A Deaf Person Can Hear Now: A Notable Success with Gene Therapy

Genetic interventions by genotyping to improve physical functionality are no longer far-fetched.

Our genes fascinate me, so I have a strong interest in genetics, especially from practical angles like performance improvement and its potential to cure incurable diseases or lack of functionality, such as deafness or blindness. I study genotyping and genetic interventions to gain insights into possibilities, especially in enhancing cognitive performance. However, it is a very complex and comprehensive discipline with ethical implications.

In this post, I focus on genetic intervention, which refers to the deliberate manipulation or alteration of an organism’s genetic material using various techniques to modify specific traits or treat genetic disorders. Updated Onim Gene Map Statistics inform that 7,503 genetic disorders have been reported, and more are constantly being described.

There are three main strategies for gene therapy: gene editing, gene replacement, and gene suppression. This book chapter categorizes genetic diseases into three types according to their causes: monogenic disorders, chromosomal disorders, and multifactorial disorders.

In this post, first, I provide a high-level perspective and background on genotyping and genetic interventions. Then I summarize the key points of a 2023 paper about treating hereditary hearing loss with ongoing clinical trials and introduce a specific achievement (recovery of deafness) in gene therapy mentioned in the media early this year.

What does genotyping mean in simple terms?

Genotyping is the process of determining our genetic makeup by analyzing our DNA. This analysis involves identifying specific variations or mutations in the DNA sequence, known as genetic markers, associated with particular traits, diseases, or conditions.

Genotyping is a valuable tool in various fields, including medical genetics, pharmacogenomics, evolutionary biology, and forensic science. Standard techniques used in genotyping include polymerase chain reaction (PCR), microarray analysis (MA), and next-generation sequencing (NGS).

PCR is a lab technique for amplifying a specific DNA segment through repeated heating and cooling cycles.

MA is a high-throughput method that allows the simultaneous detection and quantification of many DNA sequences or gene expression levels in a single experiment.

NGS enables rapid and cost-effective sequencing of large stretches of DNA, facilitating the analysis of entire genomes with high accuracy and throughput.

The Promise of Genetic Interventions with Genotyping Aimed at Enhancing Physical Functionality

Genetic interventions aimed at enhancing physical functionality are no longer confined to science fiction but are increasingly becoming a tangible reality. With advancements in genetic engineering technologies, scientists can now precisely edit genes associated with physical attributes and capabilities.

For instance, researchers have explored modifying genes related to muscle growth and endurance to enhance athletic performance potentially. By targeting specific genes involved in muscle development, scientists aim to augment muscle mass and strength, potentially offering athletes a competitive edge.

This 2022 paper informs that nearly 200 genetic polymorphisms have been found to influence sports performance traits, and over 20 polymorphisms may condition the status of the elite athlete.

However, with the current evidence, it is too early to determine how genotyping can be used to predict exercise/sports performance or improve current training methods. Research on this topic presents methodological limitations.

Genetic interventions hold promise in addressing inherited disorders like deafness or blindness and conditions that limit physical functionality. Diseases like muscular dystrophy, which affects muscle strength and mobility, could be treated through gene editing techniques to correct the underlying genetic mutations responsible for the condition.

By repairing or replacing faulty genes, scientists envision restoring normal muscle function and improving overall physical capabilities in affected individuals. This transformative approach offers hope for people living with genetic disorders, potentially alleviating their symptoms and enhancing their quality of life.

However, the ethical implications and societal consequences of genetic interventions to enhance physical functionality remain subjects of intense debate. Questions surrounding fairness, equity, and unintended consequences arise as genetic enhancements blur the lines between therapy and enhancement.

Concerns about creating a genetic divide between those who can afford enhancements and those who cannot, as well as the potential for unintended side effects or unforeseen consequences, highlight the need for careful consideration and regulation of genetic interventions.

Insights from the Literature on Treating Hereditary Hearing Loss

Genetic studies started in the 1860s. For example, Mendel conducted experiments with pea plants and discovered the basic principles of heredity. Before Mendel, genetics was primarily theoretical, while after Mendel, the science of genetics was broadened to include experimental genetics. Currently, Pubmed indexes over 5 million reports.

Rather than going into theoretical details, I want to summarize the findings of a 2023 study published on Molecular Therapy to give you an idea of how to treat deafness using gene therapy. This comprehensive paper also outlines previous research.

The paper “Advances in gene therapy hold promise for treating hereditary hearing loss” is comprehensive and complex, so I will summarize its key points in simple terms. It is also educational and provides details for those who want to learn about various approaches to gene therapy.

The paper addresses three main gene therapy strategies: gene replacement, gene suppression, and gene editing.

It summarises the most appropriate strategy for particular monogenic (single-gene) diseases based on different pathogenic (disease-causing) mechanisms.

Then, it focuses on its successful applications for hereditary hearing loss in preclinical trials. It also elaborates on the challenges and outlooks of gene therapy for this condition.

Gene therapy aims to fix hearing problems by targeting faulty genes related to deafness. It uses three methods: replacing, suppressing, or editing. Each method is chosen based on the specific genetic issues causing deafness.

For recessive disorders, both gene copies are faulty, while dominant disorders have more complex causes: loss-of-function (one copy doesn’t work), dominant-negative (mutant copy disrupts normal function), and gain of function (mutant copy boosts gene activity).

In terms of clinical trials treating hereditary hearing loss, particularly caused by mutations in the OTOF gene, three clinical trials are currently underway.

These trials, conducted by Akouos, Decibel Therapeutics, and the project by the owners of this 2023 study, aim to introduce functional otoferlin protein into the inner ear using gene therapy.

Akouos’ AK-OTOF and Decibel’s DB-OTO have received FDA approval for clinical trials. AK-OTOF, delivered via the round window membrane (RWM) with oval window fenestration, has shown promising results in preclinical studies and will soon undergo phase 1/2 trials in children.

DB-OTO, also targeting otoferlin expression, has demonstrated improvements in auditory function in preclinical studies and will include infants under two years old in its trial.

The candidate for the owners of this study, RRG-003, has effectively restored hearing in mice and will undergo clinical trials using minimally invasive endoscopic inner ear administration via RWM, starting with patients aged 3–10 years.

An 11-Year-Old Boy Experiences Hearing for the First Time

According to CBS News, on 25 January 2024, the Children’s Hospital of Philadelphia shared a significant development in the life of 11-year-old Aissam Dam from Spain, who was born deaf.

Following treatment at the hospital in October 2023, he became the inaugural person to undergo gene therapy in the U.S. for congenital deafness.

Conducted as part of a trial supported by Akouos, a subsidiary of Eli Lilly, the hospital disclosed that this 11-year-old boy had begun perceiving sounds for the first time. Although the sounds are muted, resembling the sensation of wearing foam earplugs, he can now discern his father’s voice and traffic on the road.

My deaf friend, Joellyn Rose Keener, wrote a story about it last week.

This story meant a lot to me as I worked with many deaf people and learned about their challenges. I wrote a tribute to one of my deaf friends who lived for 100 years and died on New Year’s Eve of 2022. Jeremy has always desired to hear since his childhood, like his siblings.

Conclusions and Takeaways

The journey toward genetic interventions for improving physical functionality reflects the remarkable progress in genotyping and gene therapy techniques.

Through gene replacement, gene suppression, and gene editing strategies, researchers aim to correct underlying genetic mutations responsible for various disorders, including deafness.

While the successful trials conducted by Akouos, Decibel Therapeutics, and other institutions demonstrate promising outcomes, they also highlight the importance of continued research, ethical considerations, and regulatory oversight in genetic interventions.

The successful treatment of 11-year-old Aissam Dam through gene therapy offers hope and potential solutions for people with genetic disorders affecting hearing.

As genetic interventions become increasingly sophisticated and accessible, they hold promise for restoring sensory functions and addressing various genetic diseases and physical limitations.

As we continue to explore the possibilities and implications of genetic interventions, it is essential to prioritize ethical principles, accessibility, and inclusivity to ensure that these advancements benefit humanity.

The journey toward genetic interventions has many challenges. However, it offers unprecedented opportunities to rewrite the narrative of genetic diseases and redefine what it means to live with genetic conditions.

Thank you for reading my perspectives. I wish you a healthy and happy life.

To inform my new readers, I wrote numerous articles that might inform and inspire you. Some of my topics include brain, mental health, cognitive function, significant health conditions, longevity, nutrition/food, valuable nutrients, ketogenic lifestyle, self-healing, weight management, writing/reading, and humor, including 100+ Insightful Life Lessons from My Circles for the Last 50+ Years.

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