In October 2020, Arrowhead Pharmaceuticals (“Arrowhead”) announced a new collaboration and licensing agreement with global biopharmaceutical company Takeda Pharmaceutical Company Limited (“Takeda”). Together, the pair will develop and commercialize an investigational RNA interference (RNAi) treatment for patients with liver disease associated with alpha-1 antitrypsin deficiency (A1AD).
RNAi
According to an article published in Biotechnology Advances, RNAi therapies:
such as siRNA or microRNA (miRNA) are a new class of drug molecules that can be used to treat disease by attacking messenger RNA.
LABiotech.eu continues by explaining:
RNAi is a biological process in which small RNA molecules inhibit gene expression by neutralizing targeted mRNA molecules. These [siRNA or miRNA] molecules can be engineered to ‘hack’ the RNAi machinery and are promising for silencing specific genes which are responsible for diseases such as hemophilia, cancer, or even age-related vision loss.
In this case, ARO-AAT is a first-in-class treatment which tackles mutant alpha-1 antitrypsin (Z-AAT) protein. Z-AAT plays a role in disease progression for patients with A1AD-related liver disease. By preventing this proinflammatory protein from being expressed and produced, ARO-AAT could potentially prompt liver regeneration and healing.
Alpha-1 Antitrypsin Deficiency (A1AD)
Caused by SERPINA 1 gene mutations, alpha-1 antitrypsin deficiency (A1AD) is an inherited condition characterized by low alpha-1 antitrypsin (A1AT) levels. Normally, SERPINA 1 helps produce A1AT, which provides protection from a proinflammatory neutrophil (white blood cell) called elastase. Elastase usually fights infection. But when someone lacks A1AT, elastase begins to attack body tissues like the lungs or liver. Generally, A1AD causes liver damage when it becomes trapped and accumulates. A1AD affects people of European ancestry more than Asian or Black communities.
Symptoms of A1AD vary based on what part of the body is affected. However, they include:
- Wheezing
- Difficulty breathing or shortness of breath
- Fatigue
- Jaundice
- Exercise intolerance
- Dark urine
- Liver cirrhosis
- Unintended weight loss
- Skin lesions or painful lumps under the skin
- Frequent respiratory infections
- Emphysema
- High heart rate when standing
- Abdominal distension
- High liver enzyme levels
- Swollen hands and feet
- Extreme itching
An estimated 10% of all pediatric patients and 15% of adult patients with A1AD go on to develop liver disease. Learn more about A1AD here.
