Cell and Gene Therapy
- stephenbeesley2
- 8 hours ago
- 4 min read
By Stephen Beesley
What is Cell and Gene Therapy?
Cell and gene therapy (CGT) are advanced medical approaches that can treat a variety of diseases that derive from an underlying genetic dysfunction (could be either DNA or RNA). Gene therapy delivers genetic material (DNA or RNA) into a patient’s cells to correct or compensate for faulty genes, often using viral vectors such as adeno-associated virus (AAV) and lipid nanoparticles (LNP). This kind of therapy aims for a one-and-done approach, so that there is no continued therapy as there would be with a pill or tablet. Cell therapy involves administering living cells (stem cells or engineered immune cells), often taken from the patient to avoid an immune response/rejection, to restore or modify tissue function. Together, these therapies aim to address the root causes of disease rather than to treat symptoms. They are transforming treatment options for genetic disorders, cancers, and neurodegenerative diseases, offering the potential for long-lasting, even curative outcomes, as once the DNA of a cell has been changed, it will remain that way for the life of that cell, and the modification will be passed on to any daughter cells if/when the original 'mother' cell divides.
What did we see in 2025?
2025 saw both highs and lows for the CGT landscape, with an FDA approval for Zevaskyn from Abeona Therapeutics. Zevaskyn is a therapy for Recessive Dystrophic Epidermolysis Bullosa (RDEB) and uses genetically corrected skin cells to heal chronic wounds. Also approved by the FDA was Waskyra from Fondazione Telethon ETS (an Italian non-profit). This is the first cell-based gene therapy for Wiskott-Aldrich Syndrome (WAS), a genetic immune deficiency, and approved for pediatric and adult patients. There was mixed news in the neurodegenerative space as therapeutic intervention for Huntington's Disease (HD) gained positive news, showing clinical trial data reported by UniQure, stating that its gene therapeutic candidate, AMT-130, reduced the progression of Huntington symptoms by 75% over a 3-year study in 12 people versus a comparison group. This was fantastic news, given that the disease is 100% fatal and that the mutated gene (called Huntingtin) is often passed on to children before a positive diagnosis in the parent. However, within weeks of this announcement, the FDA reversed its guidance on the accelerated approval of AMT-130, citing that the control group was insufficient to support an approval filing based on the phase 1/2 data. This was a huge upset to the HD community, particularly as the FDA had given the trial a green light in earlier meetings. This reversal highlights the uncertainty and apprehension of the FDA surrounding gene therapy candidates, especially in trials with a small number of patients. This could have more severe consequences within the rare disease space, as patient numbers are inherently low; therefore, sufficient clinical trial enrolment will be hard to navigate and manage. New thinking around trial design will be needed, and more thorough/stable guidance from the FDA will be required.
There were also several other cell therapy approvals during 2025, slightly less than in 2024 likely coinciding with updated FDA guidelines on safety and balancing the speed of innovation with positive patient outcomes. Encelto from Neurotech Pharmaceuticals was approved in March 2025. This is a cell therapy implant for macular telangiectasia type 2 (a gradual progressive eye disease), delivering ciliary neurotrophic factor (CNTF) for photoreceptor protection. Another notable approval was Breyanzi (Bristol Myers Squibb/Juno). This therapy was approved late in the year (December 2025) as the first CAR-T (Chimeric Antigen Receptor T)-cell therapy for marginal zone lymphoma, and with it expanding cell therapy into the oncology space.
The Negative Side of Gene Therapy in 2025
Together with the good and positive side of gene therapy, there comes along some negative news. Sadly, there were several mortalities associated with a number of potential therapies. I have listed a few here for reference, but it is by no means an exhaustive list.
Sarepta Therapeutics saw three deaths. Two were pediatric patients using Elevidys (used to treat Duchenne muscular dystrophy or DMD). A third was an adult patient enrolled in a clinical trial for Limb Girdle Muscular Dystrophy (LGMD). Both treatments involved the use of an adeno-associated virus (AAVrh74), and the deaths were attributed to liver toxicity. The FDA requested a voluntary suspension of Elevidys and put the clinical trials on hold.
A patient in the Magnitude clinical trial by Intellia Therapeutics died from liver toxicity, leading to a pause in the trial. This trial was designed to treat patients with heart failure due to transthyretin amyloidosis with cardiomyopathy (ATTR-CM). This was a therapy designed to inactivate the transthyretin (TTR) gene in liver cells, but in this case the delivery method was not a virus but LNP.
Capsida Biotherapeutics was also in the headlines due to the death of a pediatric patient in a trial for STXBP1 encephalopathy, a rare condition characterized by abnormal brain function (encephalopathy) and intellectual disability. The trial used AAV as the delivery method to gain access to the brain. The death was reported as cerebral edema (brain swelling). The trail was stopped immediately.
Conclusion
Whilst gene therapy has been around for the best part of three decades, with the first successful treatment in 1990 and with the subsequent development of CRISPR-CAS9 in 2012, the science may be well placed and capable of providing the treatment needed (often niche) for many genetic conditions that affect the population; however, it appears that we are still very much in the early stages when it comes to delivery methods and mechanisms. We have the technology to get genetic treatments into the body and to deliver them to specific organs, yet, unfortunately, we are now discovering their unwanted side effects. Long before clinical trials, therapies are extensively tested on human-derived cells, rodents and non-human primates (NHP; monkeys) models. Only after considerable toxicity evaluations are the therapies allowed into humans trials. However, even though very close genetically, humans are not monkeys and key differences can come rapidly to light once human trials begin. Therefore, more thorough planning and preparation are needed, and most likely a thorough re-evaluation of how we transition from animal work to human trials, if we are to continue to advance CGT safely and effectively.
References
https://www.clinicaltrialsarena.com/news/capsida-biotherapeutics-gene-therapy-patient-death/?cf-view
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