Gene Therapy: A Second Chance at Life

8th March 2023 - Last modified 18th October 2023

By Bree Foster PhD, Science Writer

In 2022, a gene therapy called Libmeldy was approved for use in the NHS. Used to treat MLD, a rare congenital disorder, this treatment successfully saved the life of a toddler by genetically modifying her stem cells to prevent the disease from manifesting.

Imagine having a cheeky three-year-old daughter who is full of energy and loves to sing and dance. But then gradually her walking becomes uneven, she keeps falling over, and speaking becomes more difficult for her.    

Nala Shaw was diagnosed with metachromatic leukodystrophy (MLD) in April 2022 [1]. MLD is a rare disease, only affecting roughly 1 in 100,000 people worldwide [2], but one that has devastating consequences.

In MLD, a gene called ARSA is mutated, causing an accumulation of fatty chemicals that gradually destroy the protective layer around the cells in the brain and nervous system. This leads to the loss of acquired motor skills and speech and, eventually, causes death.

For Nala, the symptoms had progressed too far for a cure. But for her little sister, Teddi, there was still hope in the form of gene therapy.

What is Gene Therapy?

It has been over 50 years since visionary scientists proposed the idea of “Gene Therapy,” suggesting that for certain conditions, faulty genes could be replaced or altered to provide a permanent cure for previously untreatable diseases [3]. This concept has now become reality and is being used to save lives. To see more examples of gene therapy in action, check out our blog on how base editing treated Alyssa’s “incurable” cancer.

Worldwide, 24 gene therapies have been approved for medical use, including Libmeldy in the EU and UK [4]. These treatments often target rare diseases and cancers, for which there are no other viable alternatives. Since there are over 10,000 human disorders caused by a mutation in a single gene [4], gene therapy could be a promising solution for thousands of disorders and millions of people. 

Gene therapies can work by several mechanisms [5]:

• Ex vivo: the target cells are removed from the patient’s body, genetically modified to correct the disease, and re-infused to the patient. 

• In vivo: a viral vector containing the tools for targeted genetic modification are administered directly to the patient, usually via the blood stream or spinal fluid.

• In situ: a viral vector containing the tools for targeted genetic modification are administered directly to the patient, but to a specific site e.g., a tumour.

In the case of Teddi Shaw, stem cells were taken from the blood, genetically altered to swap out the harmful gene with a healthy one, and then re-infused back into her body. The healthy version of the gene is capable of producing an enzyme that can then break down the fatty chemicals that are slowly destroying the tissue around the brain and nervous system. Because this treatment prevents rather than treats existing damage, it is crucial to identify the disease early.

Treatment is Only Half the Battle

Gene therapy is a truly revolutionary medicine and will undoubtedly save many lives in the years to come. However, an effective treatment is just half the battle. For many rare conditions, treatment needs to be delivered early to be successful. In the case of Nala Shaw, her MLD wasn’t diagnosed until her symptoms were noticeable and then it was too late to save her. This underscores the necessity for us to improve our screening and diagnostic tools in order to fully utilise medical advancements like gene therapy.

Neonatal screening is essential for early diagnosis, allowing healthcare professionals to adapt their treatment early for both parent and baby, potentially preventing severe disability or fatality in the future. In the UK, newborns are screened for nine rare conditions using a heel-prick test including sickle cell disease, cystic fibrosis, congenital hypothyroidism and six metabolic conditions [6]. Though these conditions are genetic in origin, the test itself does not use genetics but rather identifies specific chemical markers that indicate the presence of disease.

However, there are many rare diseases that are not included in typical neonatal screening programmes including MLD. This can result in diagnosis taking many years, leading to more severe symptoms and making treatment more difficult or impossible. Simply scaling up the current heel-prick test to include hundreds of other diseases isn’t a viable option though, as not all disorders have a signature chemical marker detectable in the blood at the time of the test (five days after birth), or indeed, at any time. 

Instead, a genomic approach may offer the chance to ensure timely diagnosis for a much wider range of rare diseases. Screening in this way would allow for the sequencing and analysis of whole genomes to detect hundreds of potential disease-causing genes. Genomics England is currently planning a pilot project in favour of this goal, offering whole genome sequencing to 100,000 newborns [7]. The programme provides an exciting opportunity to expand UK newborn screening from the nine conditions currently offered to many more rare diseases such as Sanfilippo syndrome and Adenosine deaminase deficiency, both of which significantly impair children.

This is a huge potential transition in neonatal healthcare that could allow for the detection of a much broader range of diseases and prevent cases like Nala Shaw from ever happening again.

References:

(1) BBC News 2023. UK’s most expensive drug Libmeldy saved Teddi Shaw, but is too late for her sister. 15 February. Available at: https://www.bbc.com/news/health-64629680 [Accessed: 1 March 2023].

(2) Lamichhane, A. and Cabrero, F.R. 2022. Metachromatic Leukodystrophy. StatPearls Publishing. Available at: https://www.ncbi.nlm.nih.gov/books/NBK560744/ [Accessed: 1 March 2023].

(3) Friedmann, T. and Roblin, R. 1972. Gene Therapy for Human Genetic Disease? Science 175(4025), pp. 949–955. doi: 10.1126/science.175.4025.949.

(4) Gene, Cell, & RNA Therapy Landscape: Q4 2022 Quarterly Data Report 2022. American Society of Cell and Gene Therapy. Available at: https://asgct.org/global/documents/asgct_citeline-q4-2022-report_final.aspx.

(5) Papanikolaou, E. and Bosio, A. 2021. The Promise and the Hope of Gene Therapy. Frontiers in Genome Editing 3. Available at: https://www.frontiersin.org/articles/10.3389/fgeed.2021.618346  [Accessed: 1 March 2023].

(6) Newborn blood spot screening: programme overview. 2018. Available at: https://www.gov.uk/guidance/newborn-blood-spot-screening-programme-overview [Accessed: 2 March 2023].

(7) Newborn Genomes Programme | Genomics England. Available at: https://www.genomicsengland.co.uk/initiatives/newborns [Accessed: 2 March 2023].