The Impact of Genetic Testing on Rare Disease Treatments

Genetic testing plays a critical role in the diagnosis and treatment of genetic disorders. It not only confirms diagnoses but also identifies specific genetic variants that are essential for determining a patient’s eligibility for certain therapies. This information is crucial for developing effective treatment strategies and understanding rare genetic conditions. Our latest Community Quick Takes module explores the role of genetic testing in Duchenne muscular dystrophy (DMD), giant axonal neuropathy (GAN), and Angelman syndrome.

How Genetic Testing Informs Duchenne Muscular Dystrophy

For those with Duchenne muscular dystrophy, genetic testing can reveal specific mutations in the DMD gene that may impact treatment eligibility. Research shows that deletions affecting exons 8 through 11 of the DMD gene are highly immunogenic, meaning these mutations are likely to trigger an immune response. As a result, current gene therapy trials or approved treatments often exclude patients with mutations in these exons.

Additionally, some trials exclude patients with mutations in exons 1 through 17 to avoid potential immune complications. However, future research may incorporate immune-modulating drugs, expanding access to gene therapy for a broader range of patients.

The Role of Genetic Testing in Giant Axonal Neuropathy

In the case of giant axonal neuropathy (GAN), genetic testing is crucial for understanding the immune risks associated with gene therapy. Specific genetic profiles may increase a patient's risk of rejecting the newly introduced genetic material. By identifying these risks through genetic testing, doctors can design immune suppression protocols to prevent rejection and improve the likelihood of successful treatment.

Immune modulation strategies, based on the patient’s genetic information, can help mitigate these risks, paving the way for more effective gene therapies for GAN.

Genetic Testing and Emerging Therapies for Angelman Syndrome

Angelman syndrome, caused by defects in the UBE3A gene, offers another example of the power of genetic testing. The disorder can result from various changes in the UBE3A gene, leading to a lack of UBE3A protein production. Researchers are exploring the use of antisense oligonucleotides (ASOs) to treat Angelman syndrome by “un-silencing” the paternal UBE3A copy, potentially restoring protein production in patients with a defective maternal gene.

Genetic testing is essential to ensure the therapy is safe and effective. Overexpression of the UBE3A protein could lead to harmful effects, so careful consideration and genetic monitoring are necessary to avoid complications.

For many rare diseases or disorders genetic testing is a powerful tool that guides treatment decisions and can help avoid immune complications when receiving a gene therapy. As research on potential therapies continue to evolve, genetic testing will remain a vital component in ensuring that patients receive the most effective and personalized care.

Alexis is ASGCT's Patient Outreach Manager.

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