Lysosomal Disorders: Bridging the way to the future of genetic treatments

Lysosomal storage disorders represent a small portion of diseases of inner cell metabolism but are a big influence on new treatment options for genetic disorders. The lysosome is a small bag of enzymes inside each cell that recycles large, complex molecules that help create the specific structures of body (brain, bones, heart, blood vessels, liver, eyes, and more) by breaking them down into their smaller parts to reuse and keep things running smoothly. When one of the enzymes is broken through a mutation, these large, bulky molecules start building up, leading to immense distortion and cells that cannot do their jobs. Depending on where in the body this happens and how poorly the enzyme works, the symptoms are different and are progressive, leading to over 60 types of lysosomal disorders!

Thankfully, there are a group of dedicated patients, families, doctors, and researchers who have devoted their time and energy to reverse the problems caused by the build-up of these particles.  More than 25 years ago the first brave pioneers in this group, patients with Gaucher disease led the way forward with enzyme replacement therapy, a way to give back the enzyme that is broken. Though this remedy is an imperfect replacement, it radically changed the health of people affected and ushered a new strategy for treatment. We are proud that Pittsburgh was a site for these revolutionary discoveries through the work of John Barranger, MD. This initial approach has been expanded to include several more disorders over the years and has exploded in recent years to include new approaches such as:  giving the enzyme in new delivery packages, directing the enzyme to new tissues, correcting the gene itself, and learning more about how these disorders influence normal, healthy tissue and cell function.

All this effort culminates in a yearly meeting that brings together a variety of providers (doctors, nurses, researchers, patients, and companies) with the hope and expectation of improving the quality of life for our patients and families through collaboration (LysosomalWORLD). A variety of disorders are discussed, analyzed and illuminated through this conference. The emphasis changes from year to year (Chart 1, topics discussed in the main meeting hall) and the interests of individual groups, providers and patients (Chart 2, poster session topics). The scope of these diseases from tiny interactions within the cell to worldwide economic impacts are brought to light, new partnerships are brokered, old connections are strengthened and then we bring this knowledge back to our individual clinics and patients.



I am so amazed that I get to work with this group of patients who represent a kaleidoscope of backgrounds, diagnostic and treatment types. I get to work with a fantastic team (see below) who have decades of experience bringing clinical care and research together for the benefit of our local patients and hope to impact the greater lysosomal community, as well. We are working hard to return Pittsburgh to the forefront of care and are enthusiastic about being an active part of this new second wave of gene therapy and other treatments of Lysosomal storage disorders. We hope to honor the legacy of Dr. Barranger as we move forward together!

Meet the Lysosomal team at UPMC Children’s Hospital:

• Damara Ortiz, MD
• Nadene Henderson, MS, LCGC
• Kayla Segady, RN
• Joshua Barch, MS, LCGC
• Areeg El-Gharbawy, MD
• Uta Lichter-Konecki, MD, PhD
• David Finegold, MD