Overview of Research

Overview of Research

Advancing Research

At CureARS, collaboration and partnership is key. We believe in the power of partnerships between families, researchers, and clinicians to accelerate research and find a cure. Your participation in research studies is crucial. By sharing your experiences and contributing to research, you are directly impacting the development of treatments and therapies for those affected by mtARS.

Types of Research

Natural History Research

This type of study helps doctors learn how a disease usually behaves by carefully observing people with the condition over time.

CureARS MAPS Registry

A patient registry created in collaboration with NORD on the IAMRARE® platform is a global resource that will provide data for researchers to use to advance drug development and treatment options and to help improve mtARS patient care.

Animal Models

Animal models are essential to mtARS research as they help scientists understand the disease, test potential treatments safely, and develop crucial research tools, ultimately accelerating the path towards effective therapies and a cure.

Preclinical Assets

Zebrafish at Children's Hospital of Philadelphia (CHOP)
C. Elegans Worms at CHOP
Yeast Models (FARS2 & AARS2) at Perlara Labs

Cellular Models

Cellular models provide a simplified yet valuable system for studying the underlying cellular and molecular mechanisms of mtARS disorders, enabling researchers to investigate disease processes and test potential therapies in a controlled and efficient manner.

Preclinical Assets

Fibroblasts at Children's Hospital Colorado and CHOP
Other cell models (iPSCs) at CHOP and Children's Colorado

Drug Repurposing

Drug repurposing offers a significant advantage in drug development by leraging existing safety and efficacy data from previously approved drugs, accelerating the translation of research findings into effective treatments for conditions like mtARS disorders.

Title: Mechanistic and Therapeutic Modeling in ARS2 Class of Primary Mitochondrial Disease in C. elegans and zebrafish animal models.Institution: Children's Hospital of Philadelphia (CHOP)

Awarded: October 2022

Duration: 3 Years

Disease Biomarkers

A reliable disease biomarker for mtARS would revolutionize patient care by enabling earlier and more accurate diagnosis, facilitating personalized treatment plans, and allowing for effective monitoring of treatment response, ensuring that therapies are indeed improving patient outcomes.

Title: Using proteomics to diagnose ARS2 disorders

Institution: Children's Hospital Colorado in collaboration with the University of Melbourne

Awarded: July 2023

Duration: 2 years

Funded Projects

Mechanistic and Therapeutic Modeling in ARS2 Class of Primary Mitochondrial Disease in C. elegans and zebrafish animal models

Principal Investigators:

Marni Falk, MD

Institution/Division:

Children's Hospital of Philadelphia (CHOP)

Direct Cost Requested:

$320,459 over 3 years

Date Awarded:

October 2022

Objective: The overall goal of this project is to identify common pathophysiologic mechanisms and lead
therapeutic candidates with common efficacy across the class of ARS2-based primary mitochondrial disease. The team will use a “therapeutic cross-training” multiple species model organisms study approach, using C. elegans (worms, invertebrates) and D. rerio (zebrafish, vertebrates), to (1) identify mechanistic problems on mitochondrial function and overall animal health that occur from loss of function in this class of genes due to gene knockdown or CRISPR-Cas9 based gene knockout, and (2) prioritize drug compounds to ameliorate mitochondrial dysfunction and improve animal health. Using translational model organisms to investigate the ARS2 class of genes as a group is possible due to the extensive sequence homology conserved between humans, worms, and zebrafish. Importantly, promising therapeutic leads identified in translational research studies can be readily evaluated in human ARS2 disease subjects through the robust precision clinical research initiative and framework that has been developed in the CHOP MMFP.

Learn More

Using proteomics to diagnose ARS2 disorders

Principal Investigators:

Johan L.K. Van Hove, MD, PhD, MBA

David Stroud, Dr. rer. nat.

Institution/Division:

University of Colorado

University of Melbourne

Direct Cost Requested:

$214,000 over 2 year

Date Awarded:

July 2023

Objective:

Characterize the sensitivity of detecting mitochondrial functional abnormalities in fibroblasts from patients with ARS2 defects using a mitochondrial proteomics-based approach.

Future Directions of Research

Gene Therapy

Gene Editing

Biobank

What is Gene Therapy?

Gene Therapy is a promising approach for treating genetic disorders, including those affecting mitochondrial diseases. The aim of gene therapy is to correct the the underlying genetic defect causing a disease. It involves introducing genetic material (DNA or RNA) into a patient's cells.

How Might This Research apply to Mitochondrial ARS Genes?

Mitochondrial Amionacyl-tRNA synthetases (mtARS) are crucial enzymes involved in protein synthesis within the mitochondria. Mutations in these genes disrupt mitochondrial function, leading to severe neurological and developmental disorders.

Potential Approaches:

Gene Replacement: Deliver a healthy copy of the mutated mtARS gene into the patient's cells. This could involve using a modified virus (like an adeno-associated virus - AAV-9)

What is Gene Editing?

Gene Editing aims to alter the existing genetic code within a cell.

Gene editing holds significant potential for treating autosomal recessive conditions like those affecting mitochondrial ARS genes. Here's how:

In autosomal recessive disorders, both copies of a gene must carry a mutation for the condition to manifest.
Individuals with one mutated copy are carriers but typically do not display symptoms.

Gene Editing Strategies:

Correcting the Mutation: Gene editing tools like CRISPR-Cas9 can be used to precisely repair the mutated DNA sequence in both copies of the gene. This can restore the gene's normal function.
Introducing a Functional Copy: If direct correction is challenging, gene editing can be used to introduce a healthy copy of the gene into the genome.

Specific to mtARS Genes, gene editing could:

Correct the specific mutations in the mtARS genes.
Restore normal mitochondrial function.
Alleviate the symptoms of associated disorders.

What is a Biobank?

A Biobank is a collection of biological samples (like blood, tissue, or DNA) and the associate health information of the individuals, stored for research purposes. This is a valuable resource for medical research. These samples and data are stored and managed in a secure and ethical manner, allowing scientists to:

Uncover the mysteries of diseases: By study samples from many people, researchers can better understand how diseases like mtARS develop and progress.
Develop new treatments: Biobanks provide the raw materials for groundbreaking researcher, helping scientists discover new medications, therapies, and diagnostic tools.
Advance personalized medicine: By analyzing individual genetic makeup and health information, researchers can tailor treatments to the specific needs of each patient.

In simpler terms: Biobanks are like special libraries that store valuable pieces of ourselves to help scientists unlock the secrets of health and disease, ultimately leading to better treatments and a healthier future for everyone.

Gene Therapy campaign

Initial Fundraising Goal: $500,000

Identify and Define Patient Population: The first step to a cure, is to identify patients living with an ARS gene mutation. Researchers need to understand how the disease effects these patients now and over time.
Create disease models of ARS Genes: To better understand ARS genes, researchers create models of the genes in animals or using patient cells. These models include mice, zebrafish, worms, and iPSCs.
Study disease models of ARS Genes: Researchers can study disease models to better understand how ARS genes effect the body and how to treat these conditions.

Test potential treatments: Potential treatments can be tested in ARS disease models prior to giving the treatment to a patient. These treatments can include new drugs/therapies, repurposed drugs, or potential cures, such as a gene therapy. Before treating a patient with a potential therapy, researchers are required to prove a drug first works in an ARS disease model.
Involve Patients: Patient involvement is critical to advance research. Due to a small patient population, every patient involved is vital to our success. Opportunities to join patient registries, biosample donations, clinical trial involvement, or participation in data collection may be available.

Overview of Research

Advancing Research

Types of Research

Natural History Research

This type of study helps doctors learn how a disease usually behaves by carefully observing people with the condition over time.

CureARS MAPS Registry

A patient registry created in collaboration with NORD on the IAMRARE® platform is a global resource that will provide data for researchers to use to advance drug development and treatment options and to help improve mtARS patient care.

Animal Models

Animal models are essential to mtARS research as they help scientists understand the disease, test potential treatments safely, and develop crucial research tools, ultimately accelerating the path towards effective therapies and a cure.

Preclinical Assets

Zebrafish at Children's Hospital of Philadelphia (CHOP)

C. Elegans Worms at CHOP

Yeast Models (FARS2 & AARS2) at Perlara Labs

Cellular Models

Cellular models provide a simplified yet valuable system for studying the underlying cellular and molecular mechanisms of mtARS disorders, enabling researchers to investigate disease processes and test potential therapies in a controlled and efficient manner.

Preclinical Assets

Fibroblasts at Children's Hospital Colorado and CHOP

Other cell models (iPSCs) at CHOP and Children's Colorado

Drug Repurposing

Drug repurposing offers a significant advantage in drug development by leraging existing safety and efficacy data from previously approved drugs, accelerating the translation of research findings into effective treatments for conditions like mtARS disorders.

Sponsored Research Project with Children's Hospital of Philadelphia

Title: Mechanistic and Therapeutic Modeling in ARS2 Class of Primary Mitochondrial Disease in C. elegans and zebrafish animal models.Institution: Children's Hospital of Philadelphia (CHOP)

Awarded: October 2022

Duration: 3 Years

Disease Biomarkers

A reliable disease biomarker for mtARS would revolutionize patient care by enabling earlier and more accurate diagnosis, facilitating personalized treatment plans, and allowing for effective monitoring of treatment response, ensuring that therapies are indeed improving patient outcomes.

Sponsored Research Project with Children's Colorado

Title: Using proteomics to diagnose ARS2 disorders

Institution: Children's Hospital Colorado in collaboration with the University of Melbourne

Awarded: July 2023

Duration: 2 years

Funded Projects

Mechanistic and Therapeutic Modeling in ARS2 Class of Primary Mitochondrial Disease in C. elegans and zebrafish animal models

Using proteomics to diagnose ARS2 disorders

Future Directions of Research

Gene Therapy campaign

Initial Fundraising Goal: $500,000

Support Gene Therapy

Leave a one-time donation

Overview of Research

Advancing Research

Types of Research

Natural History Research

This type of study helps doctors learn how a disease usually behaves by carefully observing people with the condition over time.

CureARS MAPS Registry

​A patient registry created in collaboration with NORD on the IAMRARE® platform is a global resource that will provide data for researchers to use to advance drug development and treatment options and to help improve mtARS patient care.

Funded Projects

Mechanistic and Therapeutic Modeling in ARS2 Class of Primary Mitochondrial Disease in C. elegans and zebrafish animal models

Future Directions of Research

Gene Therapy campaign

Initial Fundraising Goal: $500,000

Support Gene Therapy

Leave a one-time donation

A patient registry created in collaboration with NORD on the IAMRARE® platform is a global resource that will provide data for researchers to use to advance drug development and treatment options and to help improve mtARS patient care.