Achromatopsia (ACHM)

Achromatopsia (ACHM), also known as rod monochromatism or total color blindness, is a genetically well-characterized disorder, with mutations in six identified genes causing varying degrees of cone dysfunction. As a research service provider, Protheragen is committed to the development of innovative therapies for achromatopsia and provides one-stop services to global pharmaceutical companies.

Overview of Achromatopsia (ACHM)

Achromatopsia (ACHM) is a type of genetic disease and is classified as a very rare, autosomal recessive retinal disorder. It severely affects the functioning of cone photoreceptors responsible for sensitive high-acuity daylight vision. This condition is accompanied by severe visual acuity loss, complete lack of color vision, photophobia, and nystagmus. This condition manifests itself either at birth or during the early years of childhood.

Fig.1 Known achromatopsia (ACHM) genes and their functions. (Michalakis S., et al., 2022)

The most common reason for this is changes or mutations in one of the six genes which are important in cone phototransduction. The most significant ones are known to be CNGA3 and CNGB3. These two mutations are the reason for up to 90% of cases. These genes encode subunits of the cone cyclic nucleotide-gated (CNG) channel, which is an essential part of the phototransduction cascade. These mutated genes lose their functionality and lead to the end accumulation of cyclic guanosine monophosphate (cGMP), resulting in further degeneration of cone photoreceptors.

Diagnostics Development for Achromatopsia

The most important method used to diagnose Achromatopsia is Genetic testing, as it can provide an accurate identification of necessary mutations. Next-generation sequencing (NGS) panels which target ACHM-causing genes like, CNGA3, CNGB3, ATF6, GNAT2, PDE6C, and PDE6H cater for a comprehensive detection of mutations. For instance, many pathogenic variants were reported in targeted sequencing of CNGA3 and CNGB3, allowing proper diagnosis and genetic counseling. In targeted testing that is inconclusive, whole-exome sequencing (WES) can be utilized for the identification of novel mutations or validation of presumed mutations.

Therapeutics Development for Achromatopsia

Achromatopsia can be treated most effectively through gene therapy which restores the function of affected cone photoreceptors through the transfer of genes. The availability of adeno-associated viral (AAV) vector systems has rapidly gained popularity because they are effective and have low immunogenicity. For instance, preclinical efficacy studies in animal models of CNGA3- and CNGB3-linked ACHM have shown marked restoration of cone function and activities involving vision after administration of wild-type genes via subretinal injection of AAV vectors.

Table 1. List of currently ongoing or recently completed achromatopsia
gene therapy clinical trials. (Michalakis S., et al., 2022)

Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.

Our Services

Protheragen is among the leaders in the research of Achromatopsia and provides end-to-end solutions for diagnosis and therapy development. We carry out genetic testing and preclinical studies which provide strong capabilities for the development of ACHM therapeutics.

Diagnostics Development

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

Therapeutic Development

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

Disease Models

• Cnga3 Knockout (KO) Mouse Model
• Cnga3 Sheep Model
• Cngb3 Knockout (KO) Mouse Model
• Cngb3 Knockout (KO) Dog Model
• Non-Human Primate Model of PDE6C-Linked ACHM

Protheragen is engaged in tailoring Achromatopsia diagnostics and therapeutic solutions by working closely with our clients. The agile design of our services permits the integration of brand-new technologies together with advanced research techniques, allowing our clients to remain competitive in Achromatopsia therapeutic development. If you are interested in our services, please feel free to contact us.

Reference

• Michalakis, Stylianos, et al. "Achromatopsia: genetics and gene therapy." Molecular diagnosis & therapy 26.1 (2022): 51-59.