BIO 462 Final Draft Sanfilippo Syndrome

Sanfilippo Syndrome

Mucopolysaccharidosis Type 3A (MPS3A)

Kate Jaggi

"Childhood Alzheimers"

Abby Grace Foundation

Summary

• Autosomal recessive
• Lysosomal storage disease
• SGSH gene (chromosome 17q25)
• Missing or defective N-heparin N sulfatase enzyme
• 1 in 70,000 births

Childhood Alzheimers"

Summary

• Autosomal recessive
• Lysosomal storage disease
• SGSH gene (chromosome 17q25)
• Missing or defective N-heparin N sulfatase enzyme
• 1 in 70,000 births

• Progressive dementia
• Hyperactive & aggressive behavior
• Degenerative physical systems
• Visceromegaly (large organs)

• Respiratory infections (leading cause of death)
• Life expectancy of 10-20 years

SYMPTOMS

Stages of Sanfilippo Syndrome

Stages of Sanfilippo Syndrome

ONSET OF CLINICAL FEATURES

• 2-6 years
• Early mental & motor delays
• Loss of language
• Difficult to diagnose
• Autism similarity

Stages of Sanfilippo Syndrome

ONSET OF CLINICAL FEATURES

NEUROLOGICAL DEGENERATION

• 2-6 years
• Early mental & motor delays
• Loss of language
• Difficult to diagnose
• Autism similarity

• 5-10 years
• Aggressive & hyperactive behavior
• Irregular sleep
• Seizures
• Chewing
• Significant dementia

Stages of Sanfilippo Syndrome

ONSET OF CLINICAL FEATURES

NEUROLOGICAL DEGENERATION

PALLIATIVE CARE & DEATH

• 2-6 years
• Early mental & motor delays
• Loss of language
• Difficult to diagnose
• Autism similarity

• 10-20 years
• Loss of motor skills (walking, talking, feeding)

• Growing stops
• Nonverbal
• Palliative care

• 5-10 years
• Aggressive & hyperactive behavior
• Irregular sleep
• Seizures
• Chewing
• Significant dementia

Children with Sanfilippo Syndrome

HAIDYN

LOGAN

OLIVIA

Haidyn, Logan, and Lev are children with Sanfilippo syndrome whose families advocate publicly to educate & raise funds for the treatment of MPS3A

Potential Future Therapies

Provide correct form of heparin N sulfatase

Potential Future Therapies

Get rid of heparin sulfate sugar

Introduce good copies of theSGSH gene

Potential Future Therapies

Correct misfolding in heparin N sulfatase

Potential Future Therapies

Regenerate & make correct heparin N sulfatase

Potential Future Therapies

Introduce good copies of the SGSH gene

Introduce good copies of the SGSH gene

Clinical Trials

• Early clinical trial results (Feb. 2023):
• Sustained engraftment of SGSH gene-corrected cells
• Higher levels of heparin N sulfatase enzyme activity
• Children (6-24 months) gaining skills

"These are encouraging results for children living with MPS-IIIA and their families, who currently have no effective treatment options."

Resources

• https://www.mdpi.com/1422-0067/21/21/7819
• https://kidshealth.org/en/parents/sanfilippo-syndrome.html#:~:text=Sanfilippo%20Syndrome%20Treated%3F-,There%20is%20no%20cure%20yet%20for%20Sanfilippo%20syndrome.,could%20be%20on%20the%20way.
• https://www.sanfilippo.org.au/blog/development-of-gene-therapies-for-sanfilippo#:~:text=Sanfilippo%20involves%20changes%20to%20one,being%20explored%2C%20including%20gene%20therapy.
• https://www.manchester.ac.uk/discover/news/early-results-of-gene-therapy-trial-for-childhood-dementia-show-promise/

Thank You