UCLH BRC investigators have pioneered novel gene therapies that allow people with rare primary immunodeficiency disorders (PID) to lead long and healthy lives. The team has validated stem cell therapies as a safe treatment for adults with PID, enabling a new NHS policy ensuring they can access life-saving treatments.
In the UK approximately 5000 people are diagnosed each year with inherited immunodeficiencies, associated with mutations in up to 430 genes. Affected individuals have little or no functioning immune system and are at constant risk of life-threatening infection/autoimmunity/inflammatory diseases and cancer. In severe cases babies do not survive infancy without treatment.
Others with less severe immunodeficiency can remain undiagnosed into adulthood when life expectancy is shortened. As availability of genetic sequencing increases, more patients are being diagnosed.
UCL’s Centre for Immunodeficiency includes experts from UCL/UCLH/GOSH and RFH who are world-leaders in the development of novel gene and stem cell therapies for inherited immunodeficiencies. For children where compatible stem cell donors can be identified, stem cell transplants (HSCT) are routinely performed but this treatment has been unavailable to adults due to lack of evidence to support use.
During HSCT the patient’s own stem cells carrying genetic mutations are destroyed using chemotherapy and replaced with healthy donor cells. The risks of this chemotherapy are greater in older patients. UCLH developed a pioneering chemotherapy regimen that could be tolerated by adults. Using this, Professor Morris’ team at UCLH/RFH performed transplants in 29 adult
PID patients, achieving excellent 85% survival 3 years post-transplant(1).
This success paved the way for equal access to HSCT for PID patients regardless of their age, informing a commissioning policy by NHS England(2). UCLH has performed 68 transplants in adults, the largest number globally, allowing individuals to lead relatively normal lives without fear of life-threatening immunodeficiency complications.
These innovations have changed clinical practice internationally and adult patients are now considered for transplant worldwide. In 2018 Morris established an international multidisciplinary team which has discussed 98 of these ultra-rare patients to date. The team is also the first in the world to be using curative gene therapies to treat adults with PID for whom no compatible stem cell donor can be found(3).
1. Fox TA et al. Blood, 2018; 2. Allogeneic HSCT for PID (all ages); NHS England: 170129P, 2019; 3. Morris EC et al. Blood, 2018
