Clinical Studies in HTLV infection at NCHR
The first trial explored the potential that therapies that work against HIV enzymes and are known to have activity against HTLV-1 enzymes when tested in the lab, would reduce the amount of HTLV-1 in the blood of patients with HAM. Unfortunately this was not the case (9) and our attention moved to exploring the role of treatments that suppress inflammation.
The first anti-inflammatory drug that we investigated was Ciclosporin. Ciclosporin is already widely used for conditions like rheumatoid arthritis, psoriasis and the prevention of organ transplant rejection. It works by suppressing a type of immune cells that are responsible for inflammation in the spinal cord. We found evidence of improvement in the symptoms of HAM in the patients that were able to take the treatment for 6 months (10). This was an open observational study with no placebo and no comparison with other therapies.
In the next study we looked at Infliximab. This treatment blocks a protein, TNF, which causes inflammation and is damaging to nerves. As with the Ciclosporin study, patients with recent progression or less than 2 years of symptoms were eligible. Unfortunately we found infliximab to be poorly tolerated in patients with HAM and the study was discontinued. Further details are available at The ClinicalTrials.gov website under study number: NCT00823641.
Prednisolone is widely used to suppress inflammation in many organs, including the brain and spinal cord. We reviewed the notes of all patients treated with 3 day infusions of methyl prednisolone and found that although improvements in walking were short term pain was reduced for up to 6 months (11).
Inflammation in the brain
We have shown that inflammation in the brain can be detected using a new method of imaging called positron emission tomography with PBR28. We hope that this will help to speed up research on the treatment of HAM/TSP by allowing us to monitor changes with treatments directly (12).
NCHR was a participating centre in a study of the monoclonal antibody, called mogamulizumab, against a cell surface molecule called CCR4. CCR4 is found on the cell surface of ATL cells and HTLV-1 infected cells. Binding of mogamulizumab to CCR4 targets the cell to be killed by the patient’s immune system. The results of this trial have been reported at international conferences and published. Mogamulizumab is licensed for the treatment of ATL in Japan and appears to work best in the leukaemic form of ATL with little benefit for patients presenting with lymphoma.
Our research has been supported by:
• The European Community
• The Wellcome Trust
• The Jefferiss Trust
• The Medical Research Council
• National Institute for Health Research
• The Pain Society
9 Taylor G, Goon P, Furukawa Y, Green H, Barfield A, Mosley A, et al. Zidovudine plus lamivudine in Human T-lymphotropic virus type I-associated myelopathy: a randomised trial. Retrovirology. 2006;3:63.
10 Martin F, Adonis A, Fedina A, Gabriel C, Brodnicki E, Taylor G, et al. Ciclosporin for the treatment of patients with early or progressive ham: 24-week data from an open, pilot study. AIDS Res Hum Retroviruses. 2009;25(11):1199-281.
11 Buell KG, Puri A, Demontis MA, Short CL, Adonis A, Haddow J, et al. Effect of Pulsed Methylprednisolone on Pain, in Patients with HTLV-1-Associated Myelopathy. PLoS One. 2016;11(4):e0152557.
12 Dimber R, Guo Q, Bishop C, Adonis A, Buckley A, Kocsis A, et al. Evidence of brain inflammation in patients with Human T Lymphotropic Virus type 1 associated myelopathy (HAM): A pilot multi modal imaging study using [11C] PBR28 PET, MR T1w and DWI. J Nucl Med. 2016
The National Centre for Human Retrovirology Clinic Imperial College Healthcare NHS Trust, Ground Floor, Winston Churchill Wing, St Mary's Hospital, Praed Street, London W2 1NY