Lysosomal Storage Disorders


Lysosomal Storage Diseases are Ideal Candidates for Lentiviral-Based Gene Therapy

Lysosomal storage disorders are ideal candidates for the potential curative benefit derived through AVROBIO’s lentiviral-based technology. Lysosomal storage disorders are caused by a single-gene defect that leads to an enzyme deficiency. Due to the catalytic nature of the enzyme, studies have demonstrated that only 1-5% of normal intracellular enzyme activity is required to correct the underlying metabolic defect.1

Understanding Lysosomal Storage Disorders

Lysosomal storage disorders (LSDs) comprise a group of > 50 distinct genetic disorders with one common characteristic; each disease results from a deficiency of a specific lysosomal enzyme or protein function that causes the storage of a substrate within the lysosome.2

Lysosomes are organelles within the cell that function as the digestive system or recycling center of the cell serving to degrade intracellular materials.3 When there is a genetic defect in a specific gene that encodes for one of the 50+ lysosomal enzymes, also known as acid hydrolases, materials contained within the lysosome are unable to be degraded or recycled, which results in the accumulation and storage of a substrate within the lysosome. The accumulated substrate causes cellular dysfunction, giving rise to the signs and symptoms of the specific disease.

The Clinical Presentation of Lysosomal Storage Disorders

Lysosomal storage disorders are generally classified by the accumulated substrate and despite this attempt at classification, many clinical similarities are present cross the 50+ identified lysosomal storage disorders. Most lysosomal storage disorders have a wide continuum of clinical presentation including a varied age of onset, severity of symptoms and whether there is evidence of central nervous system (CNS) involvement. The wide array of symptoms can be seen even within a single disorder.

The severity of the disease can also depend on the cells, tissues and organs in which the substrate accumulates. Many of the lysosomal storage disorders impact the heart, kidney, spleen and/or liver, the skeleton and approximately half of the disorders affect the CNS.4 Most individuals living with a lysosomal storage disorder are born outwardly healthy with disease symptoms developing progressively over time.

How Common are Lysosomal Storage Disorders?

With the advent of newborn screening panels testing for several lysosomal storage disorders (LSDs), screening studies aimed at detecting patients at an earlier age and an increasing number of patients with milder forms of the disorders being diagnosed, the current figures may underestimate the true incidence of lysosomal storage disorders.

AVROBIO’s Clinical Trials

AVROBIO is currently enrolling a Phase 2 study of our investigational lentiviral gene therapy for Fabry disease. The clinical trial is being conducted in Canada and Australia. More information is here. AVROBIO’s academic collaborators at the University of California, San Diego are enrolling a Phase 1/2 trial of an investigational gene therapy for cystinosis. More information is here.

Desnick RJ, Schuchman EH. Enzyme Replacement Therapy for Lysosomal Storage Diseases: Lessons from 20 Years of Experience and Remaining Challenges.
Annu Rev. Genomics Hum. Genet. 2012; 13:307-35

2 Fuller M et al. Epidemiology of lysosomal storage diseases: an overview. In: Mehta A, Beck M, Sunder-Plassmann G, editors. Fabry Disease: Perspectives from 5 Years of FOS. Oxford: Oxford PharmaGenesis; 2006. Chapter 2. Available from:

Cooper GM. The Cell: A Molecular Approach.
2nd edition. Sunderland (MA): Sinauer Associates; 2000. Lysosomes. Available from:

4 Meikle PJ et al. Prevalence of lysosomal storage disorders.
JAMA. 1999;281(3):249–54