Research for Individualized Therapeutics in Rare Genetic Disease

Study Overview
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Brief Summary
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The purpose of this research study is to identify individuals that have a rare genetic disease without an adequate therapeutic strategy that might be treatable with drug developed to target the disease-causing genetic alteration.

Official Title
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Research for Individualized Therapeutics in Rare Genetic Disease

Conditions
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Rare Genetic Disease, Undiagnosed Diseases

Intervention / Treatment
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* Other: Individualized drug matching per genetic disease


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has Mayo Clinic or other medical health system ID, or another unique identifier. Able to provide informed consent. Individual must have evidence of a genetic disorder as determined by a provider or genetic counselor with causative or likely causative genetic variants identified by molecular testing. Genetic variants must be hypothesized to be targetable using antisense oligonucleotide drugs (such as: knockdown gain of function alterations, increase protein production for reduced function alterations, or modulate mRNA splicing to correct abnormal splicing, promote normal splicing, or return reading frame to an out-of-frame transcript to restore function, etc.) based on current acceptable understanding of ASO mechanisms of action and tissue/organ targeting efficiency. Biological family member of an enrolled individual. Would be able to travel to a Mayo Clinic site for ongoing treatment should a therapeutic be developed. Treatment at the individual's current disease state would likely provide benefit based on current clinical data and understanding of the progression of the disease. -Or- Biological family member of an enrolled individual Able to provide informed consent or has a LAR available to provide informed consent Exclusion Criteria Individuals who have situations that would limit compliance with the study requirements. Institutionalized (i.e. Federal Medical Prison).
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Rare genetic disease individualized drug development screening candidate<br>Patients with targetable disease-causing genetic alterations will be evaluated on a case by case basis. The research study will utilize biospecimens to determine if an individualized therapeutic may be developed as a possible treatment option. If an individualized therapeutic drug can be developed, a future IND FDA application (n=1) will be filed. | Other: Individualized drug matching per genetic disease<br>* Patient phenotype and samples will be evaluated for individualized therapeutic drug development<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Enrollment of study participants | To recruit and enroll participants with a confirmed rare genetic disease whose genetic variants may be targetable by an ASO and/or other drug. | 5 years | 
| Collection of biospecimens | Total number of biopecimens collected which may include blood samples, skin biopsy and fibroblast culture, organ biopsy specimens | 5 years | 
| Partnered research with external entities | To engage in partnered research with external entities (foundations, academia, and drug companies) to facilitate the ASO and/or other drug development and testing. | 5 years | 
| Future IND applications | To submit an IND application with the FDA following successful drug development and safety/toxicity testing outcomes. | 5 years | 
| Determine natural history and clinical baseline | To determine the natural history and clinical baseline of patient's disease status. This will be used to determine efficacy when treated with experimental ASO and/or other drug. | 5 years | 
| Determine individualized therapeutic efficacy | To determine clinical efficacy of treatment with experimental ASO and/or other drug. | 5 years | 
| Publish findings | To publish and/or share findings to improve patient specific ASO and/or other drug development and increase the number of therapeutic options for individuals with rare genetic disease. | 5 years |