Research achievements: Tackling the underlying cause of cystic fibrosis
Research studies tackling the underlying cause of cystic fibrosis (CF) have ranged from helping the CF protein to work again to looking at alternative proteins that can compensate for a lack of working CF protein. On a genetic level, researchers are investigating ways to alter the CF gene, to allow a fully functioning CF protein to be produced. Here we explain how our research funding has made a difference in this area.
Read more about research currently underway to investigate the underlying cause of CF.
Best treatment for you
There are over 2,000 different mutations of the CF gene that can cause cystic fibrosis. Some of these mutations are very common (over 90% of people with CF in the UK have at least one copy the ‘F508del’ mutation) and some of them are very rare, affecting one or two families in the UK with cystic fibrosis. We funded research in Dr Paola Vergani’s lab at UCL to develop drug screening methods for drugs that might be effective for the rarer CF mutations. Dr Vergani’s method uses light-emitting markers that show whether a would-be drug can help rescue the CF protein. Using this new method will allow speedier and more effective drug development for new CFTR modulators in the future.
Dr Mike Gray at the University of Newcastle is pursuing an alternative approaching to developing effective treatments for CF by looking to enhance the activity of proteins that work in a similar way. Conducted within a Trust-funded Strategic Research Centre (SRC) programme, Dr Gray and his international and multi-disciplinary expert team have identified a number of proteins that could be changed make the lung environment healthier for people with cystic fibrosis. They’ve been awarded a new SRC grant to look for drugs that can alter these proteins, using lab methods developed in the first SRC. If this long-term goal is successful these drugs would be suitable for anyone with CF, irrespective of their genotype.
Methods of treating CF on a genetic level include gene therapy and gene editing. Good progress is being made towards genetic-based treatments. While these are unlikely to be available as standard to people with CF for many years, when they become available, they could make a significant difference to everyone.
Gene therapy and the UK Gene Therapy Consortium
The UK Gene Therapy Consortium (GTC) is a group of researchers based at Imperial College London, the University of Oxford and the University of Edinburgh who are working together to develop gene therapies for cystic fibrosis. It was set up with support from the Trust in 2001. The GTC has been developing two approaches to gene therapy, a Wave 1 product using liposomes (a kind of fat) to deliver the healthy copy of the gene into the lungs, and a Wave 2 product using a viral vector as the delivery mechanism. The Wave 1 product was successful in stabilising lung disease in CF in a clinical trial. It proved the concept that gene therapy can have a beneficial effect on lung disease, and paved the way for the Wave 2 product. From 2017 onwards the GTC has been concentrating on the Wave 2 product predominately, building on the foundations of knowledge gained from the development of the Wave 1 product.
Following funding from the Trust to ensure work investigating both products could continue, in 2018 a new three-way partnership was announced where the GTC joined forces with pharma company Boehringer Ingelheim on research and development, and Oxford Biomedica on the viral delivery manufacturing for the Wave 2 gene therapy product. This collaboration will provide the substantial level of investment needed to take the Wave 2 product towards clinical trials, to establish its safety and effectiveness in humans.
The Trust has invested over £1 million in the GTC over the last five years, ensuring its work in both products could continue while searching for a major partner with the resources to take one of the products forwards.
A research advance published in 2012 meant that gene editing therapies may be feasible in the future. While a huge amount of research has been conducted into gene editing since then, it remains an extremely new technology. The Trust is proud to have supported early research studies into the details of how this technique may work best as a future therapy for cystic fibrosis, and this work is currently ongoing .
Repairing lung cells
The effects of the malfunctioning CF protein and cycles of chronic infections can lead to permanent damage to the lungs. Currently it isn’t possible to repair lung damage that occurs in people with CF and as the lungs become more damaged a lung transplant may be required. Researchers are at the early stages of investigating an alternative to a lung transplant. Investigations of whether it is possible to replace the cells within the lungs, without needing to replace the whole organ are underway. We funded very preliminary studies to test the use of both stem cell and gene editing technologies to create cells suitable for this ‘lung graft’ approach. This area of research is now continuing within our UK Cystic Fibrosis Innovation Hub at the University of Cambridge.
Research we fund
We fund research to tackle some of the most pressing issues in CF today. Find out how your donations are making a difference.
What is CF?
Cystic fibrosis, or CF, affects the lungs, digestive system and other organs. There are around 11,000 people living with it in the UK.
Get in touch with us to speak to someone on our Helpline, find out about an event or speak to our press team.
Utafiti wa msingi wa cystic fibrosis (CF) unajumuisha utafiti wa msingi wa sababu ya cystic fibrosis (CF) na utafiti wa msingi wa sababu ya cystic fibrosis (CF) na utafiti wa msingi wa sababu ya cystic fibrosis (CF). Katika hatua ya kibinadamu, watafiti wanachunguza njia za kubadilisha jeni la CF, ili kuruhusu protini ya CF inayofanya kazi kikamilifu kutengenezwa. Hapa tunaelezea jinsi ufadhili wetu wa utafiti umefanya tofauti katika eneo hili. Soma zaidi kuhusu utafiti unaofanywa sasa ili kuchunguza kisababishi cha CF. Kuna zaidi ya 2,000 tofauti mutations ya CF jeni ambayo inaweza kusababisha cystic fibrosis. Baadhi ya mabadiliko haya ni ya kawaida sana (zaidi ya 90% ya watu walio na CF nchini Uingereza wana angalau nakala moja ya mabadiliko ya F508DEL) na baadhi yao ni nadra sana, kuathiri familia moja au mbili nchini Uingereza na cystic fibrosis. Utafiti wa utafiti wa Dr. Paola Vergani ulifanyika katika UCL, Uingereza, na ulifanyika kwa lengo la kugundua dawa za kulevya ambazo zinaweza kuwa na athari kwa mabadiliko ya CF. Mbinu ya Dakt. Vergani hutumia alama zinazotoa nuru ambazo huonyesha kama dawa inayoweza kusaidia kuokoa protini ya CF. Kwa kutumia mbinu hii mpya itaruhusu maendeleo ya dawa ya haraka na yenye ufanisi zaidi kwa modulators mpya za CFTR katika siku zijazo. Mike Gray, Mtaalamu wa Ugonjwa wa Ugonjwa wa Kifua, anafanya utafiti wa kuimarisha utendaji wa protini zinazofanya kazi kwa njia hiyo. Katika utafiti uliofanywa na utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti. Wamepokea ruzuku mpya ya SRC kutafuta dawa zinazoweza kubadilisha protini hizi, kwa kutumia mbinu za maabara zilizotengenezwa katika SRC ya kwanza. Ikiwa lengo hili la muda mrefu linafanikiwa, dawa hizi zitakuwa sahihi kwa mtu yeyote aliye na CF, bila kujali genotype yao. Mbinu za kutibu CF katika kiwango cha urithi zinatia ndani tiba ya jeni na uhariri wa jeni. Maendeleo mazuri yanafanywa kuelekea matibabu ya chembe za urithi. Ingawa hizi hazitakuwa na uwezo wa kuwa na watu wenye CF kwa miaka mingi, zinapopatikana, zinaweza kufanya tofauti kubwa kwa kila mtu. UK Gene Therapy Consortium (UKGT) ni kikundi cha watafiti kutoka Chuo Kikuu cha Imperial London, Chuo Kikuu cha Oxford na Chuo Kikuu cha Edinburgh ambao wanafanya kazi pamoja kuendeleza tiba za jeni kwa cystic fibrosis. Ilianzishwa na msaada wa Trust mnamo 2001. GTC imekuwa ikiendeleza mbinu mbili za tiba ya jeni, bidhaa ya Wimbi 1 inayotumia liposomes (aina ya mafuta) kutoa nakala ya afya ya jeni kwenye mapafu, na bidhaa ya Wimbi 2 inayotumia vector ya virusi kama utaratibu wa utoaji. Kwa mfano, dawa ya Wave 1 ilifanikiwa katika kudumisha hali ya mapafu ya CF katika majaribio ya kliniki. Utafiti huo ulithibitisha kuwa tiba ya jeni inaweza kuwa na athari nzuri kwa magonjwa ya mapafu na kuandaa njia ya kuunda bidhaa ya Wave 2. Tangu mwaka 2017, GTC imekuwa ikizingatia bidhaa ya Wimbi la 2, ikijenga juu ya misingi ya maarifa yaliyopatikana kutoka kwa maendeleo ya bidhaa ya Wimbi la 1. Baada ya fedha kutoka kwa Trust kuhakikisha kazi ya kuchunguza bidhaa zote mbili inaweza kuendelea, ushirikiano mpya wa njia tatu ulitangazwa mnamo 2018 ambapo GTC ilijiunga na kampuni ya dawa ya Boehringer Ingelheim katika utafiti na maendeleo, na Oxford Biomedica katika utengenezaji wa utoaji wa virusi kwa bidhaa ya tiba ya jeni ya Wimbi la 2. Ushirikiano huu utatoa kiwango kikubwa cha uwekezaji kinachohitajika kuchukua bidhaa ya Wave 2 kuelekea majaribio ya kliniki, ili kuanzisha usalama na ufanisi wake kwa wanadamu. Trust imewekeza zaidi ya £ 1 milioni katika GTC katika miaka mitano iliyopita, kuhakikisha kazi yake katika bidhaa zote mbili inaweza kuendelea wakati kutafuta mpenzi mkubwa na rasilimali kuchukua moja ya bidhaa mbele. Utafiti uliochapishwa mwaka 2012 ulionyesha kwamba matibabu ya kuhariri jeni yanaweza kufanywa katika siku zijazo. Ingawa utafiti mwingi umefanywa kuhusu kurekebisha chembe za urithi tangu wakati huo, bado ni teknolojia mpya sana. Trust inajivunia kuunga mkono utafiti wa mapema juu ya jinsi mbinu hii inaweza kufanya kazi bora kama tiba ya baadaye ya cystic fibrosis, na kazi hii inaendelea sasa. Uharibifu wa seli za mapafu: Madhara ya proteini ya CF na mzunguko wa maambukizo ya muda mrefu yanaweza kusababisha uharibifu wa kudumu kwa mapafu. Kwa sasa haiwezekani kurekebisha uharibifu wa mapafu unaotokea kwa watu wenye CF na kama mapafu yanazidi kuharibiwa upandikizaji wa mapafu unaweza kuhitajika. Watafiti wako katika hatua za mapema za kuchunguza mbadala wa upandikizaji wa mapafu. Uchunguzi wa ikiwa inawezekana kubadilisha chembe ndani ya mapafu, bila kuhitaji kubadilisha kiungo chote unaendelea. Tulifadhili masomo ya awali sana kupima matumizi ya teknolojia ya chembe za msingi na uhariri wa jeni ili kuunda seli zinazofaa kwa mbinu hii ya "kuchanganya mapafu". Utafiti huu unaendelea katika Kituo chetu cha Ubunifu cha UK Cystic Fibrosis katika Chuo Kikuu cha Cambridge. Utafiti wa fedha za fedha za fedha za fedha za fedha za fedha za fedha za fedha za fedha za fedha za fedha za fedha za fedha za fedha za fedha za fedha za fedha za fedha za fedha za fedha za fedha za fedha za fedha za fedha za fedha za fedha za fedha za fedha za fedha. Jifunze jinsi michango yako inavyofanya tofauti. CF ni nini? Cystic fibrosis (CF) huathiri mapafu, mfumo wa kumeng'enya chakula, na viungo vingine vya mwili. Watu 11,000 wanaishi na ugonjwa huo nchini Uingereza. Wasiliana nasi kwa kuzungumza na mtu kwenye Helpline yetu, kujua kuhusu tukio au kuzungumza na timu yetu ya waandishi wa habari.