ADX-629 for Sjogren-Larsson Syndrome

Overseen By William B Rizzo, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: William Rizzo, MD

Must not be taking: Immunosuppressants, Corticosteroids, others

Disqualifiers: Malignancy, HIV, Cardiovascular, Renal, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

8 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests if ADX-629, a medicine taken by mouth, is safe and effective for people with Sjögren-Larsson syndrome (SLS). SLS is a rare genetic disorder that causes harmful fats to build up in the body. ADX-629 helps remove these harmful fats, which may reduce symptoms in the skin, brain, and eyes.

Will I have to stop taking my current medications?

The trial requires participants to stop using all topical creams 7 days before the study and any experimental drugs 1 month before the study. If you are on immunosuppressive therapy or certain systemic or topical medications, you must be willing to stop them 2 weeks before and during the study.

What makes the drug ADX-629 unique for treating Sjögren-Larsson syndrome?

The research does not provide specific information about how ADX-629 works for Sjögren-Larsson syndrome, so its unique aspects compared to other treatments are not clear from the available data. ^{1 2 3 4 5}

Who Is on the Research Team?

William B Rizzo, MD

Principal Investigator

University of Nebraska

Are You a Good Fit for This Trial?

Adults aged 18-50 with Sjogren-Larsson Syndrome (SLS), weighing at least 35 kg, able to swallow pills and follow the study plan. Participants must have ichthyosis, spasticity, a genetic confirmation of SLS, and agree to contraception if sexually active. Excluded are those in other studies, with certain health conditions or treatments that could affect results or safety.

Inclusion Criteria

Subject is able to swallow oral tablet medication and is willing to adhere to the study regimen.

Subject or subject's guardian is willing to provide written informed consent prior to the initiation of any study procedures. Assent will be solicited from subjects intellectually capable of providing assent.

Subject is willing to comply with all study procedures and availability for the duration of the study

Exclusion Criteria

Subject is currently participating in any other therapeutic clinical study.

Subject has a history of any other condition that, in the opinion of the Investigator, would compromise the subject's ability to comply with the protocol or that might compromise the subject's safety or the interpretation of the study results.

You had cancer within the last 5 years, except for certain types of skin or cervical cancer that have been treated with no sign of coming back.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral ADX-629 treatment for 12 weeks to assess safety and biochemical efficacy

12 weeks

Weekly contact for adverse events, monthly in-person visits for safety monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ADX-629

Trial Overview The trial is testing ADX-629's safety and effectiveness for treating SLS when taken orally for 12 weeks. It aims to reduce harmful fatty aldehydes believed to cause symptoms by trapping these molecules. The drug's impact on skin, neurological function, and eye health will also be explored.

How Is the Trial Designed?

Group I: ADX-629 treatment Experimental Treatment 1 Intervention

Open label treatment with ADX-629

Who Is Running the Clinical Trial?

William Rizzo, MD

Lead Sponsor

Trials

1

Recruited

8+

University of Nebraska

Lead Sponsor

Trials

563

Recruited

1,147,000+

Published Research Related to This Trial

Sjögren-Larsson syndrome (SLS) is a rare inherited disorder caused by mutations in the ALDH3A2 gene, leading to symptoms like ichthyosis, mental retardation, and spastic diplegia, as seen in two diagnosed brothers aged 12 and 20.

The study identified a novel homozygous mutation (c. 835 T > A) in the ALDH3A2 gene in these patients, contributing to the understanding of the genetic basis of SLS and its associated demyelinating disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Turkish family with Sjögren-Larsson syndrome caused by a novel ALDH3A2 mutation. Incecık, F., Herguner, OM., Rizzo, WB., et al.[2021]

The Sjögren-Larsson syndrome (SLS) gene has been successfully linked to a specific region on chromosome 17, based on a study involving families from the United States, Egypt, and Israel, which supports the idea of a single genetic cause for this rare disorder.

The identification of this gene location can aid in the diagnosis and carrier detection of SLS across diverse populations, as evidenced by the homozygosity observed in consanguineous families, indicating a shared genetic background.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic homogeneity in Sjögren-Larsson syndrome: linkage to chromosome 17p in families of different non-Swedish ethnic origins. Rogers, GR., Rizzo, WB., Zlotogorski, A., et al.[2020]

Sjögren-Larsson syndrome (SLS) is a rare genetic disorder that leads to intellectual disability, spastic diplegia or tetraplegia, and congenital ichthyosis, along with specific eye features like macular glistening dots.

This study presents two cases of SLS and highlights previously unreported changes in fundus autofluorescence, which could provide new insights into the ocular manifestations of the syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fundus autofluorescence changes in two cases of Sjögren-Larsson syndrome. Mirshahi, A., Piri, N.[2018]

In a study of four siblings with Sjögren-Larsson syndrome, three showed decreased activity of the fatty alcohol:NAD+ oxidoreductase complex, which is crucial for diagnosis, but none met the classic criteria for the syndrome, indicating variability in clinical presentation.

The findings suggest that the definition of Sjögren-Larsson syndrome should include the deficient enzyme activity as a key diagnostic criterion, even if the typical symptoms like ichthyosis, mental retardation, and spasticity are not fully present.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Redefining the Sjögren-Larsson syndrome: atypical findings in three siblings and implications regarding diagnosis. Nigro, JF., Rizzo, WB., Esterly, NB.[2019]

Sjögren-Larsson syndrome (SLS) is a rare genetic disorder caused by mutations in the ALDH3A2 gene, leading to a deficiency in an enzyme that helps break down fatty aldehydes, resulting in both skin and neurological symptoms.

The study highlights the variability of clinical manifestations of SLS among siblings, even in a case involving twins, suggesting that genetic factors and environmental influences may contribute to the differing severity and types of symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sjögren-Larsson syndrome: phenotypic variability in two brothers with a neurocutaneous disorder. Losito, L., Gennaro, L., De Rinaldis, M., et al.[2012]

Citations

1. India pubmed.ncbi.nlm.nih.gov

A Turkish family with Sjögren-Larsson syndrome caused by a novel ALDH3A2 mutation. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Genetic homogeneity in Sjögren-Larsson syndrome: linkage to chromosome 17p in families of different non-Swedish ethnic origins. [2020]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Fundus autofluorescence changes in two cases of Sjögren-Larsson syndrome. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Redefining the Sjögren-Larsson syndrome: atypical findings in three siblings and implications regarding diagnosis. [2019]

5. Italy pubmed.ncbi.nlm.nih.gov

Sjögren-Larsson syndrome: phenotypic variability in two brothers with a neurocutaneous disorder. [2012]