Genomic Medicine and Gene Therapy

Genomic Medicine

  • Definition: The use of genomic information in clinical care.

Personalized Medicine

  • Precision Medicine:
      - In 2011, a report from the National Academy of Sciences called for "precision medicine."
      - This approach involves the integration of genomic, epigenomic, and environmental data to assist in diagnosis.

  • Genomic Medicine:
      - A subset of precision/personalized medicine that uses specific genetic information for clinical applications.

Polygenic Risk Score

  • Definition: A metric that indicates how a person’s risk for a disease compares to the risk of others.

  • Genomic Variants:
      - Minor differences in DNA between individuals.
      - Each person can possess approximately 4-5 million genomic variants.
      - Some of these variants can either increase or reduce a person’s risk of developing certain diseases, while others have no known effect.

  • Disease Association:
      - Diseases can be caused by a single gene or by multiple genes, termed polygenic.
      - Example of polygenic disease: Coronary artery disease is a complex disease influenced by multiple genetic factors.

  • Visualization:
      - Individuals at risk for coronary artery disease may have genomic variants represented by:
        - Red "v" symbols indicating variants associated with the disease.
        - Smaller gray "V" symbols indicating other variants present in the genome but not linked to the disease.
      - About 60 specific genomic variants exhibit a strong association with coronary artery disease.

Polygenic Risk Score Calculation

  • Determination Process:
      - Involves comparing the genomes of individuals with the disease to those without it.
      - Diseases may show hundreds to thousands of associated variants.
      - Computational methods and statistical tests evaluate an individual's specific variants to calculate risk for a condition.
      - Limitations: Does not account for environmental factors or other non-genomic influences on health.

Applications of Genetics in Medicine

Prenatal Testing

  • Overview: Prenatal testing is commonly available.

  • Method: Isolation of placental DNA fragments from maternal blood for analysis.

  • Purpose: Detection of chromosomal abnormalities.

Gene Therapy

  • Definition: A medical approach that employs genes to treat, prevent, or cure disorders.

  • Applications:
      - Introduction of new copies of a defective gene.
      - Replacement of a missing or impaired gene.

Research & Innovation

Case Studies: Gene Therapies for Sickle Cell Disease

  • Recent Advances:
      - The therapies Casgevy and Lyfgenia have received approval for the treatment of sickle cell disease (noted by Carrie MacMillan, December 19, 2023).

  • Comparison:
      - Traditional treatment involved bone marrow transplants.
      - Distinct Mechanisms:
        - Lyfgenia uses a viral envelope to introduce a functional hemoglobin-producing gene.
        - Casgevy modifies an existing gene to stimulate the production of fetal hemoglobin.

  • Cost and Duration:
      - Treatment is approximately $2-3 million per patient and takes about one year to administer.

Gene Therapy for Hemophilia B

  • Condition Overview: Hemophilia is a genetic disorder that impairs the body’s ability to form blood clots, leading to spontaneous bleeding episodes.

  • Treatment:
      - Administered as a single dose of gene therapy.
      - Allows the liver to produce clotting factor IX, essential for normal blood clotting function.

  • Results:
      - One year post-treatment, patients observed a 71% reduction in bleeding frequency, with over 50% experiencing no bleeding incidents at all.

  • Regulatory Approval: The therapy received FDA approval in April 2024, based on these study outcomes (announced September 25, 2024).