The Work in Progress
Details of the work being carried out at the
Royal London Hospital and Great Ormond Street Hospital
The Royal London Hospital
1. Development of computerised database for patients with CIP
2. Studies of quality of life in children on home parenteral nutrition
3. Studies of voltage gated potassium channels in gastrointestinal tract
1. Pseudo-obstruction Database
A database has been developed which contains details of CIP patients the care of the Royal London Hospital. The database has been designed to cover many aspects of pseudo-obstruction, drawing on the professional opinions of colleagues within Barts and the London NHS Trust and Queen Mary University of London.
Current developments include
Creating a form to allow the database to be updated by multiple users
Redesign to convert it from a monolithic to relational database
Modification to encompass Rome III criteria classification where appropriate
Quality of life data collection and input
2. Quality of life and Pseudo-obstruction
A study is underway to determine the quality of life of people suffering from pseudo-obstruction using validated questionnaires.
3. Studies on intestinal voltage-gated ion channels
Disorders of ion channel (channelopathies) include cystic fibrosis (chloride channel), various forms of epilepsy and ataxia (sodium and potassium channels), muscle disorders such as periodic paralysis and myotonia (sodium, chloride) and various renal disorders which resort in abnormal sodium and potassium handling.
Channels can also be affected by autoantibodies directed at the nicotinic acetyl choline receptors which affect ion channel function (myasthenia and slow channel syndrome). The question arises to what extent ion channels exist in the intestine and whether some of the diseases of motility which we see, both common and rare, are the result of abnormalities in them.
Dr Hubball’s first studies have shown voltage-gated potassium channels to be widely distributed throughout the mouse intestine, not only in the surface cells in the stomach, small intestine and colon, but also in the neural ganglia lying beneath the surface and in intestinal muscle. This raises possibilities that surface cell damage could result in an immune response, which damages other cells with the same channels, and also that some of the rarer dysmotility disorders might be due to genetic abnormalities of these channels, or the result of auto-antibodies produced to them.
1. Development of computerised database for patients with CIP
2. Studies of quality of life in children on home parenteral nutrition
3. Studies of voltage gated potassium channels in gastrointestinal tract
1. Pseudo-obstruction Database
A database has been developed which contains details of CIP patients the care of the Royal London Hospital. The database has been designed to cover many aspects of pseudo-obstruction, drawing on the professional opinions of colleagues within Barts and the London NHS Trust and Queen Mary University of London.
Current developments include
Creating a form to allow the database to be updated by multiple users
Redesign to convert it from a monolithic to relational database
Modification to encompass Rome III criteria classification where appropriate
Quality of life data collection and input
2. Quality of life and Pseudo-obstruction
A study is underway to determine the quality of life of people suffering from pseudo-obstruction using validated questionnaires.
3. Studies on intestinal voltage-gated ion channels
Disorders of ion channel (channelopathies) include cystic fibrosis (chloride channel), various forms of epilepsy and ataxia (sodium and potassium channels), muscle disorders such as periodic paralysis and myotonia (sodium, chloride) and various renal disorders which resort in abnormal sodium and potassium handling.
Channels can also be affected by autoantibodies directed at the nicotinic acetyl choline receptors which affect ion channel function (myasthenia and slow channel syndrome). The question arises to what extent ion channels exist in the intestine and whether some of the diseases of motility which we see, both common and rare, are the result of abnormalities in them.
Dr Hubball’s first studies have shown voltage-gated potassium channels to be widely distributed throughout the mouse intestine, not only in the surface cells in the stomach, small intestine and colon, but also in the neural ganglia lying beneath the surface and in intestinal muscle. This raises possibilities that surface cell damage could result in an immune response, which damages other cells with the same channels, and also that some of the rarer dysmotility disorders might be due to genetic abnormalities of these channels, or the result of auto-antibodies produced to them.
Great Ormond Street Hospital
1. Understanding causes of intestinal pseudo-obstruction
2. Developing stem cell therapies for gut neuromuscular disease
3. Inflammation and gut motility disorders
4. Artificial feeding and parenteral nutrition in children with gut motility disorders
1. Understanding causes of CIP
A major focus of the department is the study of the mechanisms involved in normal development of the gut nerves, muscle and intersitial cells of cajal, and how abnormal development may lead to disorders such as congenital pseudo-obstruction, Hisrchsprung’s disease and intractable constipation. To date work has shown that both quantitative and qualitative disorders occur in patients with CIPS, and the team addressing how such defects arise and how they may be rescued.
2. Developing stem cell therapies for gut neuromuscular disease
The research team has been one of the first to show that stem cells that give arise to ENS can be isolated from human gut even after birth. Collaborators are carrying out similar studies with muscle. Preliminary studies are investigating whether such cells can be transplanted into gut lacking ENS or muscle and correct the functional defect. Results to date have promising and although the studies are preliminary they suggest such therapies may be feasible to replace/replenish absent/abnormal components of gut nerves and muscle. This may be applicable to both childhood and adult intestinal pseudo-obstructive disorders.
3. Inflammation and Gut Motility Disorders
Inflammation is often an inherent component of both congenital and pseudo-obstruction and other gut motility orders. Working in collaboration with the surgical team and immunobiologists this research aims to understand the aetiology of this process and its treatment. Preliminary work suggests that genetic factors may underline this process and contribute to both the inflammation as well as the motility phenotype.
4. Artificial feeding and parenteral nutrition in children with gut motility disorders
Currently in the UK, Great Ormond Street Hospital has the largest cohort of children with CIPs on home parenteral nutrition. This has facilitated a number of ongoing studies on long-term outcomes and specific risk factors related to this nutrition including infection and thrombosis.
1. Understanding causes of intestinal pseudo-obstruction
2. Developing stem cell therapies for gut neuromuscular disease
3. Inflammation and gut motility disorders
4. Artificial feeding and parenteral nutrition in children with gut motility disorders
1. Understanding causes of CIP
A major focus of the department is the study of the mechanisms involved in normal development of the gut nerves, muscle and intersitial cells of cajal, and how abnormal development may lead to disorders such as congenital pseudo-obstruction, Hisrchsprung’s disease and intractable constipation. To date work has shown that both quantitative and qualitative disorders occur in patients with CIPS, and the team addressing how such defects arise and how they may be rescued.
2. Developing stem cell therapies for gut neuromuscular disease
The research team has been one of the first to show that stem cells that give arise to ENS can be isolated from human gut even after birth. Collaborators are carrying out similar studies with muscle. Preliminary studies are investigating whether such cells can be transplanted into gut lacking ENS or muscle and correct the functional defect. Results to date have promising and although the studies are preliminary they suggest such therapies may be feasible to replace/replenish absent/abnormal components of gut nerves and muscle. This may be applicable to both childhood and adult intestinal pseudo-obstructive disorders.
3. Inflammation and Gut Motility Disorders
Inflammation is often an inherent component of both congenital and pseudo-obstruction and other gut motility orders. Working in collaboration with the surgical team and immunobiologists this research aims to understand the aetiology of this process and its treatment. Preliminary work suggests that genetic factors may underline this process and contribute to both the inflammation as well as the motility phenotype.
4. Artificial feeding and parenteral nutrition in children with gut motility disorders
Currently in the UK, Great Ormond Street Hospital has the largest cohort of children with CIPs on home parenteral nutrition. This has facilitated a number of ongoing studies on long-term outcomes and specific risk factors related to this nutrition including infection and thrombosis.
