Developing a safe prenatal test for recessive diseases including cystic fibrosis
Professor Lyn Chitty, Great Ormond Street Hospital and Institute of Child Health, London, UK
Our contribution: £49,000
Partners: Action Medical Research and Great Ormond Street Hospital, £150,000
It is possible to test if a baby has cystic fibrosis during pregnancy. Currently, the test involves taking a few cells from the amnioitic fluid that surrounds a growing fetus, usually by inserting a needle through the mother’s abdomen to the womb (uterus). This can be performed between 11 and 14 weeks of the pregnancy. However, this test is associated with a risk of miscarrying the baby.
Professor Chitty and colleagues are working on a test that can be performed using a blood sample from the mother from 9 weeks of pregnancy. The test can analyse the cystic fibrosis gene (CFTR) in the baby’s DNA, from fragments of it that enter into the mother’s blood stream. This type of test is known as a ‘cell-free fetal DNA’ (cffDNA) test or a ‘non-invasive prenatal’ test(NIPT).
At the same time as a developing a test for CF, Professor Chitty is also developing a test for the genetic neuromuscular disease spinal muscular atrophy (SMA).
You can read a more detailed description of the research on the Action Medical Research website.
Using stem cells and gene editing to repair damaged lung cells
Professor Ludovic Vallier, MRC Cambridge Stem Cell Institute, University of Cambridge, UK
Our contribution: £100,000
Partner: Cystic Fibrosis Foundation, £500,000
Researchers are investigating whether a combination of stem cell technology and gene editing may provide an alternative to lung transplant. This works by replacing damaged CF-affected lung cells with new, healthy and unaffected lung cells. The aim is to create stem cells from other cells within the body of the person with cystic fibrosis (using a method called ‘induced pluripotent stem cells’). In the lab, they will then use gene editing to correct the mutation in the gene that causes CF called the ‘CFTR’ gene. The next stage will then be to convert the stem cells into lung cells and finally to work out a way of getting the new lung cells delivered and working to the lining of the lungs.
Developing a drugs screen for people with rare cystic fibrosis mutations
Dr Paola Vergani, UCL, London, UK
Our contribution: £75,000
Partner: Sparks, £75,000
There are over 2.000 different mutations of the CFTR gene that can cause cystic fibrosis. Some of these mutations are very common (over 90% of people with CF have the ‘F508del’ mutation). Addressing these common mutations is the focus of most drug development. The aim of this project is to develop drug screening methods for drugs that might be effective for the rarer CFTR mutations.
To tell whether a drug is working Dr Vergani is developing some fluorescent labels that attach themselves to the damaged (mutated) section of the CFTR gene. When the drugs are added to the cells, she’ll be able to track any changes in the function of the CFTR gene using the fluorescent tags.
Developing a gene editing method that will work for any CFTR gene mutation
Dr Patrick Harrison, University College Cork, Ireland
Our contribution: £42,000
Partner: Cystic Fibrosis Foundation, £126,000
One way to treat cystic fibrosis is to permanently correct the damaged CFTR gene that causes the condition, known as gene editing. This technique is still under development and it is not yet available to people with CF. Most gene editing methods currently in development work by correcting specific mistakes within the gene, for example, correcting the common F508del mutation. However, Dr Harrison is developing a method of gene editing that has the potential to correct any gene mutation.
You can read more about Dr Harrison’s research in an article on our website.
Testing a new form of gene therapy
Professor Stephen Hart, UCL
Our contribution: £51,721
Partner: Action Medical Research, £103,442
One way to treat cystic fibrosis is to deliver new, healthy copies of CFTR, the gene that is damaged in cystic fibrosis, a process known as gene therapy. An important and difficult part of developing a gene therapy is to work out the logistics: from the safe delivery of the new gene, to the point where healthy copies of the CFTR protein are produced.
In this research project Professor Hart will develop a gene therapy approach that cuts out some of the more difficult steps of this process. This new method might make it easier and quicker to get a gene therapy ready for use in the clinic. Rather than delivering new healthy copies of the CFTR gene itself, Professor Hart’s approach is to deliver the template the cells use to make the protein from the gene. This template is called mRNA. This research project will investigate the best way to ‘package’ the mRNA to deliver it safely into the lung cells.
You can read more about this research on Action Medical Research's website.