First in-patient treatment received for life-threatening immunodeficiency syndrome

Key points:

• A teenager has become the first patient in the UK and Europe to receive a targeted treatment for a rare, inherited immunodeficiency called Activated PI3-Kinase delta syndrome (APDS), which was responsible for the death of several of the patient’s relatives.
• As shared by Cambridge University Hospitals NHS Foundation Trust, Mary Catchpole, 19, was given a newly licensed drug called leniolisib (or Joenja) at Addenbrooke’s Hospital in Cambridge.
• The immunodeficiency syndrome, Activated PI3-Kinase delta syndrome (APDS), was discovered by researchers from several Cambridge-based research organisations and clinicians at Addenbrooke’s in 2013.
• Institute researchers contributed foundational knowledge about APDS, PI3-Kinase signalling and methodology central to the characterisation of APDS and the development of treatments.

As shared by Cambridge University Hospitals NHS Foundation Trust today, a teenager who lost family members including her mother because of a rare genetic hereditary illness, APDS, has become the first patient in the UK and Europe to have a new treatment approved for use on the NHS. This milestone follows the discovery of a rare, inherited immunodeficiency called Activated PI3-Kinase delta syndrome (APDS) by a team of Cambridge researchers in 2013.

APDS is a debilitating and life-threatening condition. People with APDS have a weakened immune system, making them vulnerable to repeated infections and autoimmune or inflammatory conditions, and at greater risk of developing blood cancers like lymphoma.

Mary Catchpole, 19, was given a newly licensed drug called leniolisib (or Joenja) at Addenbrooke’s Hospital in Cambridge. It is the first ever targeted treatment for APDS. Prior to this new treatment, the only treatments available to APDS patients include antibiotics for infections, immunoglobulin replacement therapy (to prevent infections and damage to organs) or a bone marrow or stem cell transplant.

The syndrome has significantly impacted Mary’s family on her mother’s side. Her aunt died aged 12, while her mother, uncle and grandmother all died in their 30s and 40s. Mary’s mother and uncle, who were Addenbrooke’s patients, played a key role in the discovery of ADPS in 2013.

They were offered DNA sequencing to see if there was a genetic cause for their immuno-deficiency. Cambridge researchers identified a change in their genes that increased activity of an enzyme called PI3-Kinase delta, resulting in the illness being named Activated PI3-Kinase delta syndrome (APDS). With APDS, the enzyme PI3-Kinase delta is ‘switched on’ all the time, preventing immune cells from fighting infection and leading to severe, recurrent respiratory infections.

The team behind the discovery included researchers from the University of Cambridge, Babraham Institute, MRC Laboratory for Molecular Biology, and clinicians from Addenbrooke’s¹. Institute researchers, possessing expertise in the PI3-Kinase signalling pathway, the role of PI3-Kinase delta in the immune system, and new methods to measure PI3-Kinase activity, provided insight and support to identify the genetic cause of the immunodeficiency, characterise its effect and test the effectiveness of inhibitors to reduce the activity of the overactive enzyme².

Dr Phill Hawkins, honorary group leader at the Babraham Institute and group leader from 1990 to 2025, recollects: “This is a great example of how an ecosystem of academic scientists, clinicians and pharma could collaborate quickly to help patients with APDS, both because we all knew each other and were in close geographical location.

“Alison Condliffe was a Clinical Fellow in our lab at Babraham for several years so was perfectly positioned due to her expertise in PI3-Kinase signalling to understand the implications of a mutation in PI3-Kinase delta.

‘’Jonathan Clark at the Institute had just developed a way to measure the product of PI3-Kinase activity in cells (a phospholipid called PIP3) which was key to confirming the driving effect of the mutation and also the efficiency of PI3-Kinase delta inhibitors to counteract the elevated levels seen in people with APDS.

“Add to that, Martin Turner’s and Klaus Okkenhaug’s research on the role of PI3-Kinase delta in the immune system and, in particular, Klaus’ work on the effects of enhanced PI3-Kinase delta activity in lymphocytes and you can see how the strength of complementary expertise existing at the Institute intersected so well with that at the University, the LMB and Addenbrooke’s. I’m delighted to hear today’s news that we can now treat APDS patients to proactively protect health rather than just manage the symptoms.”

The new treatment – with one tablet taken twice a day – works to inhibit the enzyme, effectively normalising cell signalling and restoring the function of the immune system.

Dr Anita Chandra, consultant immunologist at Addenbrooke’s hospital and Affiliated Assistant Professor at the University of Cambridge, who was a Clinical Fellow at the Institute from 2015 to 2019, said: “It is incredible to go from the discovery of a new disease in Cambridge to a treatment being approved and offered on the NHS, within the space of 12 years.

“This new drug will make a huge difference to people living with APDS, hopefully allowing patients to avoid antibiotics, immunoglobulin replacement and potentially even a stem cell transplant in the future.”

Mary said: “All my life I’ve had to have weekly infusions which make me feel like a pin cushion, and I’ve had to take lots of medication which has been tough.

“Now that I have this new treatment, it does feel bitter-sweet as my late mum and other affected members of my family never got the chance to have this new lease of life, but it is a gift. I feel blessed.”

Notes to Editors

This news article is adapted from the Cambridge University Hospitals NHS Foundation Trust press release: Patient with debilitating inherited condition receives new approved treatment on the NHS in Europe first

Publication references

1. Angulo et al. (2013) Phosphoinositide 3-kinase δ gene mutation predisposes to respiratory infection and airway damage. Science. doi: 10.1126/science.1243292.
2. Stark et al. (2018). PI3Kδ hyper-activation promotes development of B cells that exacerbate Streptococcus pneumoniae infection in an antibody-independent manner. Nature Communications. doi: 10.1038/s41467-018-05674-8

Press contact

For Cambridge University Hospitals NHS Foundation Trust (CUH): 

CUH Communications Department, Tel:  07920 862060, Email: cuh.press@nhs.net

At the Babraham Institute: Dr Louisa Wood, Head of Communications, louisa.wood@babraham.ac.uk

Image description

Left: the protein structure of PI3-Kinase delta as a heterodimer with P85 alpha, a regulatory subunit and a bound inhibitor. Protein features are highlighted, including the location of the amino acid changed in people with APDS (at position E1021K). The inhibitor (IC87114) is shown in red. Middle image: Mary and her father Jimmy Catchpole with Dr Anita Chandra at Addenbrooke’s Hospital. Right: Leniolisib (Joenja). Middle and right image: both by Mel Yeneralski Media Studio. Copyright Cambridge University Hospitals.

Affiliated researchers (contributing to the original 2013 publication, listed in alphabetical order):

Anita Chandra, a Wellcome Trust Postdoctoral Clinical Fellow at the Institute from 2015 to 2019, now consultant immunologist at Addenbrooke’s hospital and Affiliated Assistant Professor at the University of Cambridge

Jonathan Clark, Head of Biological Chemistry

Fabien Garçon, postdoctoral researcher with Klaus Okkenhaug at the time of the research and joint first author

Phill Hawkins, former group leader in the Institute’s Signalling research programme, current honorary group leader

Klaus Okkenhaug, BBSRC David Phillips Fellow and former group leader in the Institute’s Immunology research programme from 2003-2017

Len Stephens, former group leader in the Institute’s Signalling research programme, current honorary group leader

About the Babraham Institute

The Babraham Institute undertakes world-class life sciences research to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. Our research focuses on cellular signalling, gene regulation and the impact of epigenetic regulation at different stages of life. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and support healthier ageing. The Institute is strategically funded by the UKRI Biotechnology and Biological Sciences Research Council (BBSRC), through Institute Strategic Programme Grants and an Institute Core Capability Grant and also receives funding from other UK research councils, charitable foundations, the EU and medical charities.

About BBSRC

The Biotechnology and Biological Sciences Research Council (BBSRC) is part of UK Research and Innovation, a non-departmental public body funded by a grant-in-aid from the UK government.

BBSRC invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond.

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