In my career as a neurologist, I have encountered a wide range of rare, devastating neurodegenerative and neurometabolic diseases, many of which have no approved treatment options. Despite attempts to develop disease-modifying therapies for these diseases, complex pathogenic mechanisms coupled with difficulties for small molecules and biologics to cross the blood-brain barrier have hampered clinical development.

Five years ago, after over 20 years of working with neurodegenerative and neurometabolic diseases, I was drawn to Orchard Therapeutics, which at the time was a new biotech company founded on the goal of bringing one-time, potentially curative gene therapies to patients with these severe conditions. Even in the company’s early stages, I knew the gene therapy approach that Orchard employs was set to play a key role in addressing key pathogenic mechanisms of multiple inherited diseases. I was particularly excited by Orchard’s innovative approach of using a patients’ own (autologous) hematopoietic stem cells (HSCs) to cross the blood-brain barrier, distribute in the brain, engraft as microglial-like cells, and express the missing or faulty gene—a process which has the potential to persistently correct the underlying cause of disease in a single treatment.

Shortly after Orchard was established, I joined the team as head of clinical development for neurometabolic disorders and have recently become global head of translational medicine across our disease portfolio. Managing the development of the neurometabolic and neurological assets in our pipeline from translational research through clinical development and registration for the last five years has served as a strong foundation and natural transition into my new role working with cross-functional teams to maximize the probability of success of first in human studies for indications like frontotemporal dementia with progranulin mutations (GRN-FTD) and amyotrophic lateral sclerosis (ALS).

Today, Orchard has made significant progress across its neurodegenerative and neurometabolic portfolio, capped by the recent European Commission (EC) approval for its first HSC gene therapy for a neurometabolic disease, representing an extraordinary leap forward for the field and the promise of a new era in the treatment of severe genetic diseases. Bringing our first gene therapy to market in Europe is a remarkable achievement of our clinical development team, our partners at San Raffaele Telethon Institute for Gene Therapy and the rare disease community.

Our work doesn’t stop here, however, and we will continue working to harness the power of HSC gene therapy to bring potentially curative treatments to patients living with severe inherited conditions. We believe there is great potential for the application of HSC gene therapy in a growing range of neurometabolic and neurodegenerative disorders of high unmet need. Our understanding of the biology of disease, the mechanism by which HSC gene therapy exerts its effect and the clinical validation in rare diseases has helped pave the way for our development programs for less-rare neurometabolic and immunological conditions, including GRN-FTD, ALS and NOD2-Crohn’s disease.

I believe that Orchard’s HSC gene therapy approach has the potential to transform lives, and we are extremely excited about the possibilities for patients with the devastating genetic diseases we aim to treat.