Dihexa for Multiple Sclerosis (MS): Cognitive Impairment, Remyelination & the 2026 UK Review

More than 150,000 people now live with multiple sclerosis in the UK — roughly one in every 440 people — and around half of them will at some point develop measurable MS cognitive impairment, the cluster of memory, attention and processing-speed symptoms patients call cog-fog. 2026 has already reshaped the field: NICE recommended natalizumab (Tysabri / Tyruko) for highly active RRMS in January, the UCLH AUTO1-MS1 CAR-T trial is recruiting in progressive MS, cladribine NHS access has been expanded, and the brain-penetrant BTK inhibitor tolebrutinib received an FDA Complete Response Letter in December 2025 despite a positive HERCULES Phase 3 in non-relapsing SPMS. Could a synaptogenic peptide that activates the HGF/c-Met system — the same axis identified by Bai and colleagues in Nature Neuroscience as the mediator of stem-cell-driven remyelination — have any role in MS? This is the rigorous 2026 UK evidence review, published ahead of World MS Day on 30 May 2026.

What Multiple Sclerosis Actually Is in 2026

Multiple sclerosis is a chronic, immune-mediated disease of the central nervous system in which lymphocytes — predominantly autoreactive T cells and B cells — cross the blood-brain barrier and trigger inflammatory demyelination of axons in brain and spinal cord. The classic neuropathology is the plaque — a focal area of demyelination, oligodendrocyte loss, axonal injury and astrogliosis — visible on MRI as the white-matter lesions that drive diagnosis. The 2017 McDonald criteria (and the 2024 update under review) require dissemination of lesions in space and time, supported by MRI and oligoclonal bands in cerebrospinal fluid.

The classical MS phenotypes are:

• Clinically isolated syndrome (CIS): a first inflammatory CNS event — optic neuritis, transverse myelitis, brainstem syndrome — that may or may not progress to MS.
• Radiologically isolated syndrome (RIS): incidental MS-like MRI lesions in someone without symptoms.
• Relapsing-remitting MS (RRMS): the dominant phenotype at diagnosis (~85%), characterised by acute attacks followed by partial or complete recovery.
• Secondary progressive MS (SPMS): the progressive phase that historically follows RRMS, often a decade or more after onset, with continued disability accumulation independent of relapses.
• Primary progressive MS (PPMS): ~10–15% of patients, characterised by gradual disability accrual from onset without an initial relapsing phase.

Two ideas dominate the 2026 conversation. The first is "smoldering" neuroinflammation — chronic low-grade microglial and B-cell activity in the CNS that drives disability progression independently of new MRI lesions. The second is the cognitive-impairment phenotype, increasingly recognised as a domain in its own right rather than a downstream side-effect of physical disability. Both ideas are why interest in compounds that act inside the CNS — including remyelinating, neuroprotective and synaptogenic agents — has grown sharply.

The UK Picture: 150,000+ People, Rising

Until 2020, the standard UK MS prevalence figure was around 109,000, derived from older General Practice Research Database analyses. A combined Public Health England / MS Society modelling exercise raised that estimate to over 130,000. The most recent MS Society UK estimate, published with the MS Trust, puts the figure at over 150,000 people living with MS in the UK — a roughly 13% rise on the 2019 number, with breakdowns of:

• England: ~105,450 people
• Scotland: ~15,750 (the highest national prevalence rate)
• Wales: ~5,600
• Northern Ireland: ~4,830

The increase is attributed to better case-finding, longer survival post-diagnosis with modern DMTs, and improved population data, rather than a change in underlying incidence. MS is approximately three times more common in women than men, has a peak incidence between ages 20 and 40, and is more prevalent at higher latitudes (Scotland's high rate fits that latitude gradient). UK prevalence translates to roughly one in every 440 adults.

That number matters for context. Compared with conditions covered elsewhere on this site — Parkinson's disease at ~153,000 UK patients, mild cognitive impairment with around 70,000 in the eligibility window for disease-modifying therapy, and Long COVID at ~2.1 million — MS sits as a high-burden, lifelong neurological disease with one of the most active drug-development pipelines in modern medicine.

MS Cognitive Impairment: The "Cog-Fog" Problem

For most of the 20th century MS was framed as a motor and sensory disease. Cognitive symptoms were dismissed as fatigue, depression, or peripheral. The modern picture is very different: 34–65% of people with MS have measurable cognitive impairment ([1], Fenu 2023 PMC review), with the prevalence rising as the disease progresses. The MS Society UK uses the working figure that around half of people with MS will at some point experience cog-fog.

Phenotypic prevalence varies meaningfully:

• CIS / RIS: 20–25%
• RRMS: 30–45%
• SPMS: 50–75%
• PPMS: 50–65%

The cognitive domains most consistently affected are:

• Information processing speed (most commonly impaired; the Symbol Digit Modalities Test is the standard screen)
• Episodic memory (verbal and visual learning)
• Sustained and divided attention
• Executive function (planning, working memory, response inhibition)
• Visuospatial processing

Language and basic IQ are typically preserved. The phenotype is not "dementia"; it is a subcortical-frontal pattern that maps onto the underlying disease biology — demyelinated long-range white-matter tracts, grey-matter atrophy, hippocampal involvement and synaptic dysfunction.

Comorbid depression, anxiety, MS-related fatigue and sleep disruption all worsen the cognitive picture independently — and are independently treatable. Treating those comorbidities is one of the highest-yield steps available in 2026 NHS MS care.

The HGF / c-Met Story in MS: Why Dihexa Fits the Diagram

This is the section where the mechanistic case for Dihexa in MS is at its strongest. It is also the section where the "mechanistic plausibility is not clinical evidence" caveat must be loudest.

Hepatocyte growth factor (HGF) is a pleiotropic cytokine produced by mesenchymal cells throughout the body, including astrocytes and certain neural progenitors in the CNS. Its receptor, c-Met (encoded by the MET proto-oncogene), is expressed on neurons, oligodendrocytes, astrocytes, and microglia. The mechanism of action page covers Dihexa's pharmacology in depth; in summary, Dihexa is an angiotensin IV-derived hexapeptide whose synaptogenic action in primary hippocampal neuron cultures was shown by Benoist 2014 to be dependent on HGF/c-Met activation ([2]). It is, pharmacologically, a c-Met agonist mediated through the angiotensin IV / IRAP / HGF axis.

The foundational paper: Bai 2012, Nature Neuroscience

In Bai and colleagues' 2012 paper in Nature Neuroscience ([3]), the Tulane and Cleveland Clinic teams set out to ask which molecule was responsible for the well-documented benefit of mesenchymal stem cell (MSC) administration in MS animal models. By systematically fractionating MSC-conditioned medium and testing functional activity, they identified HGF as the primary mediator of MSC-induced recovery in experimental autoimmune encephalomyelitis (EAE). Critically:

• Systemic recombinant HGF treatment markedly accelerated remyelination in lysolecithin-induced rat dorsal spinal cord lesions and in slice cultures.
• HGF-containing MSC-conditioned medium increased the proportion of oligodendrocyte lineage cells and neurons in slice culture.
• HGF treatment increased myelin basic protein (MBP) labelling, increased NG2+ oligodendrocyte progenitor cells, and decreased GFAP astrocyte reactivity in lesion areas.
• Anti-c-Met antibody blocked the recovery, confirming the receptor dependence.

This is the foundational evidence that HGF/c-Met activation is, biologically, a candidate remyelination strategy in MS. It does not prove that Dihexa, an oral peptide, achieves the central HGF/c-Met activation required at the lesion. It does mean the target is real.

CSF HGF correlates with MS disease activity

Tsareva 2012 and subsequent groups have shown that cerebrospinal fluid HGF levels correlate negatively with MS disease activity ([4]). Patients with active disease have lower CSF HGF; patients in remission have higher CSF HGF. The directionality is consistent with HGF acting as an endogenous anti-inflammatory and pro-regenerative cytokine that is depleted during active demyelination. This is biological, not pharmacological, but it strengthens the rationale for HGF/c-Met as a therapeutic target.

Interferon-beta induces HGF

Independently, Benkhoucha 2012 (PLOS ONE) demonstrated that interferon-beta — one of the original MS DMTs — induces HGF expression in monocytes from MS patients ([5]). One mechanism through which an established MS therapy works is, at least in part, by raising endogenous HGF. That observation is not Dihexa-specific, but it is supportive evidence that pharmacological HGF augmentation is part of the MS treatment story.

Oligodendrocyte progenitor cell biology

Modern remyelination biology identifies oligodendrocyte progenitor cells (OPCs) as the cellular target. OPCs are abundant in adult CNS but typically fail to differentiate and remyelinate at MS plaques, particularly in chronic and progressive disease. The 2025 "Road to Remyelination in MS" review ([6]) catalogues the various OPC-targeting strategies in development, including LINGO-1 inhibition (opicinumab), retinoid receptor agonists (bexarotene), thyroid mimetics, antimuscarinics (clemastine), and growth factor support (HGF among them). None has yet achieved Phase 3 success as a remyelinator. The HGF axis is therapeutically attractive precisely because it is both pro-OPC differentiation and immunomodulatory, addressing two pieces of the MS lesion biology simultaneously.

Synaptopathy in MS cognitive impairment

The MS cognitive picture is increasingly understood as a synaptopathy as well as a demyelinating disease. Grey-matter lesions, hippocampal and thalamic synapse loss, and impaired long-term potentiation have all been demonstrated in MS post-mortem and on advanced imaging. A synaptogenic peptide that increases dendritic spine density — Dihexa's signature effect in animal cognitive models — is at least conceptually aligned with the cognitive lesion. That is not the same as evidence that it works.

Putting these pieces together: the HGF/c-Met system has independent biological support in (1) remyelination, (2) anti-inflammatory immunomodulation, and (3) synaptogenesis. All three are deficits in MS. That is the strongest mechanistic case for any peptide in MS today — and it is still mechanistic, not clinical.

The 2026 UK MS Treatment Landscape

For UK readers, the most important context for thinking about any new compound is the existing NHS treatment pathway. 2026 has been an unusually busy year for MS therapeutics.

January 2026: NICE recommends natalizumab (Tysabri / Tyruko)

In January 2026, NICE recommended natalizumab — both Biogen's Tysabri (originator) and Sandoz's Tyruko (biosimilar) — for adults with highly active relapsing-remitting MS that remains active after at least one disease-modifying therapy and for whom cladribine is not suitable ([7]). The originator can be given as a subcutaneous injection (the value-for-money formulation NICE recommends), and the biosimilar as an infusion.

Natalizumab is an α4-integrin antibody that prevents lymphocytes from crossing the blood-brain barrier into the CNS. It is highly effective on relapse rate and MRI activity, and unusually it can be continued during pregnancy — an important consideration in a disease that disproportionately affects women of child-bearing age. Its main constraint is the risk of progressive multifocal leukoencephalopathy (PML), a rare but potentially fatal JC virus-driven brain infection, which requires JCV antibody status testing before and during treatment.

Cladribine NHS access expanded

NICE has expanded access to oral cladribine (Mavenclad) for adults with active relapsing remitting MS who would otherwise be offered highly effective DMTs. England is now the first European healthcare system to widely offer the at-home tablet for active MS, with an estimated 2,000 additional people expected to benefit over three years (MS Trust, [8]). Cladribine works by selectively depleting lymphocytes through a short oral course given over two weeks per year, with many people not requiring further DMTs for four years.

Ocrelizumab (Ocrevus) home injections

Anti-CD20 B-cell depletion with ocrelizumab is a mainstay of high-efficacy MS therapy and the only DMT licensed in the UK for primary progressive MS. NHS England has rolled out a subcutaneous formulation that cuts the hospital treatment time by approximately 90%, with NHS Tayside in Scotland offering home administration as an option in 2026 ([9]). Ocrelizumab broadly resembles its sister antibody ofatumumab (Kesimpta) and rituximab in mechanism.

UCLH AUTO1-MS1: the UK's first MS CAR-T trial

In October 2025, UCLH treated the first UK MS patient with chimeric antigen receptor (CAR) T-cell therapy. The trial, AUTO1-MS1, is led by Dr Wallace Brownlee at the National Hospital for Neurology and Neurosurgery and tests obecabtagene autoleucel (obe-cel) — a second-generation anti-CD19 CAR-T originally developed for B-cell malignancies, with reduced cytokine-release-syndrome toxicity — in people with progressive MS ([10]). The therapy modifies the patient's own T cells to deplete B cells, conceptually attempting an immune reset rather than ongoing modulation. The trial aims to recruit up to 18 patients globally by early 2027 and represents one of the most significant translational MS programmes of the decade. It is not Dihexa-related; it is part of the context that frames any new MS conversation.

Tolebrutinib: HERCULES success, FDA setback

The brain-penetrant BTK inhibitor tolebrutinib targets the "smoldering" neuroinflammation in chronically activated microglia and B cells. The Phase 3 HERCULES trial in non-relapsing secondary progressive MS (nrSPMS) reported a 31% delay in time to confirmed disability progression versus placebo — the first Phase 3 positive result in nrSPMS (Progressive MS Alliance, [11]). However, the FDA issued a Complete Response Letter in December 2025, declining the regulatory submission for nrSPMS pending further data; the parallel Phase 3 in primary progressive MS missed its primary endpoint and Sanofi will not pursue PPMS registration. The story is mixed but important: a real signal in smoldering inflammation, an unresolved regulatory and safety profile (hepatotoxicity has been a recurring BTK-inhibitor concern), and uncertain UK availability.

The established DMT toolkit

Beyond the 2026 news, the established UK MS DMT toolkit includes:

• Self-injected: interferon-beta-1a/1b (Avonex, Rebif, Plegridy, Betaferon), glatiramer acetate (Copaxone), ofatumumab (Kesimpta).
• Oral: dimethyl fumarate (Tecfidera), diroximel fumarate (Vumerity), teriflunomide (Aubagio), fingolimod (Gilenya), siponimod (Mayzent), ozanimod (Zeposia), ponesimod (Ponvory), cladribine (Mavenclad).
• Infused: natalizumab (Tysabri), ocrelizumab (Ocrevus), alemtuzumab (Lemtrada).
• Autologous haematopoietic stem cell transplant (AHSCT): increasingly recognised in highly active RRMS unresponsive to high-efficacy DMTs.

Selection between these is a complex neurological decision involving disease activity, disability, MRI burden, JCV serology, family planning, comorbidities and patient preference — the kind of decision an MS clinical nurse specialist and consultant neurologist make together, supported by NHS England's national treatment algorithm.

Importantly: none of the above DMTs target MS cognitive impairment as a primary endpoint. Ocrelizumab and high-efficacy DMTs slow cognitive decline as a downstream consequence of slowing disease activity, but no licensed MS drug exists primarily to treat cog-fog. That is the treatment-gap that any cognitive-focused intervention — pharmacological, behavioural or unproven — is implicitly aiming to fill.

Where Dihexa Sits in the MS Picture

If you took the MS lesion biology and asked "what theoretical pharmacology would address most of this", a small-molecule HGF/c-Met agonist with CNS penetration that drove synaptogenesis, supported OPC differentiation and reduced microglial activation would be a coherent answer. Dihexa — on paper — is in that conceptual space. The chemistry is in the Dihexa vs BDNF page; the broader pharmacology in mechanism of action.

What Dihexa is not, in 2026, is a tested treatment for any aspect of multiple sclerosis. There is:

• No human trial of Dihexa in MS, MS cognitive impairment or remyelination.
• No published case series of MS patients using Dihexa.
• No pharmacovigilance dataset on combination with any DMT.
• No EAE or other in vivo MS-model data with Dihexa specifically (as opposed to recombinant HGF, which has the Bai data).
• No safety study in immunosuppressed patients.

The closest a c-Met-axis cognition compound has come to clinical proof is fosgonimeton (ATH-1017), the small-molecule HGF positive modulator developed by Athira Pharma. It missed its primary endpoint in Alzheimer's disease (LIFT-AD) and is now being evaluated in Parkinson's disease dementia and dementia with Lewy bodies (SHAPE) with mixed early signals. Importantly, fosgonimeton has not been developed for MS. There is no late-stage HGF/c-Met-targeted compound currently in MS clinical development.

The mechanistic story is real. The MS clinical story does not exist.

DMT Interactions: Why Combining Is Not a Trivial Question

This is the most under-discussed safety question in any conversation about Dihexa and MS. Modern MS DMTs are sophisticated immunological tools and several of them have specific concerns that interact non-obviously with a HGF/c-Met agonist:

• Natalizumab and PML risk. Anti-α4-integrin therapy carries JC virus reactivation risk in the CNS. HGF/c-Met has roles in monocyte trafficking and microglial regulation. There are no studies of HGF augmentation under natalizumab. Adding any unscheduled immunomodulator to a JCV-positive natalizumab regimen is a meaningful unknown.
• Anti-CD20 (ocrelizumab, ofatumumab, rituximab) and infection risk. Sustained B-cell depletion increases susceptibility to respiratory and opportunistic infection. HGF has both pro-regenerative and immunomodulatory effects; the net effect under anti-CD20 in humans is untested.
• Cladribine immune reconstitution. The two-week-per-year cladribine course produces sustained lymphopenia followed by reconstitution. Adding any immunomodulator during the lymphopenic window is non-trivial.
• S1P modulators (fingolimod and family) and macular oedema, hepatotoxicity, bradycardia. No interaction studies with HGF agonism.
• Fumarates (dimethyl, diroximel) and GI / hepatic side-effects. No interaction studies.
• Interferon-beta and HGF induction. Interferon-beta itself induces HGF in monocytes (Benkhoucha 2012). The pharmacological direction overlaps with Dihexa's; the additive effect, if any, is unstudied.
• Tolebrutinib (where available) and BTK-inhibitor hepatotoxicity. Adding any compound to a BTK inhibitor with documented hepatic safety questions is specifically inadvisable.

The pragmatic position is unambiguous: do not combine Dihexa with any MS DMT without explicit input from your treating neurologist — and your treating neurologist will not have the controlled human safety data they would require to support that combination. The DMT regimen your neurologist has selected for you is the most evidence-rich element of your MS care; it should not be compromised.

What Actually Works for MS Cognitive Impairment in 2026

The cog-fog evidence base is imperfect but real, and the interventions are accessible.

Cognitive rehabilitation

The strongest behavioural evidence base is for computerised cognitive rehabilitation (BrainHQ, RehaCom) and compensatory strategy training (external memory aids, structured task management, attention-pacing). Effect sizes are modest but reproducible and durable. The MS Trust and MS Society both recommend cognitive rehabilitation pathways and several specialist NHS MS services offer neuropsychology referral.

Exercise and physical rehabilitation

Aerobic exercise raises BDNF and IGF-1, reduces systemic inflammation, supports hippocampal volume, and improves mood and fatigue — all of which independently improve MS cognition. The MS Society's Move programme, MS Trust resources and MS-aligned physiotherapy services support graded exercise prescription. Heat sensitivity (Uhthoff phenomenon) needs accommodation but does not contraindicate exercise.

Treat the comorbidities

MS cognitive impairment rarely exists in isolation. Treating comorbid depression, anxiety, MS-related fatigue and sleep disruption reliably improves measured cognition, often more substantially than any direct cognitive intervention. SSRIs and CBT for MS depression are well-evidenced; amantadine and modafinil for MS fatigue have supportive RCTs; pregabalin and gabapentin manage neuropathic pain that itself disrupts cognition.

Optimise the DMT

The single most powerful long-term cognitive-protection step in MS is effective disease-modifying therapy that controls inflammatory activity early. Higher-efficacy early treatment (anti-CD20, natalizumab, cladribine, alemtuzumab) is increasingly favoured precisely because it preserves long-term cognition better than escalation from low-efficacy DMTs. If MS cognitive impairment is your primary concern, the DMT conversation with your neurologist is the most important conversation.

Vascular health, sleep, diet

MS coexists with the same vascular and metabolic risk factors that drive cognitive ageing in the general population. Blood pressure, glycaemic and lipid control; Mediterranean / MIND-style diet; alcohol moderation; smoking cessation; and consistent sleep all add modest, additive cognitive protection. The brain aging review covers the Lancet Commission's 14 modifiable risk factors framework, much of which applies in MS.

Where does Dihexa actually sit?

In a hypothetical world where Dihexa had a controlled human trial in MS cognitive impairment with clear benefit, no DMT-interaction signal and no safety concern, it would be positioned as a structural-recovery adjunct alongside cognitive rehabilitation and exercise. We do not live in that world. In 2026 the appropriate position is: not a treatment, not a recommendation, and a meaningful safety unknown in a population that is often already on multiple immunomodulatory drugs.

Who Should Particularly Not Consider Dihexa for MS

The list of contraindications for people with MS is broader than for the general population:

• Anyone on any MS DMT, regardless of class, without explicit input from their neurologist (which is unlikely to support an unscheduled HGF/c-Met agonist).
• Anyone JCV-positive on natalizumab — the PML risk profile should not be perturbed by unstudied immunomodulation.
• Anyone within an induction window of cladribine, alemtuzumab or AHSCT.
• Anyone with active hepatitis B or C, or known hepatic dysfunction.
• Anyone pregnant, breastfeeding or trying to conceive — MS disproportionately affects women in their reproductive years and most DMTs already require careful family-planning coordination.
• Anyone with a personal or strong family history of cancer, given c-Met's recognised role as a proto-oncogene (covered in detail in the chemo brain review).
• Anyone with a known MET-driven tumour in their personal or family history.
• Anyone with active or recurrent infection, particularly opportunistic or atypical infection on a DMT.
• Anyone with poorly controlled MS who has not exhausted regulated DMT escalation through the NHS pathway.
• Anyone whose neurologist or MS specialist nurse has not been consulted.

For people with MS who want to engage with the underlying biology, the highest-yield interventions remain exercise, sleep optimisation, treating comorbid mood and anxiety, cognitive rehabilitation, and ensuring the DMT regimen is optimal — all of which engage the same upstream pathways that motivate interest in synaptogenic peptides, with much better safety profiles.

Community Reports: What People With MS Say Online

Online reports from people with MS who have tried Dihexa are sparse, anecdotal and uncontrolled. The available pattern from forum posts and personal accounts:

• A small number of people with relapsing-remitting MS describe subjective improvements in word-finding and processing speed within four to six weeks — almost always alongside continued DMT use.
• A smaller number describe no perceptible benefit or attribute change to time, exercise, or sleep that improved in parallel.
• Vivid dreams and altered sleep architecture are reported as consistently in MS users as in the general user base — covered in the sleep and memory consolidation review.
• A minority report worsened fatigue or paradoxical agitation in the first one to two weeks.
• No relapse acceleration or DMT-failure signals have been reported in the (very limited) public anecdote pool — but absence of reports in a small uncontrolled population is not the same as safety, and any new MRI activity in someone using an unscheduled compound during DMT is a confound their neurology team would struggle to interpret.

This is not data. It is anecdote. It is included only because it is what readers will find online and we would rather contextualise it honestly than ignore it.

Dosing and Practical Context (For the Specific Sub-Group This Applies To)

If, having read the safety section in full, an adult with MS who is not in any of the contraindicated groups still wants to use Dihexa as a research compound, the general dosing and stacking guidance lives on the dedicated dosage and stacking guide pages and is not duplicated here. The points specific to the MS conversation:

• The therapeutic logic, if any, is structural — weeks-to-months timeframes, not acute symptomatic dosing.
• Cycling matters; sustained continuous c-Met activation in immunosuppressed patients is one of the long-term safety unknowns.
• Dihexa-specific symptoms (vivid dreams, altered sleep, occasional headache, transient irritability) are covered on the side effects page and may be hard to disentangle from MS fatigue, sleep disruption and cognitive symptoms.
• Heat sensitivity (Uhthoff phenomenon) and exercise tolerance should not be neglected; sleep hygiene and circadian timing of dosing are particularly important in MS.
• Any new neurological symptom, vision change, or relapse-like episode while using an unscheduled compound during DMT must be reported to the MS service immediately.
• Stacking with stimulants, fatigue medications (modafinil, amantadine), or any other unscheduled compound multiplies the interpretation problem.

None of this constitutes a recommendation. The appropriate clinical pathway for MS, including MS cognitive impairment, is in the evidence-based section above.

World MS Day 2026 and the “My MS Diagnosis” Campaign

World MS Day 2026 falls on Friday 30 May. The campaign theme for 2024–2026 is My MS Diagnosis: navigating MS together ([12]), advocating for early and accurate diagnosis worldwide. The campaign explicitly highlights barriers to MS diagnosis — including diagnostic delay for cognitive symptoms, paediatric MS, and people in lower-resource settings — and calls for better MS training and awareness amongst healthcare professionals.

The relevance for this article: MS cognitive impairment is one of the most under-diagnosed aspects of MS. Patients commonly raise it; routine neurology follow-up is not always equipped to assess it; and the cognitive deficit can predate physical disability by years in some phenotypes. The MS Society and MS Trust both lobby for cognitive screening to become standard. If reading this article prompts a UK reader to have a more direct cog-fog conversation with their MS team, the article has earned its place in the World MS Day moment, regardless of what they conclude about Dihexa.

The Bottom Line in 2026

Multiple sclerosis is a high-burden, lifelong neurological disease in which two distinct biological problems — demyelination and synaptopathy — produce both physical disability and cognitive impairment. The HGF/c-Met system has independent biological evidence in remyelination (Bai 2012, Nature Neuroscience), in immunomodulation (Benkhoucha 2012), and in synaptogenesis (Benoist 2014). All three are areas of unmet need in MS. CSF HGF inversely correlates with MS disease activity. None of this constitutes evidence that Dihexa, an oral angiotensin IV-derived peptide that pharmacologically activates HGF/c-Met, helps any aspect of MS in humans.

2026 has produced one of the most active years in MS therapeutics in a decade. NICE has recommended natalizumab (Tysabri / Tyruko) for highly active RRMS. Cladribine NHS access has been expanded. Ocrelizumab home injections are rolling out. The UCLH AUTO1-MS1 CAR-T trial is recruiting. Tolebrutinib has shown a positive HERCULES Phase 3 in nrSPMS but received an FDA Complete Response Letter. None of these target MS cognitive impairment as a primary endpoint — the cog-fog gap remains real.

The right answer in 2026, for someone with MS reading this article, is:

1. Recognise MS cognitive impairment as a real and assessable condition. Around half of people with MS will experience it; it is not in your imagination.
2. Raise it explicitly with your MS team. Ask for cognitive screening; ask about referral to neuropsychology if symptoms are functionally limiting; the World MS Day diagnosis theme exists for a reason.
3. Optimise your DMT. Effective disease control early is the single most important long-term cognitive protector. The 2026 NHS treatment landscape is broader than at any previous point.
4. Engage the strongest evidence-based interventions: cognitive rehabilitation, graded exercise, treatment of comorbid depression, anxiety, fatigue and sleep disruption.
5. Use the UK patient organisations: the MS Society, MS Trust, MS-UK and Shift.ms have some of the best patient information in the world.
6. Treat Dihexa, in the MS population specifically, as a compound whose theoretical fit is good, whose human evidence does not exist, and whose interaction with established DMTs is unstudied — not a treatment.

The bigger conclusion is that the MS evidence base is moving in a direction where the HGF/c-Met-axis hypothesis will eventually be tested cleanly — whether through stem-cell-derived HGF augmentation, recombinant HGF, or a CNS-penetrant small molecule. That work is not yet done in MS. Reading this page, exercising, sleeping, optimising your DMT and asking your MS service about cognitive assessment is the rational 2026 plan.

Frequently Asked Questions

Can Dihexa help multiple sclerosis?

No human trial, no case series, no MS pharmacovigilance dataset. The mechanistic fit through HGF/c-Met is real (Bai 2012, Benoist 2014) but does not constitute clinical evidence. UK MS care should run through the NHS MS service, your neurologist and MS clinical nurse specialist.

Could Dihexa promote remyelination in MS?

The biology is genuine: HGF/c-Met activation supports oligodendrocyte progenitor cells and remyelination in lysolecithin and EAE models, and HGF was identified as the active mediator of mesenchymal-stem-cell recovery in MS animal models (Bai 2012, Nature Neuroscience). Whether oral Dihexa achieves the relevant central HGF/c-Met activation, and whether that translates to remyelination in human MS, is untested. No remyelinator has yet been licensed for MS.

How common is cognitive impairment (cog-fog) in MS?

34–65% of people with MS depending on phenotype and assessment method, with the MS Society UK using a working figure of around 50%. Prevalence is highest in secondary progressive MS (50–75%) and lowest in CIS / RIS (20–25%). Processing speed, episodic memory, attention and executive function are the most affected domains.

What is the UK MS treatment landscape in 2026?

NICE recommended natalizumab (Tysabri, Tyruko) for highly active RRMS in January 2026. Cladribine NHS access has been expanded. Ocrelizumab home injections have rolled out. The UCLH AUTO1-MS1 CAR-T trial began October 2025 in progressive MS. Tolebrutinib received an FDA Complete Response Letter in December 2025 despite a positive HERCULES Phase 3 in nrSPMS.

What did the Bai 2012 paper show?

Mesenchymal stem cell-induced recovery in EAE is mediated by HGF, and systemic recombinant HGF accelerated remyelination in lysolecithin-induced spinal cord lesions. Anti-c-Met antibody blocked the recovery. This is the foundational evidence that HGF/c-Met activation is a candidate remyelination strategy in MS.

Can Dihexa be combined with disease-modifying therapy for MS?

There are no interaction studies with any MS DMT. Several DMTs are profoundly immunosuppressive and have specific PML, opportunistic infection, hepatic or cardiac considerations. Adding an unscheduled HGF/c-Met agonist to a DMT regimen has no controlled human safety data and is not pharmacologically defensible.

Is Dihexa safe in MS-related immunosuppression?

Unknown. HGF has both pro-regenerative and immunomodulatory effects. The risk profile under sustained DMT-driven immunosuppression has not been established in any controlled human study.

Does Dihexa help MS fatigue?

No fatigue trials. MS fatigue is multifactorial; the strongest evidence-based interventions are graded exercise, CBT, treatment of comorbid depression and sleep disorders, and pharmacological options including amantadine and modafinil.

What is the UCLH CAR-T MS trial?

AUTO1-MS1, the first UK MS CAR-T trial, testing obecabtagene autoleucel (obe-cel) anti-CD19 CAR-T in progressive MS. Led by Dr Wallace Brownlee at UCLH; first UK patient treated October 2025; aims to recruit up to 18 patients globally by early 2027.

What happened with tolebrutinib?

Sanofi's brain-penetrant BTK inhibitor showed a 31% delay in disability progression in the Phase 3 HERCULES trial in non-relapsing SPMS, but received an FDA Complete Response Letter in December 2025. The PPMS Phase 3 missed its endpoint and Sanofi will not pursue PPMS registration. UK availability is currently uncertain.

Is Dihexa legal in the UK as an MS treatment?

Dihexa is not a licensed medicine and is not approved by the MHRA. It is not a controlled drug under the Misuse of Drugs Act, but marketing or supplying it as an MS treatment would breach UK medicines and advertising regulation. See the UK legal status page for the full position.

When is World MS Day 2026?

Friday 30 May 2026. The 2024–2026 campaign theme is My MS Diagnosis: navigating MS together, advocating for earlier and more accurate diagnosis worldwide.

Selected References & Outbound Sources

1. Fenu G et al. Cognitive impairment in multiple sclerosis: clinical management, MRI, and therapeutic avenues. PMC, 2023.
2. Benoist CC et al. The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor / c-Met system. J Pharmacol Exp Ther, 2014.
3. Bai L et al. Hepatocyte growth factor mediates mesenchymal stem cell-induced recovery in multiple sclerosis models. Nature Neuroscience, 2012.
4. Tsareva E et al. Cerebrospinal hepatocyte growth factor levels correlate negatively with disease activity in multiple sclerosis. 2012.
5. Benkhoucha M et al. Interferon-beta induces hepatocyte growth factor in monocytes of multiple sclerosis patients. PLOS ONE, 2012.
6. The Road to Remyelination in Multiple Sclerosis. PMC review. 2025.
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