BBC article about successful immune system med for rare genetic ADPS disorder

[Kiristar]

New drug offers potential cure for ultra rare inherited condition

A teenage patient who helped discover a rare condition is the first to benefit from a new treatment.

www.bbc.co.uk

 

[RedFox]

This is very good. it's a drug targeted at the condition's pathology and not gene therapy.

 

[Kiristar]

This is very good. it's a drug targeted at the condition's pathology and not gene therapy.

My mistake sorry I've edited the title to correct this.

 

[Utsikt]

Leniolisib has a list price of £352,000 a year, but was approved as cost effective by the health regulator NICE after the NHS negotiated a substantial, confidential discount.

For reference: Daratumumab is a lot cheaper, and will probably become even cheaper when the patents runs out.

It is interesting to see how testing for APSD is quite strongly recommended, even before this treatment was available.

For Huntington’s disease (HD), which is inherited the same way, progressive, and eventually fatal, there is much more focus on everyone doing what’s right for them. I’m assuming the scales shift when you’ve got at least some treatment options like for APSD, and knowing if you’re positive might actually make a difference by getting access to treatments. The main concern for HD is if you want to test before you get children, and what a positive test might mean for children you’ve already got.

 

[Hutan]

Prof Sergey Nejentsev from the University of Cambridge who led the research that discovered APDS said: "As soon as we understood the cause of APDS, we immediately realised that certain drugs could be used to inhibit the enzyme that is activated in these patients.

Leniolisib does precisely that. I am delighted that we finally have a treatment which will change the lives of APDS patients."

Leniolisib has a list price of £352,000 a year, but was approved as cost effective by the health regulator NICE after the NHS negotiated a substantial, confidential discount.

NICE estimates the drug could benefit up to 50 patients over the age of 12 in England.

 

[SNT Gatchaman]

Modulating the PI3K Signalling Pathway in Activated PI3K Delta Syndrome: a Clinical Perspective (2023)
Berglund, Lucinda J.

Activated phosphoinositide-3-kinase (PI3K) δ syndrome (APDS) is an inborn error of immunity characterised by immune dysregulation. Since the discovery of genetic mutations resulting in PI3Kδ overactivation, treatment of APDS patients has begun to focus on modulation of the PI3K pathway in addition to supportive therapies. The mTOR inhibitor sirolimus has been used effectively for some clinical manifestations of this condition, however the arrival of specific PI3Kδ inhibitor leniolisib has shown promising early results and may provide a more targeted approach.

This review summarizes key aspects of PI3K pathway biology and discusses potential options for nuanced modulation of the PI3K pathway in APDS from a clinical perspective, highlighting differences from PI3K inhibition in haematological malignancies.

Link | PDF | Journal of Clinical Immunology [Open Access]

 

[Hutan]

https://www.s4me.info/threads/ident...pective-cohort-study-2025-sayyab-et-al.44271/

From a recent post-Covid-19 condition study:

Pathway analysis revealed enrichment in PI3K-Akt and AMPK signaling pathways, potentially underlying the observed efficacy of metformin in reducing PCC incidence.

The PI3K/AKT/mTOR pathway is an intracellular signaling pathway important in regulating the cell cycle. Therefore, it is directly related to cellular quiescence, proliferation, cancer, and longevity. PI3K activation phosphorylates and activates AKT, localizing it in the plasma membrane. AKT can have a number of downstream effects such as activating CREB, inhibiting p27, localizing FOXO in the cytoplasm, activating PtdIns-3ps, and activating mTOR which can affect transcription of p70 or 4EBP1. There are many known factors that enhance the PI3K/AKT pathway including EGF, shh, IGF-1, insulin, and calmodulin. Both leptin and insulin recruit PI3K signalling for metabolic regulation. The pathway is antagonized by various factors including PTEN, GSK3B, and HB9.

In many cancers, this pathway is overactive, thus reducing apoptosis and allowing proliferation. This pathway is necessary, however, to promote growth and proliferation over differentiation of adult stem cells, neural stem cells specifically. It is the difficulty in finding an appropriate amount of proliferation versus differentiation that researchers are trying to determine in order to utilize this balance in the development of various therapies. Additionally, this pathway has been found to be a necessary component in neural long term potentiation.