on methods such as screening or early genetic testing, which can provide more rapid and definitive answers. Approximately 80% of rare diseases have a genetic origin – which is why genetic testing is such a valuable diagnostic method. Identifying the root cause eliminates much of the guesswork and can lead to a prompt and accurate diagnosis.

Genetic testing has the potential to open new doors for rare disease patients. Identifying the underlying genetic cause can offer innumerable benefits to patients desperately seeking answers. Access to testing can reveal the root cause of patients’ symptoms, expedite the development of optimal care plans, and uncover certain research opportunities, including clinical trials and natural history studies. In the future, it may even allow the healthcare community to preventatively treat pre-symptomatic rare disease patients, when appropriate.

Genetic testing is a critical tool utilised by academic and biopharma groups to advance science and revolutionise treatment of rare diseases.

For patients, genetic testing is vital to accessing potentially transformative therapies. Yet, adoption of genetic testing has not increased at the same rate as clinical research.  Expanding what is included on genetic testing panels, increasing the speed at which they are completed and most importantly, elevating clinicians’ awareness of these panels and willingness to employ them as an essential diagnostic tool are all crucial components to enable scientific advances to transform patients’ lives.

Whole genome sequencing allows researchers to analyse for mutations and health indicators across the totality of a patient’s genes. Two main points of resistance to this method are cost and data management. Commercial pricing has decreased in recent years, but it’s still out of reach for many. Furthermore, interpreting and storing the resulting data can be a deterrent, given the personal nature of the information and lack of trust in healthcare systems’ judicious use of sensitive medical data.

For a healthcare provider with clinical suspicion of a genetic disorder, currently available targeted tests evaluate a panel of genes with known associations to specific diseases. They come at a reduced cost and lower data burden, which make them more feasible than broad genetic testing. But these panels cover only 1,700 of the 20,000 genes known to cause human disorders, so while they’re useful for detecting many conditions, countless rare diseases will inevitably fall between the diagnostic cracks.

To enable increased use of genetic testing, improved awareness and education around the benefits and necessity of testing are vital. There’s a pervasive sentiment that rare diseases are so uncommon that genetic testing is frequently unnecessary. Additionally, there are no available treatments for many of these diseases, so a precise diagnosis may not necessarily lead to a better outcome.

But the picture looks different when we step outside the individual experience and view the situation holistically. We see that hundreds of millions of people suffer from rare diseases.

And we realise that increased diagnosis demonstrates the severity of the unmet need.  This understanding could drive the development of new therapies – so untreatable conditions may one day become treatable. Importantly, and back at the individual level, even for diseases where available treatments are lacking, expert guidelines for optimal management are increasingly available and an accurate diagnosis enables not only participation in research but optimal supportive and palliative care.

Every parent wishes first and foremost for a healthy baby. But when that doesn’t occur, we know that early detection and treatment are the best options for patient and family health and well-being.

Each year in the US, roughly four million babies are screened for at least 31 serious disorders that can be detected at birth. Of those four million infants screened, over 12,000 newborns are found to have a disorder that, if left undiagnosed and untreated, would cause severe developmental disability or death.

‘For gene therapy to deliver on its fullest potential, the healthcare community must increase early, accurate diagnosis of potentially reversible or curative conditions through expanded genetic testing and newborn screening’

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

Currently, there is newborn screening for severe congenital heart defects, but this only covers a small number of heart diseases, leaving most rare and serious heart conditions undetectable at birth. It’s time to add additional diseases to these lists, including expanded screening for cardiac conditions.

Danon disease is a prime example to illustrate the immense impact of early and accurate diagnosis. In most boys and many girls, Danon disease manifests frequently during adolescence or very early adulthood, causes devastating symptoms and is ultimately fatal for patients. This rapid onset creates a limited window to catch and treat the disease effectively. And for some women, it may present only after having children, meaning the gene has already been passed on.

As a treatment for Danon disease advances toward potential commercialisation, it’s crucial that patients with the disease are identified as early as possible – and hopefully, one day, before symptoms even occur. Expanded genetic testing and screening for the disorder will give more patients the chance to access potentially life-changing treatment.

Danon disease is just one example, behind which are hundreds and possibly thousands of others. The pursuit of cures and transformative therapies could change not only individual lives, but our overall approach to managing serious disorders. To enable groundbreaking science to serve humankind, it is crucial that we focus not only on science, but on giving rare disease patients the answers they so desperately need – and a crucial part of this comes from early diagnosis and screening.

Jonathan Schwartz is Chief Gene Therapy Officer at Rocket Pharmaceuticals