Guest Column | December 7, 2020

Reflecting On The Meaning Of Our Work In Gene Therapy

By Andrea Spezzi, M.D., Chief Medical Officer, Orchard Therapeutics


For so many of us in the cell and gene therapy industry, we entered this field because we were deeply motivated by the life-changing potential such therapies, if approved, could have for patients, and by extension, their families, and communities. This is especially true for gene therapies that aim to treat rare diseases given the fact that so few rare diseases have any approved treatment options available.

Certainly, this was the case for me. Since childhood, I dreamt of becoming a pediatrician, and I dove head-first into my medical training and subsequent fellowship in pediatric immunology. Over the next 12 years, I practiced medicine in Argentina, Spain, and eventually the UK, working with children suffering from rare, often life-threatening immune deficiencies. I saw first-hand how expert medical management could improve outcomes for some children, but I still struggled to come to terms with the fact that there were many children I couldn’t help. Even when treatments exist, such as a bone marrow transplant, they are not available or accessible to all patients. Too often, I found myself talking with desperate parents without optimal medical or treatment options for their child. 

I wanted more for these children and their families. I began to feel that I might serve them better by focusing more upstream, applying my learnings and experiences as a physician to developing the treatment options that could help solve the challenges I’d observed. With this realization, I pivoted my energy to work in drug development, even returning to university to earn a degree as a pharmaceutical physician.

As luck would have it, I entered the field at a time of unprecedented new scientific and medical promise, particularly in the development of therapies for rare genetic diseases. Early clinical trials were indicating that gene therapy could be a viable treatment for the kinds of immunological diseases I’d treated in the clinic.

It would take another few years, but my career path would eventually intersect with this nascent field of gene therapy. In 2010, I began work in GSK’s rare disease unit on the clinical development of the hematopoietic stem cell (HSC) gene therapies that would eventually form the foundation of Orchard’s pipeline — including programs for metachromatic leukodystrophy (MLD), Wiskott Aldrich syndrome (WAS) and Hurler syndrome (MPS-I). The work was incredibly exciting and fulfilling. I knew at that point that I had found my path toward contributing to treatments for patients with rare diseases where current treatment options were limited or did not exist.

Today, as Orchard’s chief medical officer, it’s thrilling to see that we’re further along this path than ever before. Though I have fewer opportunities to meet and speak with patients and families than I did in my pediatric practice, the opportunities I do have are incredibly precious. However, I will never forget the families I sat alongside in times of intense pain as they mourned the loss of a child. This is what continues to be my driving force each day as we work to develop potentially transformative treatments for the patients and families affected by these devastating diseases.

Many rare genetic diseases are not part of standard genetic screening at birth; and some also have rather vague, non-specific symptoms that could be attributed to other more common developmental delays. As a result, families often do not receive a definitive diagnosis for their child’s condition until his or her disease is quite progressed. I’ve known of families who are experiencing the agony of watching an older sibling succumb to disease while a younger sibling is being tested and treated thanks to the early diagnosis made possible by a sister or brother. This dynamic keeps us constantly mindful of what’s at stake in our efforts to treat young patients with these horrific diseases.

Still, as I did earlier in my career, I continue to focus on how we can solve these upstream problems. My medical background has given me greater insights into the patient journey as it stands today, as well as the many continued opportunities for improvement. I’ve come to understand that earlier diagnosis of rare genetic diseases is much more likely when included as part of the standard newborn genetic screening panels administered by national and local governments. As a result, we at Orchard have been working alongside advocacy groups and clinicians in both the U.S. and Europe to advance disease education and awareness; support the development and testing of appropriate and validated diagnostic assays, and advocate the widespread use of these assays in newborn screening and other diagnostic panels.

When I look back at my career over the last two decades, the thread that runs throughout is the desire to use my energy to alleviate suffering and to contribute something positive for humanity. Recently, Orchard announced new research programs in less-rare indications, including ALS and genetic subsets of frontotemporal dementia and Crohn’s disease. As we continue to investigate the potential of the HSC gene therapy approach, I am excited about the possibilities for patients and their families with this further expansion into areas of high unmet need. A side benefit of this pursuit has been the experience of working alongside other people who are oriented toward selflessness and a common purpose — and it has been the most rewarding part of my career so far.

On a larger scale, these moments of common purpose are the ones that remind us as an industry why we do what we do. The industry has come together in an unprecedented way this year to fight the COVID-19 pandemic, creating global collaboration unlike ever before. In this socially distanced time, it’s more important than ever to remind ourselves that we are part of a grander shared pursuit — shared with our colleagues, with industry partners, and with the patients and families we aim to serve. I’m hopeful that this reignited shared sense of purpose will continue and extend to other unmet needs in global health as we strive toward a world where the term ‘patient’ is only a temporary label.