Farber disease is a lysosomal storage disorder that is characterized by deficiency of the acid ceramidase enzyme, first described by Dr. Sidney Farber in 1947. Acid ceramidase primarily acts in the lysosome to modulate levels of ceramide, a bioactive lipid that is a major component of cell membranes but that can have proinflammatory and proapoptotic properties when in excess concentration. Abnormal accumulation of ceramide leads to macrophage driven inflammation and multiple organ system pathology, including potential impacts on the bone, cartilage, immune system, central nervous system (CNS), lungs, and other internal organs. It leads invariably to progressive disease, with profound morbidity and often premature death.
The cardinal symptoms of Farber disease are subcutaneous inflammatory nodules, joint disease (arthritis and/or contractures), and a hoarse or weak voice. These symptoms may vary in severity from patient to patient and it may take years for all the symptoms to appear together. These last two factors can lead to long delays in the diagnosis of Farber disease, or a misdiagnosis of juvenile idiopathic arthritis (JIA).
In 1995, the first substantial purification of human acid ceramidase was accomplished by Dr. Edward H. Schuchman’s team at the Icahn School of Medicine at Mount Sinai in New York City. The purified enzyme was found to be an ~50 kDa polypeptide comprised of α and β-subunits. The availability of the highly purified enzyme led to the isolation of the cDNA and gene encoding AC (ASAH1), the identification of the first mutations causing Farber disease, and the production of recombinant human acid ceramidase (rhAC). Dr. Schuchman went on to demonstrate that skin fibroblasts from patients with Farber disease showed significant reduction of ceramide when exposed to rhAC. Importantly, in a mouse model of Farber disease exhibiting a very severe phenotype that results in early death, injected rhAC was able to reduce levels of ceramide and inflammation in the blood and in the affected tissues and organs, with an excellent safety profile. Dr. Schuchman serves on Aceragen’s Scientific Advisory Board.
Based on these exciting developments, Aceragen is engaged in the clinical development of ACG-801 (rhAC). A first-ever prospective and retrospective natural history study of patients with Farber disease has been completed, our additional plans include evaluating efficacy and safety in a potentially single study for registration and scaling manufacturing in preparation for commercialization. In parallel, Aceragen is committed to engaging and working to support the community of patients and families impacted by Farber disease. We trust that our work will eventually benefit every patient with Farber disease, and acid ceramidase deficiency, no matter where they are in the world.
Patients and their families are our focus and the most important stakeholders in our work to develop therapies as efficiently as possible. The data collected to date has led to a better understanding of the disease, symptoms, and prognosis; faster recognition and diagnosis of patients; and moving the development of a potential enzyme replacement therapy forward more quickly and efficiently. Additionally, Aceragen has partnered with genetic testing companies to offer no-cost diagnostic testing to shorten the path to diagnosis for patients with Farber disease worldwide.
If you or a loved one have been diagnosed or suspect you have Farber disease and want to find out more about the disease, availability of diagnostic testing or the clinical development program please contact us via firstname.lastname@example.org and we will be sure to connect with you as soon as possible.
- Single registrational study alignment with FDA/EMA for Farber disease
- Potential approval in USA and EU within approximately 2024 – 2025 (Orphan & Fast-Track designations granted)
- Opportunity for expansion into additional mechanistically aligned rare indications