Last week it was announced that a new gene editing stem cell therapy for beta thalassemia would start to be made available on the NHS.

The therapy, called Casgevy, is developed by Vertex Pharmaceuticals and CRISPR Therapeutics and received approval from the UK regulator in November of last year. You can read about that announcement here.

It’s estimated that there are approximately 460 patients aged 12 or older with transfusion dependent beta thalassemia in England who are currently eligible for the treatment.

According to the NHS, the therapy will be offered across seven specialist centres and manufactured in the UK. [1]

What is beta thalassemia?

Beta thalassemia is an inherited blood disorder which affects the production of haemoglobin, a protein in red blood cells used to carry oxygen around the body.

Those affected by beta thalassemia produce little to no haemoglobin and as a result require frequent blood transfusions to supply red blood cells that can carry oxygen to tissues in the body.

Symptoms of beta thalassemia are associated with anaemia and range from mild – fatigue, weakness, headaches – to severe: heart palpitations, abdominal swelling, and jaundice.

Beta thalassemia has a debilitating impact on sufferers’ quality of life and it can also dramatically reduce life expectancy. [2]

What is Casgevy and how does it work?

The new therapy utilises a combination of the patient’s own stem cells and gene editing technology to reprogramme cells so that they produce healthy red blood cells.

Once the stem cells are harvested from the patient’s bone marrow they are then sent to a lab to undergo modification using the gene-editing tool CRISPR.

CRISPR effectively works like a pair of highly-targeted scissors, seeking out a specific section of DNA and editing a specific gene within it. In this instance, CRISPR targets the gene BCL11A.

During foetal development the body produces a unique form of haemoglobin in order to extract oxygen from the mother’s bloodstream. Once we’re born, BCL11A is responsible for silencing the production of foetal haemoglobin so that beta, or adult, haemoglobin can begin to be produced.

By targeting the BCL11A gene, the CRISPR tool is able to reverse the silencing process and re-encourage the production of foetal haemoglobin which, crucially, is left unaffected by beta thalassemia.

Once the stem cells have been edited to turn off BCL11A, they are then returned to patients via infusion and take residence in the bone marrow. The new, edited stem cells then begin to produce healthy red blood cells. [3]

In clinical trials, the new therapy removed the need for blood transfusions for at least a year in 39 of the 42 beta thalassemia sufferers treated. [4]

What’s next for the new therapy?

While the cost to the NHS of the new therapy is hefty – an estimated £1.6 million per patient – the treatment is being heralded as a cure, with the added benefit of eradicating the need for frequent blood transfusions, thereby reducing strain on healthcare services and improving patients’ quality of life outcomes.

With the new therapy expected to be rolled out in the coming weeks, attention now turns to whether the Casgevy treatment for sickle cell anaemia – another blood disorder affecting haemoglobin – will also be offered on the NHS, after its approval in November last year. [5]

What does this mean if I want to store my baby’s stem cells?

If it’s likely your baby could have beta thalassemia, it’s probably worth considering banking their umbilical cord blood.

Umbilical cord blood is rich in haematopoietic stem cells which are already being used in over 80 approved treatments, including for blood disorders.

Giving your baby the gift of stem cell storage may mean that they’ll one day be able to use their cord blood stem cells for the Casgevy therapy instead of the more intrusively procured bone marrow stem cells.

While not currently an approved version of the procedure, using the stem cells from banked umbilical cord blood rather than bone marrow could make for a less invasive procedure overall for your child, should they ever need it.

To find out more about how banking your baby’s stem cells could give them access to future medical advancements, request your free Welcome Pack below.

References

[1] (2024, August 8). Gene-editing therapy that could cure blood disorder thalassaemia for NHS patients. NHS England. https://www.england.nhs.uk/2024/08/gene-editing-therapy-that-could-cure-blood-disorder-thalassaemia-for-nhs-patients/#:~:text=The%20one%2Doff%20gene%20therapy,a%20severe%20form%20of%20thalassaemia.

[2] (2022, July 20). Beta Thalassemia. Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/23574-beta-thalassemia

[3] Gallagher, J. (2024, August 8). First gene-editing therapy may cure blood disorder. BBC News. https://www.bbc.co.uk/news/articles/c4gzldll44lo

[4] (2024, June 14). Vertex Presents Positive Long-Term Data On CASGEVY™ (exagamglogene autotemcel) at the 2024 Annual European Hematology Association (EHA) Congress. Vertex. https://news.vrtx.com/news-releases/news-release-details/vertex-presents-positive-long-term-data-casgevytm-exagamglogene

[5] (2024, August 8). World’s first gene editing therapy for blood disorder to be available to hundreds of patients in England. National Institute for Health and Care Excellence. https://www.nice.org.uk/news/articles/worlds-first-gene-editing-therapy-for-blood-disorder-to-be-available-to-hundreds-of-patients-in-england

Emerging research suggests that stem cell-based therapies could offer a new approach to treating influenza-related lung damage.

Mesenchymal stem cells (MSCs) in particular have been shown to repair lung tissue and modulate the immune response, providing hope for quicker and more complete recoveries from severe flu infections.

What is Influenza?

Influenza, otherwise commonly referred to as flu, is a viral infection that affects the respiratory system.

Symptoms can range from mild to severe, and in some cases, can lead to complications like pneumonia.

Among the most common symptoms are a high temperature, headache, loss of appetite, diarrhoea, and sickness. [1]

Current approaches to influenza, like vaccines and antiviral medications, remain preventative, focusing primarily on prevention and symptom management rather than virus-related damage.

With excess deaths from flu reaching approximately 14,500 in the UK alone last year – higher on average than the five years before the pandemic – severe influenza episodes continue to be a cause for concern. [2]

Who is Most Affected by Influenza?

Influenza can affect anyone, but certain demographics are at higher risk of severe illness and complications:

– Elderly individuals: People aged 65 and older are more susceptible to severe influenza due to a naturally weakened immune system and the higher chance of suffering from chronic health conditions.

– Young children: Infants and young children under the age of 5, especially those under 2 years old, are at a higher risk because their immune systems are still developing.

– Pregnant women: Pregnancy can alter the immune system, making expectant mothers more vulnerable to severe influenza and its complications.

– Individuals with chronic health conditions: People with conditions such as asthma, diabetes, heart disease, and weakened immune systems (e.g., due to cancer treatment or HIV) are at increased risk. [3]

How Can Stem Cells Help?

Stem cells, in particular MSCs, have shown promise in treating a variety of conditions due to their unique properties.

MSCs are found in various tissues, including umbilical cord blood, cord tissue, bone marrow, and fat or adipose tissue.

These cells have the ability to transform into different cell types and aid in tissue repair and regeneration.

They can also modulate immune responses and reduce inflammation, making them ideal candidates for treating diseases like influenza that cause significant damage to lung tissue. [4]

Repairing Lung Damage

MSCs can promote the regeneration of lung tissue by differentiating into various cell types needed for repair, including lung epithelial cells – the cells which contribute to the microbial immune response in the lungs. [5]

They can also reduce the number of inflammatory cells in the lungs, aiding in faster recovery in addition to releasing cytokines and growth factors that stimulate the proliferation of lung cells, helping restore lung function. [6]

Immune Modulation

One of the critical benefits of MSCs is their ability to modulate the immune response.

During an influenza infection, the immune system’s response can sometimes be overwhelming, leading to excessive inflammation and further lung damage.

MSCs help balance this response by reducing harmful inflammation and inhibiting the proliferation of T cells, which are often involved in excessive immune responses. This modulation contributes to a more controlled and effective immune response, preventing extra damage. [7]

Current Research

Recent studies and clinical trials have shown promising results using mesenchymal stem cells (MSCs) to treat lung damage caused by influenza.

Promising Animal Studies

In animal studies, MSC therapy has shown significant potential in treating lung injuries. For instance, in mouse models of a condition called pulmonary arterial hypertension (PAH), which causes high blood pressure in the lungs, MSCs were able to reduce lung damage. They achieved this by modulating the immune response and decreasing inflammation. [8]

Research suggests that human placenta mesenchymal stem cells (hPMSCs) also have the ability to regulate immune responses by inhibiting the proliferation of T-cells, thereby reducing inflammation deriving from excessive immune response.

Another study looked at lung injury caused by a toxic gas called phosgene. The researchers found that MSCs helped the lung’s own stem cells to proliferate and repair the damaged tissue. [9]

Increasing Human Trials

Interest in using MSCs to treat virus-induced lung injury is growing, and the number of clinical trials is on the rise. One notable trial from 2020 found that MSCs significantly reduced mortality in patients suffering from acute respiratory distress syndrome (ARDS) caused by the H7N9 subtype of influenza A. [10]

Another trial for ARDS sought to investigate whether MSCs derived from the placenta and umbilical cord could be used to treat severely ill COVID-19 patients. They were found to be effective in rapidly reducing respiratory distress and inflammation. [11]

These trials indicate that MSCs are safe to use and hold great potential for treating lung damage from influenza, though proving their effectiveness is still a work in progress.

The Future of MSC Therapy for Influenza

Stem cells, particularly MSCs, offer a promising new frontier in treating influenza-related lung damage.

As research progresses, we may soon see MSC-based therapies becoming a standard part of influenza treatment, providing hope for quicker and more complete recoveries from severe flu infections.

Saving the stem cells from your baby’s umbilical cord blood, cord tissue, and placenta is the perfect way to ensure they have access to future treatments for conditions like influenza.

To find out more about how cord blood banking could safeguard your baby’s health, download our free Welcome Pack by filling out the form below.

References

[1] (2023, August 9). Flu. NHS. https://www.nhs.uk/conditions/flu/

[2] UK Health Security Agency (2023, June 22). Excess deaths associated with flu highest in 5 years. Gov.uk. https://www.gov.uk/government/news/excess-deaths-associated-with-flu-highest-in-5-years

[3] U.S. Centers for Disease Control and Prevention (2024, March 22). Key Facts About Influenza (Flu). CDC. https://www.cdc.gov/flu/about/keyfacts.htm

[4] Jiang, W., & Xu, J. (2020). Immune modulation by mesenchymal stem cells. Cell proliferation, 53(1), e12712. https://doi.org/10.1111/cpr.12712

[5] Mendez, J. J., Ghaedi, M., Steinbacher, D., & Niklason, L. E. (2014). Epithelial cell differentiation of human mesenchymal stromal cells in decellularized lung scaffolds. Tissue engineering. Part A, 20(11-12), 1735–1746. https://doi.org/10.1089/ten.TEA.2013.0647

[6] Neelabh Datta. (2024) Stem Cell Therapy for SARS-CoV-2 and Influenza Virus Infections. BIOI. Vol. 5(1). DOI: 10.15212/bioi-2024-0016

[7] Weiss Andreas Robert Rudolf , Dahlke Marc Hendrik. (2019) Immunomodulation by Mesenchymal Stem Cells (MSCs): Mechanisms of Action of Living, Apoptotic, and Dead MSCs. Frontiers in Immunology. Vol.10. https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.01191

[8] Du Jun, et al. (2011) The Pathology of Bleomycin-Induced Fibrosis Is Associated with Loss of Resident Lung Mesenchymal Stem Cells That Regulate Effector T-cell Proliferation, Stem Cells, Volume 29, Issue 4, April 2011, Pages 725–735, https://doi.org/10.1002/stem.604

[9] Leeman, K.T., Pessina, P., Lee, JH. et al. (2019) Mesenchymal Stem Cells Increase Alveolar Differentiation in Lung Progenitor Organoid Cultures. Sci Rep 9, 6479. https://doi.org/10.1038/s41598-019-42819-1

[10] Chen, J., Hu, C., Chen, L., Tang, L., Zhu, Y., Xu, X., Chen, L., Gao, H., Lu, X., Yu, L., Dai, X., Xiang, C., & Li, L. (2020). Clinical Study of Mesenchymal Stem Cell Treatment for Acute Respiratory Distress Syndrome Induced by Epidemic Influenza A (H7N9) Infection: A Hint for COVID-19 Treatment. Engineering (Beijing, China), 6(10), 1153–1161. https://doi.org/10.1016/j.eng.2020.02.006

[11] Hashemian, S. R., Aliannejad, R., Zarrabi, M., Soleimani, M., Vosough, M., Hosseini, S. E., Hossieni, H., Keshel, S. H., Naderpour, Z., Hajizadeh-Saffar, E., Shajareh, E., Jamaati, H., Soufi-Zomorrod, M., Khavandgar, N., Alemi, H., Karimi, A., Pak, N., Rouzbahani, N. H., Nouri, M., Sorouri, M., … Baharvand, H. (2021). Mesenchymal stem cells derived from perinatal tissues for treatment of critically ill COVID-19-induced ARDS patients: a case series. Stem cell research & therapy, 12(1), 91. https://doi.org/10.1186/s13287-021-02165-4

The results from a Phase I/II clinical trial suggests a new stem cell-based therapy has the power to treat osteoarthritis (OA).

The trial, which was conducted by Australian biotechnology company Magellan Stem Cells, demonstrated that their ‘off-the-shelf’ stem cell therapy MAG200 significantly improved joint function and reduced pain for sufferers, with sustained benefits observed over longer periods.

It’s hoped that the new therapy will revolutionise OA treatment, helping to improve quality of life outcomes for millions of OA sufferers around the world. [1]

What is osteoarthritis?

Osteoarthritis is a condition that causes joints to become stiff and painful.

Normally, the everyday wear and tear that joints undergo is repaired by the body itself. For those who suffer from osteoarthritis, however, the protective cartilage on the ends of bones breaks down over time, causing pain, stiffness, and swelling.

Osteoarthritis most commonly affects the small joints in the hands, hips, knees, and neck. [2]

An estimated 10 million people in the UK alone have osteoarthritis, with the majority suffering from knee OA. [3]

A leading cause of disability, knee OA is associated with significant economic and healthcare burdens, often leading to total knee replacement surgery. A study by NICE in 2020 found that 100,000 knee replacements were carried out every year, with 89% of these being total knee replacements. [4]

It’s hoped that the new MAG200 stem cell therapy will not only improve outcomes for knee OA sufferers, but also alleviate some of the resource strain caused by currently limited treatment options.

What is the new MAG200 stem cell therapy and how does it work? 

The MAG200 therapy involves the localised injection of mesenchymal stem cells (MSCs) derived from adipose tissue into the area of the knee.

MSCs have emerged in recent times as a promising approach to addressing the unmet clinical needs of OA, namely pain caused by inflammation and the absence of protective cartilage tissue.

Previous research has shown that MSCs not only have the ability to reduce proinflammatory cytokines, thereby suppressing the pain associated with knee OA, but also to secrete transforming growth factor (TGFβ1) which helps with local tissue repair. [5]

These abilities make mesenchymal stem cells ideal for application in the treatment of knee OA and, therefore, in the MAG200 therapy.

What were the findings of the trial?

40 patients participated in the double-blind randomised control trial, all of whom had a documented diagnosis of moderate knee OA.

A double blind trial is one in which neither the researchers, nor the participants, know who has been administered what until after the trial has finished. This is done to reduce the chance of biases.

The participants were split into four cohorts of 10, wherein 8 were given MAG200, and 2 were given a placebo.

Following the application of MAG200, participants who had experienced a clinically meaningful improvement in either the pain or functionality associated with their OA were invited to respond using a variety of rating scales at months 1,3,6,9, and 12. [6]

A subsequent statistical analysis of responses, in addition to analysis of MRI data to measure improvements in tissue repair, demonstrated substantial benefits of MAG200, including:

• Sustained pain improvement of 58% at 12 months of follow-up.

• Doubling of quality of life scores for patients who received the stem cell treatment.

• Potential to halt the progression of osteoarthritis, with improvements in cartilage volume observed in treated patients.

Long-term follow-up demonstrated that the improvements from a single injection of donor stem cells were maintained beyond four years, highlighting the therapy’s durability and efficacy. [7]

What are the next steps for the MAG200 therapy?

According to a press release, Magellan Stem Cells hopes that future research will show the reproducibility of their results and validate their findings, paving the way for the rollout of MAG200 in Australia, beyond clinical trials.

Considered an ‘off-the-shelf’ therapy, it’s hoped that MAG200 will also have a considerable impact in the treatment of knee and other forms of OA, alleviating significant socioeconomic burdens associated with current OA treatments in the process. [8]

What does this mean for cord blood banking?

Although the mesenchymal stem cells used for the MAG200 therapy were derived from adipose donor tissue, mesenchymal stem cells are also found in umbilical cord blood and cord tissue, and could theoretically be used in autologous OA treatments (treatments using a patient’s own stem cells).

In fact, a 2021 study published in Nature’s open-access Scientific Reports Journal showed that an implantation of umbilical cord blood derived mesenchymal stem cells was more effective in treating knee OA than a high tibial osteotomy, a surgical procedure to realign the knee. [9]

Another study from 2023 found that mesenchymal stem cells from umbilical cord blood could enhance cartilage regeneration and reduce inflammation for sufferers of OA and were stipulated as being better equipped to both proliferate and differentiate than other sources of stem cells. [10]

While the MAG200 therapy is an allogeneic therapy, using donor stem cells, there is research to suggest that autologous mesenchymal stem cell treatments for OA using a patient’s own stem cells display clinically significant improvements across numerous parameters. [11]

This is good news if you’re considering saving your baby’s stem cells as it means that access to future treatments for conditions like OA could depend on whether a patient has their own stem cells available for use or not.

Saving your baby’s own stem cells also eliminates the risk of rejection in treatment, as your baby will always be a perfect match for their own stem cells.

To find out more about how cord blood banking could safeguard the health of your baby, sign up using the form below for a free Welcome Pack.

References

[1] Julien Freitag, et al., Safety and efficacy of an allogeneic adipose-derived mesenchymal stem cell preparation in the treatment of knee osteoarthritis: A Phase I/IIa randomised controlled trial, Osteoarthritis and Cartilage Open, Volume 6, Issue 3, 2024, 100500, ISSN 2665-9131, https://doi.org/10.1016/j.ocarto.2024.100500. (https://www.sciencedirect.com/science/article/pii/S2665913124000670)

[2] (2023, March 20). Overview: Osteoarthritis. NHS. https://www.nhs.uk/conditions/osteoarthritis/

[3] (2024). The State of Musculoskeletal Health. Versus Arthritis. https://versusarthritis.org/about-arthritis/data-and-statistics/the-state-of-musculoskeletal-health/#:~:text=10%20million%20people%20in%20the%20UK%20have%20Osteoarthritis%20(OA)%2C,estimated%20to%20have%20Psoriatic%20Arthritis.

[4] (2020). Resource impact report: Joint replacement (primary): Hip, knee and shoulder (NG157). NICE (National Institute for Healthcare and Excellence). https://www.nice.org.uk/guidance/ng157/resources/resource-impact-report-pdf-8708810221#:~:text=2%20Currently%20over%20100%2C000%20knee,1%25%20were%20patellofemoral%20knee%20replacements.

[5] Freitag, J., Bates, D., Boyd, R. et al. Mesenchymal stem cell therapy in the treatment of osteoarthritis: reparative pathways, safety and efficacy – a review. BMC Musculoskelet Disord 17, 230 (2016). https://doi.org/10.1186/s12891-016-1085-9

[6] Julien Freitag, et al., Safety and efficacy of an allogeneic adipose-derived mesenchymal stem cell preparation in the treatment of knee osteoarthritis: A Phase I/IIa randomised controlled trial, Osteoarthritis and Cartilage Open, Volume 6, Issue 3, 2024, 100500, ISSN 2665-9131, https://doi.org/10.1016/j.ocarto.2024.100500. (https://www.sciencedirect.com/science/article/pii/S2665913124000670)

[7] (2024, July 28). Australian researchers develop a donor stem cell therapy for the successful treatment of osteoarthritis – Magellan Stem Cells. Medianet. https://journalists.medianet.com.au/Release/1008949/8103088

[8] (2024, July 28). Australian researchers develop a donor stem cell therapy for the successful treatment of osteoarthritis – Magellan Stem Cells. Medianet. https://journalists.medianet.com.au/Release/1008949/8103088

[9] Jung, SH., Nam, BJ., Choi, CH. et al. Allogeneic umbilical cord blood-derived mesenchymal stem cell implantation versus microdrilling combined with high tibial osteotomy for cartilage regeneration. Sci Rep 14, 3333 (2024). https://doi.org/10.1038/s41598-024-53598-9

[10] Zhang, Pengwei et al. “Human umbilical cord mesenchymal stem cells promoting knee joint chondrogenesis for the treatment of knee osteoarthritis: a systematic review.” Journal of orthopaedic surgery and research vol. 18,1 639. 29 Aug. 2023, doi:10.1186/s13018-023-04131-7

[11] Prodromos, Chadwick et al. “Autologous Mesenchymal Stem Cell Treatment is Consistently Effective for the Treatment of Knee Osteoarthritis: The Results of a Systematic Review of Treatment and Comparison to a Placebo Group.” Medicines (Basel, Switzerland) vol. 7,8 42. 24 Jul. 2020, doi:10.3390/medicines7080042