Inclusion Criteria:

1. Participant has provided informed consent. 2. Age 18-45 years. 3. Participant with CIS or MS at first presentation. 4. Participants show two or more lesions on T2 weighted MRI suggestive of demyelination. 5. Participant is willing and able to comply with clinical visits and procedures outlined in the study protocol.

Exclusion Criteria:

1. Hypersensitivity to Tysabri® or to any of the following excipients;

• - Sodium phosphate, monobasic, monohydrate.

• - Sodium phosphate, dibasic, heptahydrate.

• - Sodium chloride.

• - Polysorbate 80 (E433) - Water for injections.

2. Evidence of two or more chronic demyelinating hypo-intensities brain lesions 'black holes' on gadolinium-enhanced screening MRI. 3. Participants with increased risk for opportunistic infections, including immunocompromised participants (those currently receiving immunosuppressive therapies or those immunocompromised by prior therapies). 4. Combination with other Disease Modifying Treatments.. 5. Known active malignancies, except for participants with cutaneous basal cell carcinoma. 6. Implants such as pacemaker, aneurysm clip in the brain and MRI-incompatible prosthetic heart valves. 7. Significant comorbidities such as cardiac failure, renal failure, uncontrolled diabetes and uncontrolled hypercholesterolemia. 8. History of stroke, thrombosis and/or myocardial infarction. 9. Any other infection deemed, in the assessment of the PI or sub-investigator, clinically significant. 10. Claustrophobia. 11. Pregnancy or breastfeeding

MS is a disease of the central nervous system affecting over 130,000 people in the UK and more than 2.8 million worldwide. Left untreated, MS leads to chronic disability in the large majority of cases. CIS is a common first manifestation of MS: There is a more than 80% chance of MS in somebody presenting with CIS provided one or more "lesions" characteristic of inflammatory demyelination can be detected on a magnetic resonance imaging (MRI) of the brain. The presence of at least two such lesions is an inclusion criterion for this study. Inflammatory demyelination is the process by which cells of your body's own immune system attack the insulation sheath (= myelin) of nerve fibres (= axons) in the central nervous system. Once a diagnosis of MS has been confirmed, many people with this disease will be eligible for what is called "disease-modifying treatment" (DMT) on the NHS. Such treatment targets the immune cells that are involved in the inflammatory attack against the myelin sheaths and nerve fibres. However, while in a small number of cases, a diagnosis of MS can be made instantaneously it regularly takes week, months and, sometimes even longer, to fulfil the formal diagnostic criteria of MS. This diagnostic delay inevitably leads to delays in starting disease-modifying treatment. Using a trial concept geared towards rapid assessment of eligibility, and a disease-modifying treatment that is both highly effective and generally well tolerated in people with MS, AttackMS will test whether: (i) It is feasible to recruit participants with a diagnosis of CIS at high risk of MS, or definite MS, at first presentation for treatment within 14 days of symptom onset and (ii) Such early treatment improves myelin repair at 3 months, as measured using a special MRI technology called magnetisation transfer ratio (MTR). Natalizumab (Tysabri®) is a medication currently approved by the Medicines and Healthcare products Regulatory Agency (MHRA) as a disease-modifying treatment for adults with rapidly evolving severe (RES) relapsing MS. We are looking to test safety and efficacy of treatment with Tysabri® 300mg, given through a needle in a vein (intravenous infusion), over 20 weeks and to advance mechanistic understanding in treating people with first presentation of CIS or MS. AttackMS will test the effect of starting a highly-effective DMT licensed for MS, Tysabri®, within a short time

• - 14 days - after symptom onset.

The main objective is to test Tysabri®, given intravenously every 4 weeks over 20 weeks, for safety, efficacy, and to advance the mechanistic understanding of the earliest events in inflammatory demyelination/MS

Arms

Active Comparator: Tysabri® 300mg

Tysabri® 300mg, administered via intravenous infusion in a 4 week cycle, for a total of 6 cycles

Placebo Comparator: Placebo

Placebo, administered via intravenous infusion in a 4 week cycle, for 3 cycles, followed by Tysabri® 300mg, administered via intravenous infusion for a total of 3 cycles

Interventions

Drug: - Tysabri Injectable Product

Tysabri® is indicated as single disease modifying therapy in adults with highly active relapsing remitting multiple sclerosis. Tysabri® 300mg concentrate for solution for infusion and matching placebo are collectively referred to as IMP when detailing to blinded trial procedures. Tysabri® 300mg will be colourless, clear to slightly opalescent solution.

Drug: - Placebo

Placebo is colourless, clear to slightly opalescent liquid. The formulation of the is the same as that of commercial Tysabri® minus the active ingredient. Placebo is in the same containers/vials as Tysabri®.