Senior-Locken Syndrome (SLSN)

Senior-Loken Syndrome (SLSN) is classified as a rare autosomal recessive genetic problem that is characterized by the presence of NPHP and retinal degeneration which typically presents as Leber congenital amaurosis (LCA) or retinitis pigmentosa. Protheragen's services encompass the full spectrum of SLSN research and development, from genetic analysis and diagnostic tool development to preclinical testing of novel therapies.

Overview of Senior-Locken Syndrome (SLSN)

Senior-Loken Syndrome (SLSN) is marked by nephronophthisis which is an autosomal recessive cystic kidney disease alongside retinal degeneration. While nephronophthisis is the second most common hereditary reason for end-stage kidney disease during childhood and adolescence, retinal degeneration is a progressive disease that causes vision loss and sometimes total blindness.

Fig.1 A novel mouse model for SLSN. (Vogel, P., et al., 2015)

The pathophysiology of this syndrome is associated with changes in the primary cilia of the cells and it results from the inability of the cilia to perform normal cellular signaling functions such as maintaining homeostasis. Abnormalities of cilia caused by mutations in the NPHP1, CEP164, CEP290, INVS, IQCB1, SDCCAG8, TRAF3IP1, and WDR19 genes often result in non-functional or malformed cilia which leads to impaired renal tubules and photoreceptor cells. These changes cause cystic kidney disease and retinal degeneration

Diagnostics Development for Senior-Locken Syndrome

Genetic Testing

Genetic testing has assumed a pivotal role in soliciting diagnosis of SLSN. Gene panels are widely utilized for next generation sequencing (NGS) where known causative genes are targeted. These panels identify substitution of nucleotides, small-scale deletions/insertions, and mutations in splice sites. When NGS results are ambiguous, more sensitive methods such as Sanger sequencing and MLPA (Multiplex Ligation-Dependent Probe Amplification) for large deletions or duplications are applied. Once pathogenic changes are detected in these genes, the diagnosis is definitively made and further family investigations and risk evaluations are possible.

Therapeutics Development for Senior-Locken Syndrome

Gene therapy has the potential to target SLSN's underlying genetic structure. Techniques like CRISPR-Cas9 mediated gene editing may be utilized to rectify the alterations in causative genes such as NPHP1, and CEP164. Moreover, small molecules that can target components of ciliary signaling pathways or those that stabilize cilia could prove beneficial. For instance, there is proof that restoring expression of the ciliary protein INPP5E, which is not expressed in NPHP1 deficient cells, can restore ciliary function and thus ameliorate the NPHP1 disease.

Our Services

Protheragen offers comprehensive services for the development of diagnostics and therapeutics for Senior-Loken Syndrome. We also offer sophisticated preclinical research services by creating and testing novel therapeutic targets using modern technologies.

Diagnostics Development

• Karyotype Analysis Service
• Omics Analysis Service
• Biomarker Development Service
• Artificial Intelligence Service

Therapeutic Development

• Small Molecule Drug
• Cell Therapy
• Gene Therapy
• Therapeutic Antibody
• Therapeutic Peptide
• Therapeutic Protein

Preclinical Research

• Pharmacodynamics Study Services
• Pharmacokinetics Study Services
• Drug Safety Evaluation Services

Disease Models

• Tmem218^-/- Mouse Model
• Nphp1^-/- Mouse Model
• Nphp3^-/- Mouse Model
• Nphp4^-/- Mouse Model
• Nphp6^-/- Mouse Model
• Nphp11^-/- Mouse Model

From advanced genomic analyses to the establishment of relevant disease models, Protheragen is committed to driving the field of SLSN therapeutics development. If you are interested in our services, please feel free to contact us.

References

• Vogel, P., et al. "Nephronophthisis and Retinal Degeneration in Tmem218–/–Mice: A Novel Mouse Model for Senior-Løken Syndrome?." Veterinary pathology 52.3 (2015): 580-595.
• Abeshi, Andi, et al. "Genetic testing for Senior-Loken syndrome." The EuroBiotech Journal 1.s1 (2017): 99-101.
• Ning, Ke, et al. "Defective INPP5E distribution in NPHP1-related Senior–Loken syndrome." Molecular Genetics & Genomic Medicine 9.1 (2021): e1566.