Bath Supraregional Tuberous Sclerosis Complex (TSC) Service for Adults and Children |
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Research
Research and Publications
We have an active and long-standing programme of research in Bath, which was originally founded by Professor John Osborne. This includes clinical trials of new treatments and population studies of patients with TSC.
Current team research:
- Side effects and efficacy of treatment in Tuberous Sclerosis
- Drug repurposing
- Artificial intelligence and machine learning
Preliminary findings from a TSC scientific conference in Toronto June 2019
Below are summary's of presentations from scientist from across the globe that might be of interest to patients and families. They have not been published in scientific journals as yet.
Adult women with more extensive and earlier onset skin involvement also showed more extensive lung involvement says Dr Thomas N. Darling from Bethesda, Maryland Epistop study – is a European study looking at early treatment of seizures in children with TSC. They have found that a high tuber numbers at 4 months of age was associated with learning problems and treatment resistant epilepsy at 2 years of age. Small groups of patients appear to benefit from using Vigabatrin before the onset of clinical seizures.
A group (Dr Peter E. Davis) from Boston Childrens Hospital looked at 166 children in their database and found that seizures occurred in 73% of patients by 1 year of age. Infantile spasm tend to occur at 3-9 months of age and focal seizures up to age 21 months. Some of these patients started showing increase EEG connectivity prior to onset of spasm, suggesting that it may be possible to have EEG clues to the onset of spasm before they occur. Larger head circumference in infancy appears to correlate with number of types of seizures - i.e. bigger head, more seizure types.
Epidiolex (Cannibidiol) in children with seizures and TSC appears to be effective as used in a trial of over 200 children in Boston. There were around 10% of patients in the treatment who had withdrawn from the study due to side effects. Most of the side effects were previously seen in other Cannibidiol studies e.g. diarrhoea, vomiting, abnormal liver enzyme and infections.
In a study of language predictors of Autism in TSC, a group from several TSC clinics in USA, found that by 12 months of age it was possible to predict children who were going to have a diagnosis of Autism later in childhood with a fair level of accuracy.
A clinic in Germany has found an interaction between the use of Everolimus and Cannibidiol. A child who was already on Everolimus and then had Cannibidiol added for seizure treatment. This child's Everolimus levels which was previously stable, started climbing up to toxic levels and had to have the Everolimus dose reduce significantly.
The Cincinnati Childrens Hospital looked at the MRIs of 193 patients and see if they could predict which patients subependymal nodules are likely to become SeGA's. It appears that the genetics, number of SEN, age of onset did not predict SEGA growth.
Skin side effects of mTOR inhibitors. A group from Maryland, USA looked at 29 patients who were treated with Sirolimus or Everolimus. 28 of these patients developed skin or hair changes during the treatment period. These changes consisted of acne (55%), hand or feed swelling, (31%), poor wound healing (28%), Cellulitis (3%).
Prof Patrick Bolton from London has a long term follow up study of 125 TSC patients and found that TSC1 or 2 did not predict autism or ADHD prevalence. Autism was predicted by the number of tubers and seizure severity in early life. ADHD was associated with IQ and ASD.
A group from USA looked at families with TSC and found several genes that modify the severity of TSC within different members of the same family. Further work will be required to see if this is a consistent finding.
Prof David Kwaitkowski in Boston has a study on patients who are mosaic (not all cells carry the genetic change) for TSC. 8% were TSC 1 and the rest TSC2. Patients who are mosaic tend to have more facial angiofibroma, and renal AMl but less epilepsy and autism. Different tissues in their body tend to have slightly different genetic changes - e.g. skin vs blood or semen. They have suggested that those with no genetic diagnosis in their blood sample could have their diagnosis made on their tissue biopsy.