SANDO Syndrome

SANDO syndrome are hereditarily heterogeneous mitochondrial diseases that frequently complicate Chronic Progressive External Ophthalmoplegia (CPEO) which is characterized by the gradual paralysis of the external eye muscles. Protheragen is a company with vast experience which offers comprehensive development services for diagnostics and therapeutics of SANDO Syndrome.

Overview of SANDO Syndrome

SANDO Syndrome or Sensory Ataxic Neuropathy, Dysarthria and Ophthalmoparesis is said to be an exceptionally intricate condition that is classified as rare. Even so, it has a great impact on the muscular and nervous systems. Cases suffering from SANDO syndrome show symptoms of ophthalmoplegia, ataxia, and dysarthria which all portray sensory dysfunction. Most cases show symptoms of this disorder in adulthood and it, unfortunately, gets worse with time. Mutations to the POLG gene causes dysfunctional expression of the DNA polymerase gamma enzyme which serves as the primary rationale behind this syndrome. This enzyme, regarded as the guardian of mitochondrial DNA, becomes dysfunctional and leads to deletions of the mitochondrial DNA which in turn causes impairment in high energy performing muscles and neuronal tissues.

Fig.1 Diagnostic genetic algorithms including SANDO syndrome. (Kierdaszuk B., et al., 2020)

Diagnostics Development for SANDO Syndrome

• Genetic Testing and Sequencing
  Identifying the mutations in the POLG gene is the primary objective of molecular diagnostics pertaining to SANDO Syndrome. Next generation sequencing NGS has enabled the detection of these mutations with great detail. Pathogenic variants in POLG are usually detected by whole exome sequencing WES or by targeted gene panels.
• Functional Assays
  Beyond sequencing the DNA, functional assays are required to assess the consequences of POLG mutations on mitochondrial physiology. qPCR and Southern blotting are techniques used to determine the mitochondrial genome copy number and deletion rate. These methods reveal the scope of mitochondrial dysfunction and assist in the genetic findings.
• Biomarker Identification
  The latest trends in the molecular diagnostics is that of searching for biomarkers which can contribute towards early detection of a problem and subsequent monitoring of its progression. For example, metabolomic profiling has shown specific metabolic signatures that might indicate mitochondrial dysfunction relevant to SANDO Syndrome.

Therapeutics Development for SANDO Syndrome

Our Services

Protheragen offers comprehensive services for the development of diagnostics and therapeutics for SANDO Syndrome. Our expertise in molecular diagnostics includes advanced genetic testing and functional assays to identify and characterize POLG mutations. In the realm of therapeutics, Protheragen leverages cutting-edge research to develop innovative therapeutics for SANDO Syndrome. Our services encompass the design and implementation of preclinical studies, gene therapy development, and the evaluation of therapeutics.

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

• POLG Mutant Mouse Models
• Ethidium Bromide-Induced Mitochondrial DNA Depletion Models
• POLG Knockdown Zebrafish Models
• POLG Mutant Canine Models

Protheragen specializes in creating relevant in vitro and in vivo models of SANDO Syndrome. Cell lines harboring POLG mutations and animal models recapitulating the disease phenotype are used to study pathogenic mechanisms and test therapeutic candidates. These models provide valuable insights into disease progression and therapeutic efficacy. If you are interested in our services, please feel free to contact us.

References

• Kierdaszuk, Biruta, et al. "Progressive External Ophthalmoplegia in Polish Patients—From Clinical Evaluation to Genetic Confirmation." Genes 12.1 (2020): 54.
• Bandettini di Poggio, Monica, et al. "Dopamine-agonist responsive Parkinsonism in a patient with the SANDO syndrome caused by POLG mutation." BMC medical genetics 14 (2013): 1-4.
• Lovan, Alyson, Ihtsham ul Haq, and Nikhil Balakrishnan. "Diagnostic challenges in movement disorders: Sensory Ataxia Neuropathy Dysarthria and Ophthalmoplegia (SANDO) syndrome." Case Reports 2013 (2013): bcr2013010343.