Lysosomal Storage Disorders

We are working to bring a potential first- and best-in-class gene therapy to patients with Gaucher disease Type 1.

Freeline aims to change the lives of people with Lysosomal Storage Disorders (LSDs), a group of inherited metabolic diseases with high unmet medical needs. LSDs are caused by a dysfunction or deficiency of particular enzymes to metabolise various substrates contained in lysosomes, resulting in substrate accumulation. Substrate accumulation damages cells in different organs, depending on which enzyme the patient is deficient in. There are nearly 50 different Lysosomal Storage Disorders described today, find out more.

Some Lysosomal Storage Disorders can be treated with enzyme replacement therapy, substrate reduction therapy, and chaperone therapy. But these treatments are a burden for patients and do not offer full symptom relief. Treatments need to be taken throughout the life-span and may not stop the progression of disease or remove pre-existing substrate build-up that causes organ damage. Gene therapy has the potential to provide high levels of the missing enzyme and continuous expression without peaks and troughs. Gene therapy could offer real hope for better lives for people with Lysosomal Storage Disorders.

Diagnosis

Lysosomal Storage Disorders are diagnosed with a biochemical enzymatic assay or through genetic testing at a specialised facility. Many Lysosomal Storage Disorders remain undiagnosed, although new genetic screening programs have shown that as many as 1 in 5-8,000 new-born babies may suffer from a Lysosomal Storage Disorder (Fuller M, 2006). 

Symptoms and classification

Lysosomal Storage Disorders are classified according to the missing enzyme caused by the genetic mutation. Symptoms vary, depending on the particular enzymatic disorder and other variables such as the age of onset. They can range from mild to severe and may include, for example, kidney failure, pulmonary and cardiac problems, issues with abnormal bone growth, intestinal symptoms and pain, developmental delay, movement disorders, seizures, dementia, deafness, and blindness.

Current treatments

No cures exist for Lysosomal Storage Disorders, and treatment is mostly to alleviate symptoms – although bone marrow transplantation, enzyme replacement therapy, substrate reduction therapy and chaperone therapy have been tried with some success. Early diagnosis and treatment may prolong life and reduce disability for some Lysosomal Storage Disorders.

If demonstrated to be safe and effective, gene therapy provides an opportunity for a potentially life-changing therapy for people with Lysosomal Storage Disorders. It can offer not only high and sustained levels of the missing enzyme, but also potentially a life-long treatment requiring only a single infusion.