Help us create gene therapy for children with Smith-Lemli-Opitz-Syndrome

Gene Therapy for Children with Smith–Lemli–Opitz Syndrome (SLOS)

Smith–Lemli–Opitz syndrome (SLOS) is a rare, severe genetic disorder caused by a mutation in the DHCR7 gene, which is responsible for the production of cholesterol—essential for proper brain and body development.

What is SLOS?

The disease is caused by a mutation in the DHCR7 gene. This gene encodes an enzyme required in the final step of cholesterol production. As a result of its dysfunction:

• the body cannot properly synthesize cholesterol,
• cholesterol deficiency occurs,
• at the same time, 7-dehydrocholesterol and 8-dehydrocholesterol accumulate, which may have toxic effects.

Key characteristics of SLOS:

• moderate to severe intellectual disability, developmental delay, microcephaly, hypotonia (reduced muscle tone), and behavioral problems, including autism spectrum features;
• growth disorders and failure to thrive;
• characteristic facial features, cleft palate, postaxial polydactyly (extra fingers or toes), and typical 2–3 toe syndactyly (fusion of the second and third toes);
• other: urogenital abnormalities, congenital heart defects, lung hypoplasia, gastrointestinal problems (e.g., feeding difficulties, Hirschsprung disease), cataracts, and photosensitivity.

Currently available treatment

At present, there is no effective causal treatment—only symptomatic therapy including:

• cholesterol supplementation,
• symptomatic treatment (e.g., surgeries for heart defects),
• developmental, neurological, and dietary therapies.

Why is cholesterol supplementation not enough?

Cholesterol supplementation has limited effects because the problem in SLOS is more complex than a simple deficiency.

• The defective DHCR7 enzyme does not properly convert 7- and 8-dehydrocholesterol into cholesterol. As a result, these compounds accumulate in the body, and their oxidized forms (oxysterols) may be toxic, especially to the brain. Cholesterol supplementation does not remove these substances.
• Supplemented cholesterol does not effectively cross the blood–brain barrier in amounts sufficient to correct brain deficiency . The brain must produce its own cholesterol, and in SLOS this process is impaired. Therefore, even if blood cholesterol levels improve, the brain may still remain deficient.

Is SLOS a good candidate for gene therapy?

• SLOS is a single-gene disorder (DHCR7 mutation), making it a strong candidate for gene therapy—introducing a correct copy of the gene could theoretically be sufficient.
• The disease mechanism is well understood: cholesterol deficiency and accumulation of toxic precursors.
• Restoring DHCR7 enzyme activity could directly correct the metabolic defect—a classic target for gene therapy.
• The DHCR7 enzyme functions in multiple tissues, so even partial restoration may have systemic benefits.
• Current treatment options are limited in effectiveness.

How could gene therapy impact the lives of SLOS patients?

Since gene therapy for SLOS is currently in early research stages, its actual effects are not yet known and cannot be guaranteed. Potential benefits would depend on factors such as mutation type, disease severity, and timing of treatment—the earlier, the better.

However, there is scientifically grounded hope that effective gene therapy could improve patients’ quality of life.

Key potential benefits:

• Treating the root cause

Current approaches focus only on symptom management. Gene therapy could deliver a correct copy of the DHCR7 gene, enabling cells to produce a functional enzyme. This could improve cholesterol synthesis and reduce the accumulation of toxic precursors.

• Improved brain function and neurological development

Cholesterol plays a key role in brain development, especially in early childhood. Gene therapy may support cognitive function, speech and communication development, and help reduce behavioral challenges, potentially lessening the degree of intellectual disability. However, some changes in the brain may not be reversible.

• Reduced toxicity in the body

Restoring DHCR7 activity could lower levels of 7- and 8-dehydrocholesterol and their toxic derivatives, benefiting not only the brain but other organs as well.

• Better physical development and overall health

Improved cholesterol metabolism may support growth and weight gain, enhance muscle tone, improve the function of internal systems, and reduce the risk of health complications.

How can we help?

In 2025, the Purestone Foundation partnered with Gene2Cure to launch a gene therapy project for children with SLOS. The project is led by a research team headed by Prof. Leszek Lisowski from the Children’s Medical Research Institute (CMRI) in Sydney.

The team is developing a custom-designed gene therapy based on AAV vectors, aimed at delivering a correct copy of the DHCR7 gene and restoring its function.

What do we need?

Although we have the knowledge, experience, and a dedicated scientific team, financial support is essential to bring this project to completion—from preclinical studies, through clinical-grade production, to the first administration in patients. Every contribution brings us closer to this goal.

This project could be a global breakthrough—not only for children with SLOS, but also as a model for developing gene therapies for other rare genetic diseases.

Cost of therapy development

The estimated cost of developing the therapy is around €5 million. This includes research and manufacturing for experimental administration to a group of approximately 10–15 patients

This translates to about €500 000 per patient, which—despite the high total cost—creates an opportunity for shared funding.

Due to the rarity of the disease, such projects are not a priority for large pharmaceutical companies, which focus on solutions with greater market potential. This means that funding must come from patients’ families and non-profit organizations.

At the same time, this has an important advantage: it may allow for more accessible pricing compared to traditional commercial development models .

Join us—together we can achieve this goal

If you are a parent, doctor, scientist, donor, or simply someone who believes in medical progress—you can be part of this change.

By supporting this project, you are not only helping one child—you are helping build the foundation for therapies of the future.

Download a description of gene therapy

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