In late October 2020, Homology Medicines (“Homology“) announced its development of a new gene therapy program to treat patients with MPS II, or Hunter syndrome. Homology’s mission is to meet unmet needs for patients with rare genetic conditions. In this case, their therapeutic candidate, HMI-203, is delivered via human hematopoietic stem cell-derived adeno-associated virus vectors (AAVHSCs). Because of its ability to reach the root of the condition, HMI-203 could be a potentially more targeted and effective therapeutic option.
Developed by Homology, HMI-203 is an in vivo gene therapy. According to the American Society for Gene and Cell Therapy (ASGCT):
In vivo gene therapy means that therapy is administered directly the patient. The targeted cells remain in the body of the patient.
This is in contrast with ex vivo therapy, which is when cells are removed from the body and the cells are treated in vitro before being put back into the patient. In this case, HMI-203 is administered directly to the patient. Patients with Hunter syndrome often have IDS gene mutations. So HMI-203 works by providing the patient with functional genes. HMI-203 is administered intravenously.
Pre-clinical studies centered around this gene therapy were ultimately positive. They highlighted that one single dose of HMI-203 reduced glycosaminoglycans in various organs throughout the body. Since Hunter syndrome is characterized by glycosaminoglycans build-up to a toxic level, reducing glycosaminoglycans can reduce symptoms and improve patient outcomes.
Known as either mucopolysaccaridosis type II (MPS II) or Hunter syndrome, this debilitating disorder is inherited via X chromosome mutations. Because of this, most patients with Hunter syndrome are male; it is very rare for a female child to inherit this condition. The mutations occur in the IDS gene, preventing the breakdown of glycosaminoglycans, a type of sugar molecule. As this builds up, it results in intellectual and developmental delays. Symptom onset usually occurs around 2-4 years old. Symptoms and characteristics include:
- A broad nose with narrow nasal passages
- Difficulty breathing / respiratory distress
- Full lips and an enlarged tongue
- Macrocephaly, or an overly large head
- Hoarse voice
- Hydrocephalus, or fluid build-up within the brain
- Impaired vision
- Loss of coordination
- Enlarged spleen and liver
- Inguinal hernia, or when soft tissue protrudes through weak abdominal muscles
Learn more about Hunter syndrome.