Genetic Fix or False Hope? The Reality of Gene Therapy in Rare Conditions

The Rare360 Editorial Team
Aug 11
8 min read

Updated: Aug 12

DNA strand and virus particle in a lab, with a spark indicating interaction; blue and orange colors dominate the scene.

Introduction: A New Era of Genetic Medicine

For millions of individuals and families affected by rare genetic conditions, gene therapy has emerged from the pages of science fiction into clinical reality. No longer a distant promise, this approach—aiming to correct, replace, or edit defective genes—has rapidly expanded from niche experimental interventions into a high‑growth, high‑stakes industry projected to reach over $25 billion in global market value by 2025, rising to $118 billion by 2034.

In 2025 alone, more than 22 gene and cell therapies have secured FDA approval for conditions ranging from hemophilia B and cerebral adrenoleukodystrophy to severe skin disorders (RDEB), marking a new era of possibilities for rare disease patients.

Yet, beneath these advances lie a complex landscape of clinical uncertainty, safety worries, and ethical challenges. Take Elevidys, Sarepta’s gene therapy for Duchenne muscular dystrophy (DMD), initially approved in 2023. Several non-ambulatory patients experienced fatal liver failure, prompting an FDA-imposed halt on shipments to vulnerable groups.

Although the hold was later lifted for ambulatory patients, questions about risks, trial inclusion, and regulatory oversight persist.

This article goes beyond headlines to explore whether gene therapy is truly a genetic fix—or a false hope—for rare disease communities. It aims to empower patients, caregivers, and advocates to understand what’s emerging, who benefits, and what must be done to ensure innovation equals inclusion.

What Is Gene Therapy?

Gene therapy is an innovative medical approach that aims to treat diseases at their source by correcting or replacing the underlying genetic defects. For people living with rare genetic disorders, many of which are caused by a single faulty gene, this form of treatment holds the potential to address the root cause, not just manage symptoms.

Different Approaches to Gene Therapy

There are three main strategies gene therapy can use:

Gene Replacement

How it works: A healthy copy of a gene is inserted to replace a faulty one.
Where it applies: Often used for inherited disorders caused by a single defective gene, such as certain forms of blindness or spinal muscular atrophy.
Example: Zolgensma replaces the missing SMN1 gene in spinal muscular atrophy (SMA) patients to help produce a crucial motor neuron protein.

Gene Editing

How it works: Technologies like CRISPR-Cas9 allow scientists to cut out or repair the defective segment of DNA directly within a patient’s genome.
Promise and potential: This method is lauded for its precision and adaptability. It can potentially “edit” a wide range of mutations that cause rare conditions.
Example: Casgevy (CRISPR-based therapy) edits a gene in patients with sickle cell disease, enabling the production of healthy red blood cells.

Gene Silencing or Suppression

How it works: Turning off a harmful gene to prevent it from causing damage.
Example: Experimental therapies for Huntington’s disease aim to reduce the toxic protein levels caused by mutated genes.

How Is It Delivered?

Most gene therapies are delivered using a viral vector, a modified virus that acts like a tiny delivery truck, carrying the therapeutic gene into the body’s cells. Common vectors include:

Adeno-Associated Virus (AAV) – used in many rare disease treatments due to its safety record.
Lentivirus – often used in blood-related conditions, such as inherited immune or blood disorders.
CRISPR-Cas9 – a newer method that can cut and correct genes inside the cell.

Why Gene Therapy Is Particularly Relevant to Rare Conditions?

Most rare diseases are “monogenic,” i.e., they stem from mutations in a single gene. This makes them ideal candidates for gene therapy, as a one-time treatment could potentially stop the progression of the disease rather than merely palliating symptoms. Recent clinical successes, such as those seen with therapies for inherited blindness and spinal muscular atrophy, have demonstrated that these targeted approaches can result in dramatic improvements in quality of life. However, while early results are promising, researchers and regulatory bodies continue to monitor the long-term safety and durability of these treatments.

Real-World Impact: Where Gene Therapy Has Made a Difference

For many individuals and families affected by rare diseases, gene therapy represents more than a scientific breakthrough—it’s a long-awaited lifeline. While still a relatively new field, there have been remarkable early successes that demonstrate the life-changing potential of these therapies.

Success Stories that Inspire Hope

Zolgensma for Spinal Muscular Atrophy (SMA)
Perhaps the most well-known gene therapy success to date is Zolgensma, approved by the U.S. FDA in 2019 for children under 2 years old with SMA—a rare genetic disease that leads to progressive muscle weakness. Zolgensma delivers a functional copy of the SMN1 gene, helping halt or significantly slow disease progression. In many cases, children treated early are now sitting, crawling, or walking—milestones that were previously thought unattainable.
Abeona’s Zevaskyn for RDEB
In April 2025, the FDA approved Zevaskyn (pz‑cel), the first cell-based gene therapy for Recessive Dystrophic Epidermolysis Bullosa (RDEB)—a painful skin disorder caused by COL7A1 mutations. The therapy uses healthy skin cells engineered with functional COL7A1 and grafted back onto patients. Clinical trials show significant wound healing and pain reduction, though the treatment is priced around $1.75 million per round.
Casgevy (exagamglogene autotemcel) for Blood Disorders
Casgevy, a CRISPR-based gene-editing therapy for sickle cell disease and β-thalassemia, became the first of its kind to reach patients. It was approved in December 2023 by the FDA and earlier by the UK’s MHRA. While the treatment process is complex—including stem cell collection, chemotherapy, gene editing, and transplant—it has delivered lasting relief: many treated patients remain free of pain crises and transfusion requirements months after therapy.
Roctavian & Hemgenix: Hemophilia Gene Therapies
Roctavian (valoctocogene roxaparvovec) for Hemophilia A, FDA-approved in mid‑2023, and Hemgenix (etranacogene dezaparvovec) for Hemophilia B, approved in late‑2022, are one-time gene therapies that enable patients to produce clotting proteins within their liver. These therapies offer freedom from frequent dosing and reduce bleeding episodes, reshaping daily life for people long dependent on regular factor infusions.
Precision Gene Editing for Ultra-Rare Metabolic Disorders
In a landmark early 2025 case, researchers in Philadelphia treated an infant with CPS1 deficiency, a lethal metabolic disorder, using a bespoke CRISPR-based therapy. Tailored with lipid nanoparticles targeting the specific genetic fault, this intervention led to improved biochemical profiles and developmental gains, without needing a liver transplant. Researchers hope this case will herald more rapid, custom-designed treatments for rare disorders beyond the blood-related conditions that currently dominate the pipeline.

The Unmet Needs: Limitations, Risks, and Ethical Concerns

While gene therapy offers profound hope, it is not a universal fix. The reality is that many rare disease patients continue to face significant challenges when it comes to access, safety, affordability, and ethical transparency. As much as we must celebrate the promise of gene therapy, it’s equally important to confront the unresolved issues that surround it.

Scientific and Clinical Limitations

Not a universal solution: Gene therapies often target a single gene, making it feasible for only a subset of rare diseases with known genetic mutations. Many rare conditions have complex or unknown genetic origins, making them poor candidates for current gene therapy models.
Durability of effect: In some cases, gene therapy may not offer a lifelong solution. For example, therapies that use adeno-associated virus (AAV) vectors may not be re-administered due to immune response, and long-term durability remains uncertain for several treatments.
Delivery challenges: Efficient delivery to the right cells or tissues—especially the brain, eyes, or muscles—is complex. Conditions that affect multiple organ systems pose a bigger challenge.

Safety Risks and Adverse Events

There have been serious safety concerns, including recent cases of patient deaths in experimental gene therapy trials, such as Sarepta’s Duchenne Muscular Dystrophy program. While these events are rare, they highlight the need for better oversight and risk communication, especially when working with vulnerable patient populations.

Adverse effects underscore the complexity of modifying the human genome, even with precision tools like AAV or CRISPR-based technologies. Common safety concerns include:

Immune system responses: Some patients have experienced severe immune responses, liver toxicity, or neurological complications. There have even been trial-related fatalities, such as those reported in Sarepta’s Duchenne muscular dystrophy gene therapy programs (2025).
Insertional mutagenesis: Though rare with AAV vectors, there is still a theoretical risk of disrupting other genes or triggering cancer if the inserted DNA integrates into the genome inappropriately.
Informed consent complexity: For families in crisis, especially with pediatric patients, fully understanding the risks can be difficult. Informed consent must evolve to be clearer, culturally sensitive, and accessible

Ethical Questions and Informed Consent

Skyrocketing costs: Treatments like Zolgensma have price tags exceeding $2 million per dose. This raises questions of affordability, insurance coverage, and who gets access—especially in under-resourced countries or underserved communities.
Health equity concerns: Patients from marginalized racial, ethnic, or economic groups are underrepresented in clinical trials and may face additional barriers in accessing gene therapies post-approval.
Regulatory bottlenecks: Slow regulatory approvals, reimbursement delays, and country-specific restrictions can keep life-saving treatments out of reach, even after approval elsewhere.

Advocacy Call: Equity, Transparency, and Accountability

The rare disease community must not only push for innovation, but demand fairness and ethical responsibility in how it’s developed and delivered:

Equitable trial inclusion: Advocacy groups must continue to push for diverse, global representation in clinical trials.
Transparent safety data: Developers must be transparent with adverse event reporting to build trust and make informed decisions possible.
Global access strategies: Regulatory and healthcare systems must collaborate with rare disease organizations to create funding mechanisms, compassionate use programs, and sustainable manufacturing pipelines.

A Future Reimagined: What the Rare Disease Community Needs From Gene Therapy

Gene therapy’s potential can only be fully realized if the rare disease community is not just included, but actively prioritized in research, policy, and implementation. For patients and families who have faced a lifetime of medical gaslighting, misdiagnosis, or invisibility, this technology must be delivered with a commitment to justice, equity, and compassion.

Patient-Centric Research and Trial Design

Community-led input: Patients, caregivers, care partners and sadvocacy organizations must have a seat at the table when trials are being designed. This ensures outcomes measured truly reflect what matters to patients—such as quality of life, not just biomarker improvement.
Diverse recruitment: Clinical trials must be inclusive of patients from various ethnic backgrounds, geographic regions, and socioeconomic statuses. Without this, approved therapies risk being effective only for a narrow segment of the population.
Pediatric considerations: Many rare diseases manifest early in life. Researchers must develop safe and ethically sound protocols for including children in studies while ensuring long-term follow-up.

Affordability and Access

Sustainable pricing models: The current “pay-once, price-in-millions” approach is not sustainable or equitable. Value-based pricing, outcome-based reimbursement, and nonprofit partnerships must be explored.
Global access: Rare disease patients in low- and middle-income countries must not be excluded. International alliances, tech transfer agreements, and local manufacturing partnerships can improve accessibility.
Insurance innovation: Advocacy groups should work with insurers and public health systems to create coverage models that account for the upfront cost but reflect long-term health savings.

Transparency and Trust

Clear safety communication: Transparency around adverse events, long-term follow-up results, and regulatory updates is critical. Patients deserve the full picture, not just the success stories.
Ethical marketing: Gene therapy should not be marketed with exaggerated hope. Advocacy groups must hold companies accountable for honest, balanced communication that supports truly informed decisions.
Accessible education: Materials explaining gene therapy must be understandable, multilingual, and culturally sensitive, particularly for adult patients, caregivers and underserved populations.

Advocacy in Action

Policy reform: Advocates should push for legislative frameworks that incentivize equitable gene therapy development, remove regulatory bottlenecks, and protect patients from predatory pricing.
Data sharing and collaboration: Rare disease researchers, clinicians, and biotech firms must collaborate openly, sharing insights, harmonizing trials, and accelerating safe approvals.
Mental health and psychosocial support: Transitioning into or out of gene therapy trials can be emotionally taxing. Counselling and peer support must be integrated into care models.