Both the 3rd Annual Gene Therapy for Neurological Disorders meeting and the ADVANCE 2022 Sanfilippo Community Conference were held in July 2022. During both meetings, researchers presented new data from the Phase 2/3 AAVance study. The study was evaluating safety, efficacy, and tolerability of LYS-SAF302 for patients aged 6 months+ with Sanfilippo syndrome type A. According to Sanfilippo News, the trial data – which followed patients for two years following treatment – highlighted the benefits of LYS-SAF302. 

What is LYS-SAF302?

Developed by Lysogene, LYS-SAF302 is an investigational gene therapy which:

delivers a functional copy of the human SGSH gene directly to brain cells using the adeno-associated virus carrier, AAVrh.10, which has a particular tropism for cells in the CNS. By providing a functional version of SGSH, the treatment may provide a permanent source of functional enzyme in the brain [and] in turn may help stabilize, or even reverse, the damage to patients’ brain cells.

LYS-SAF302 is administered one time through intracerebral infusion.

Within the AAVance study, researchers sought to understand the potential efficacy of LYS-SAF302. Prior studies had shown that LYS-SAF302 reduced heparan sulfate levels in patients after 6-12 months. 

The new data centered around the impact of LYS-SAF302 after two years of treatment. Findings included:

• The treatment helped reduce heparan sulfate levels in cerebrospinal fluid (CSF) by an average of around 20%. 
• Patients aged 10 months, 13 months (1 year, 1 month), and 31 months (2 years, 7 months) saw improved cognitive, language, and motor function. The treatment also stabilized disease progression, cognitive development, and language and motor skills in other patients aged 24 months (2 years), 30 months (2 years, 6 months), and 31 months (2 years, 7 months). 

In the future, Lysogene hopes to pursue drug approval.

About Sanfilippo Syndrome (MPS III)

Sanfilippo syndrome, or mucopolysaccharidosis III (MPS III), is a rare and inherited lysosomal storage disoder. There are four subtypes: A, B, C, and D. In each subtype, genetic mutations cause enzyme deficiencies which prevent the body from breaking down long chains of sugar molecules called mucopolysaccharides. Type A is characterized by an abnormal heparan N-sulfatase enzyme, which causes heparan sulfate to accumulate in bodily tissues. This can not only cause tissue damage, but severe damage throughout the body. Sanfilippo syndrome type A is considered to be the most severe form. Symptoms often appear in early childhood, sometimes before a child turns 1. Significant learning ability declines may occur in the coming years. Other symptoms can, but do not always, include:

• Chronic Diarrhea
• Delayed speech
• Intellectual and developmental delays
  • Note: Some children may also show signs of developmental regression.
• Sleep disturbances
• Macroglossia (an enlarged tongue) 
• Macrocephaly (an abnormally large head)
• Visual impairment
• Enlarged spleen and liver
• Frequent or recurrent respiratory infections
• Hearing loss
• Umbilical or inguinal hernia
• Behavioral problems
• Arthritis
• Seizures