Validation of the 18 kiloDalton Translocator Protein (TSPO) as a Novel Neuroimmunodulatory Target
This study investigates a protein called TSPO that exists in the brain and immune system cells. Researchers believe this protein may be a new target for treating multiple sclerosis, particularly the secondary progressive form where damage continues even when immune attacks have slowed.
Key Objective: The trial aims to validate whether TSPO can be used as a therapeutic target to reduce ongoing brain damage in secondary progressive multiple sclerosis.
Who to Consider: People with secondary progressive multiple sclerosis who are interested in exploring novel immune-modulating treatment approaches should consider this study.
Trial Parameters
Brief Summary
In multiple sclerosis (MS) cells of the immune system attack the brain causing tissue damage. In secondary progressive MS (SPMS) these repeated immune attacks have stopped but despite this new damage continues to appear. TSPO is a protein found in the brain and cells of the immune system, whose levels increase during MS. The investigators would like to know whether drugs that bind TSPO could dampen the immune responses in patients with SPMS. The investigators will be testing two drugs that affect TSPO; etifoxine and XBD173. Subjects with SPMS will be recruited from neurology clinics at hospitals associated with Imperial College Healthcare NHS Trust. Healthy volunteers will also be recruited in order to provide a comparison to these patients. The volunteers recruited will be invited to the clinical research facility (CRF) at Hammersmith Hospital. The volunteers will take one of the two drugs every day for 7 days. The researchers will perform blood tests before the first dose and after the last dose to investigate the effects of the drugs, including the expression of genes and immune cell activity. This will allow the researchers to explore which of the two drugs produces the greatest changes in the amount of TSPO in the blood in MS patients relative to healthy controls.
Eligibility Criteria
Inclusion Criteria: 1. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. 2. Aged 35-65 years old 3. A female subject is eligible to participate if she is a) of non-childbearing potential, defined as pre-menopausal females with a documented tubal ligation or hysterectomy, or postmenopausal defined as 12 months of spontaneous amenorrhea or b) of childbearing potential but not pregnant (as determined by urinary pregnancy test on screening and on each study day) and willing to use one of the contraception methods listed below 4. Male subject must agree to use one of the contraception methods listed above. 5. Willing to abstain from alcohol for the duration of dosing. 6. Expanded Disability Status Scale (EDSS) \>3.5 \<6.5 (SPMS patients only) Exclusion Criteria: 1. History of active neurological disease other than migraine or MS 2. Clinically meaningful abnormalities in routine bloods including: * eGFR \<