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Project Description

Please note that we are a research service provider, not a pharmacy or clinic, so we are unable to see patients and do not offer diagnostic and treatment services for individuals.

Choroideremia

Affecting roughly 1 in 50,000 to 100,000 people, Choroideremia (CHM) is an X-linked chorioretinal dystrophy. At Protheragen, we offer a comprehensive suite of choroideremia diagnostics and therapeutics development services. Our services are designed to support the entire pipeline of choroideremia research, from initial genetic screening to preclinical therapeutic testing.

Overview of Choroideremia

Choroideremia is an unusual type of eye disease caused by progressive degeneration of the retinal pigment epithelium (RPE), photoreceptors, and choriocapillaris, which leads to growing vision loss. It occurs due to the CHM gene which causes mutations. This gene is responsible for directing another gene (REP1) which is critical for premising certain proteins called Rab GTPases that manage transport vesicles within the cell. Usually, cases report having difficulty seeing at night (nyctalopia) during early childhood. This is often followed by loss of peripheral vision and eventually leads to loss of central vision or sight by midlife.

A case analysis of retinal images and microperimetry images in advanced choroideremia.

Fig. 1 Retinal images and microperimetry plot from a case with advanced choroideremia. (MacLaren R. E., et al., 2023)

Diagnostics Development for Choroideremia

Genetic Testing

The advent of next-generation sequencing (NGS) technologies has broadened the horizons of genetic testing by enabling thorough scans of the CHM gene to detect particular mutations. These mutations may include deletions, insertions, nonsense mutations, and missense mutations which may all have profound and differing repercussions on the severity of the disease and its progression.

Molecular and Cellular Assays

A cellular and molecular approach is imperative for studying the function of CHM mutations. Assays measuring Rab prenylation in cells from patients can yield important information about the degree of intracellular trafficking impairment. Furthermore, cell culture models with patient-derived fibroblasts or induced pluripotent stem cells (iPSCs) enable investigation of REP1 deficiency and evaluation of potential therapeutic strategies.

Therapeutics Development for Choroideremia

Gene Therapy: This strategy seeks to rectify the problematic CHM gene by substituting it with a healthy one through viral vectors, most commonly adeno-associated viruses (AAVs). The vector is delivered either subretinally or intravitreally to the affected retinal cells.
Nonsense Suppression Therapy: Such an approach applies to individuals with nonsense mutation in the CHM gene. Medications are administered to facilitate the translational readthrough of early cease codons, resulting in a fully functional REP1 protein being synthesized.
Antisense Oligonucleotides (ASOs): ASOs are abbreviated as Antisense Oligonucleotides, which are short synthetic DNA or RNA molecules. Antisense Oligonucleotides can be tailored to CHM pre-mRNA and are designed to address particular CHM splicing flaws to optimize the functionality of REP1 synthesis in Choroideremia.

Table 1. Summary of choroideremia gene therapy. (Abdalla Elsayed M. E., et al., 2023)

Drug Design	Location	Vector	Phase	Clinicaltrials.gov Identifier and Study Start Date
AAV2-hCHM	University of Philadelphia, USA	Subretinal	I/II	2341807 (January 2015)
r.AAV-REP1	University of Oxford, UK	Subretinal	I/II	1461213 (October 2011)
r.AAV-REP1	University of Alberta, Edmonton, Alberta, Canada	Subretinal	I/II	2077361 (April 2015)
r.AAV-REP1	Tuebingen, Germany	Subretinal	II	2671539 (January 2016)
r.AAV-REP1	University of Miami, Miami, USA	Subretinal	II	2553135 (September 2015)
r.AAV-REP1	University College London & University of Oxford, UK	Subretinal	II	2407678 (August 2016)
r.AAV-REP1	Gemini, Biogen	Subretinal	II	3507686 (November 2017)
Low-dose and high-dose r.AAV-REP1	STAR, Biogen	Subretinal	III	3496012 (December 2017)

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 provides complete services that aid in the development of diagnostics and therapeutics for Choroideremia. These services encompass the entire process of developing therapeutics, starting from target identification, validation, and preclinical studies.

Diagnostics Development

Therapeutic Development

Preclinical Research

Disease Models

Fibroblast and Lymphoblast Models
Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium (iPSC-RPE) Models
CHM Mutant Mouse Models
CHM Mutant Zebrafish Models

Protheragen recognizes the importance of customized approaches in choroideremia research. We offer tailored services to meet the specific needs of our clients, ensuring that each project is optimized for success. If you are interested in our services, please feel free to contact us.

References

MacLaren, Robert E., et al. "Subretinal timrepigene emparvovec in adult men with choroideremia: a randomized phase 3 trial." Nature medicine 29.10 (2023): 2464-2472.
Sarkar, Hajrah, and Mariya Moosajee. "Choroideremia: molecular mechanisms and therapies." Trends in Molecular Medicine 28.5 (2022): 378-387.
Abdalla Elsayed, Maram EA, et al. "Choroideremia: the endpoint endgame." International Journal of Molecular Sciences 24.18 (2023): 14354.