DMSO and Neurology

Parkinson’s Disease

Parkinson’s disease results from the progressive loss of dopamine-producing neurons in the substantia nigra. Research in this field was revolutionized in the early 1980s when recreational drug users who injected a badly synthesized synthetic heroin rapidly developed severe Parkinson’s-like symptoms due to it being contaminated with MPTP, an agent whose active metabolite (MPP+) specifically targeted those neurons, making it possible to reliably model Parkinson’s in laboratory animals. This was followed by the realization one herbicide (paraquat) was very similar to MPP+, another pesticide (rotenone) causing similar damage to neurons, a variety of pesticides being linked to a higher risk of Parkinson’s (such as organophosphates), and 6-OHDA also being able to reliably create Parkinson’s.
Note: one of the major challenges with glyphosate (Roundup) is that while it is toxic, the herbicides it replaced like paraquat are much more toxic.

Numerous studies have shown that DMSO directly counteracts the neurotoxicity of these Parkinson’s-producing agents (e.g., in the organophosphate studies mentioned previously, DMSO repeatedly reduced mortality, accelerated organophosphate detoxification, and protected neuromuscular function). Most remarkably, a case-control study of young-onset Parkinson’s disease (63 cases, 68 controls) found that individuals with Parkinson’s were one tenth as likely to have been exposed to DMSO as normal controls, suggesting DMSO has protective qualities that confer a roughly 10-fold reduction in disease risk. In contrast, the same study found insecticide exposure increased risk nearly 6-fold, fumigated housing over 5-fold, and herbicide exposure over 3-fold — results consistent with the extensive epidemiological literature linking pesticide exposure to Parkinson’s.
Note: this study also found smoking was associated with reduced PD risk, a finding that aligns with decades of epidemiological evidence linking nicotine exposure to lower PD incidence, lending credibility to the study’s methodology.

DMSO has directly demonstrated neuroprotective effects in multiple Parkinson’s models. In animals, DMSO suppressed hydroxyl radical-induced nigrostriatal injury from MPTP,^1,2,3,4 and in rotenone-induced Parkinson’s rats, DMSO improved hippocampal CA1 and CA3 neuron morphology, restoring pyramidal cells and Nissl bodies damaged by rotenone and normalizing their electrical activity. DMSO also protected astrocytes from MPP+-induced toxicity by reducing lipid peroxidation and metabolic impairment, protected glial glutamine synthetase from MPP+-induced hydroxyl radical damage, protected human SH-SY5Y neuroblastoma cells from 6-OHDA-induced cytotoxicity, and reduced both lipid peroxidation and protein carbonyl formation in rat brain homogenates from ferrous chloride or hydrogen peroxide, and separately reduced hydroxyl radical production during 6-OHDA autoxidation and the formation of hydroxylated dopamine products.^1,2
Note: in one mouse study, intraperitoneal DMSO did not protect against MPTP-induced dopamine depletion, indicating its neuroprotective effects may depend on the route, timing, or dose of administration.

Interestingly, DMS (DMSO’s naturally occurring, odor-producing metabolite) at near-physiological concentrations also protected neurons against both 6-OHDA and MPP+-induced apoptosis, with this effect being dependent upon MsrA (the enzyme that converts DMS to DMSO), suggesting the endogenous DMS-DMSO cycle functions as part of the body’s natural antioxidant defense against dopaminergic neurodegeneration.^1,2 This, in turn, raises an interesting conundrum as I have received a few reports of Parkinson’s patients who had dramatic responses to DMSO who then stopped due to the odor impeding sexual relations with their spouse, and my first thought was to recommend a low odor DMSO formulation (discussed here), but if DMS plays a key therapeutic role in Parkinson’s disease, that approach may not be viable.
Note: that study also found DMS protected against H₂O₂-induced lipid peroxidation and antimycin A generated super oxide production.

Additionally, DMSO reversed rotenone’s complete blockade of microtubule assembly from purified tubulin in vitro — a finding with direct relevance to Parkinson’s, as microtubule disruption impairs axonal transport and contributes to dopaminergic neuron death. Likewise, a Russian physical therapy monograph recommended topical DMSO novocaine compresses for neurological conditions including Parkinson’s, and a patent proposed DMSO as a transdermal enhancer for a botulinum toxin patch to treat the spasticity associated with Parkinson’s, cerebral palsy, dystonia, and multiple sclerosis.
A vast number of agents in combination with DMSO have also shown therapeutic benefit in Parkinson’s models.

Curcumin protected nigral dopaminergic neurons, reduced iNOS and glial activation, and upregulated neuroprotective pathways (IGF-1/Akt/FoxO3a).^1,2

Paeoniflorin repeatedly reduced α-synuclein expression, decreased Lewy body formation, and protected dopaminergic neurons across multiple studies,^1,2 It also inhibited microglial overactivation, increased BDNF and GDNF secretion, and promoted neural stem cell differentiation into dopaminergic neurons.¹

Icariside II induced human amniotic mesenchymal stem cells to differentiate into dopaminergic neuron-like cells (optimal at 3–10 μmol/L via PI3K signaling). In another protocol DMSO helped differentiate iPSCs into dopaminergic progenitors for PD stem cell therapy.

Ginsenosides Rg1 and Rg3 both significantly attenuated dopaminergic neuron loss, neuroinflammation, and α-synuclein accumulation.^1,2,3,4

Geniposide reduced α-synuclein levels and prevented dopaminergic neuron loss by modulating the miR-21/LAMP2A axis, while ginkgolide B similarly reduced α-synuclein expression via the related miR-207/LAMP2A pathway.^1,2 Ambroxol increased β-glucocerebrosidase activity and reduced α-synuclein oligomer levels, restoring cell viability and mitochondrial function in dopaminergic neurons. Polyphenols reduced seeded α-synuclein aggregation via NRF2-mediated antioxidant responses. Carnosic acid attenuated 6-OHDA neurotoxicity by upregulating parkin and restoring proteasomal clearance of ubiquitinated proteins in cellular and animal PD models.

L-sulforaphane dissolved in DMSO activated the NRF2 pathway in Parkinson’s disease patient-derived cells, restoring their deficient glutathione levels — one of the only studies using actual patient cells.

Most uniquely, NAMI-A — a low-toxicity ruthenium-DMSO complex — inhibited α-synuclein aggregation and membrane interactions with submicromolar affinity, disassembled pre-formed fibrils, abolished α-synuclein cytotoxicity toward neuronal cells, and mitigated neurodegeneration and motor impairments in a rat Parkinson’s model, providing a novel basis for designing ruthenium-DMSO complexes that target α-synuclein-driven pathology through a mechanism distinct from organic agents.

In MPTP models, tanshinone IIA preserved approximately 75% of dopaminergic neurons while reducing microglial activation; tetramethylpyrazine prevented motor deficits and neuron loss via the Nrf2 pathway; 6-Hydroxy-1H-indazole protected 90-93% of dopaminergic neurons from death; baicalein dose-dependently reduced rotation behavior (a key indicator of motor impairment), neuroinflammation, and dopaminergic neuron apoptosis via Wnt/β-catenin; neferine improved mouse motor disorders and reduced neuroinflammation and α-synuclein in the substantia nigra; SB239063 (a p38 MAPK inhibitor) protected TH-positive neurons; NESS 0327 (a CB1 receptor antagonist) ameliorated motor deficits; novel c-Abl kinase inhibitors outperformed nilotinib in blocking MPP+-induced apoptosis; GW5074 prevented TH-positive neuron loss in mice genetically engineered to have PD. In nigrostriatal pathway injury mice, both ERK inhibition (U0126) and PDGFRα inhibition (AG1296) reduced glial activation and scarring, with U0126 also improving long-term neurobehavioral outcomes.

In LPS-induced PD mice, pazopanib protected dopaminergic neurons by suppressing TNF-α, PGE2, and IL-6 via MEK4-JNK-AP-1 signaling, while rapamycin reduced neuroinflammation by enhancing microglial lipid metabolism.

NBP (a Chinese stroke medication) rescued dopaminergic neurons by 30% and striatal dopamine terminals by 49%. Carvacrol (found in oregano and thyme oils) was neuroprotective via TRPC1 inhibition in dopaminergic neurons and TRPA1 activation in astrocytes. Dasatinib and resveratrol in combination improved learning, memory, motor coordination, and reduced anxiety. MOTS-c improved motor function, reversed TH-positive neuron loss, and activated the Nrf2/Keap1 antioxidant pathway in rotenone PD rats. Puerarin mitigated rotation behavior and upregulated DAT, VMAT2, and TH in rotenone PD rats. A caspase inhibitor reduced neuron loss and improved rotation behavior in 6-OHDA rats, though blocking apoptosis triggered compensatory glial necroptosis.

Shuimuheningfang improved motor and non-motor symptoms in 80 PD patients and reduced α-synuclein in model mice,^1,2 while Compound Dihuang Granules (with a JNK inhibitor) reduced rotation behavior and protected dopaminergic neurons in 6-OHDA rats.

In C. elegans PD models, olive leaf extract strongly protected dopaminergic neurons from 6-OHDA toxicity (up to ~56% less degeneration), while oleuropein, oleanolic acid, tyrosol, 3-hydroxytyrosol, saffron, Polygonum multiflorum, and Ziziphus jujuba each also provided significant protection.

Additional agents showing neuroprotective effects in PD models include guaraná (against rotenone in SH-SY5Y cells), Antarctic krill oil (improved locomotor activity and dopaminergic neurons in zebrafish), lutein (dose-dependently improved cognitive and motor outcomes in rats), cytochalasin compounds from endophytic fungi (against MPP+), Erythrina velutina extract, rizonic acid, and xyloketal derivatives (against 6-OHDA or ROS-mediated damage), sodium butyrate (an HDAC inhibitor that epigenetically restored dopamine transporter and VMAT2 expression against rotenone and MPP+), allopregnanolone (promoted TH-positive cell regeneration via BDNF and CaMKIIδ3 against 6-OHDA), wedelolactone (upregulated the neuroprotective PD protein DJ-1/PARK7), dexmedetomidine (neuroprotective via ERK1/2-mediated histone acetylation), along with 7,8-dihydroxyflavone, cordycepin (against rotenone in PC12 cells), AMG9810 (a TRPV1 antagonist that reduced motor deficits but impaired cognition with chronic use), insulin with TLR4 inhibitor TAK242 (improved motor performance and normalized α-synuclein in 6-OHDA rats), catalpol (reduced α-synuclein and improved mitochondrial function against rotenone), genistein, Taohe Siwu decoction, Ligusticum chuanxiong compounds, and Nigella sativa fatty acids.

Since paraquat and other herbicides are among the strongest environmental risk factors for Parkinson’s, it is also noteworthy that DMSO has been shown across multiple studies to scavenge the hydroxyl radicals generated by paraquat,^1,2,3,4 including direct evidence from rats of DMSO intercepting paraquat-generated hydroxyl radicals via Fenton-like chemistry, and in bacterial biosensor assays, DMSO scavenging up to 96% of the superoxide radicals generated by paraquat. DMSO has also been shown to be directly neuroprotective against paraquat in cultured striatal cells, suppress paraquat-induced inflammatory signaling (e.g., IL-8 and neutrophil chemotactic activity), and protect DNA from paraquat-induced mutagenesis — providing a potential mechanistic explanation for the epidemiological finding that DMSO exposure is inversely associated with Parkinson’s risk. Additionally, myrtenol, andrographolide (via Nrf2/HO-1), VPA (an HDAC inhibitor), chymostatin, propofol and resveratrol each combined with DMSO to counteract paraquat-induced toxicity and oxidative stress across various tissue models.

Note: α-synuclein aggregation into toxic fibrils is a core driver of Parkinson’s neurodegeneration. One study found DMSO at 0.75-1.0%, especially when combined with ferric iron, promoted α-synuclein oligomer formation and cytotoxicity. However, when oral DMSO was tested in living mice (both normal and transgenic mice overexpressing human α-synuclein), no increase in α-synuclein aggregation, no neuronal loss, and no Parkinson’s-like pathology was detected. Likewise, DMSO injected directly into the substantia nigra has not been found to cause dopaminergic neuron loss, ubiquitinated protein accumulation, or behavioral deficits^1,2 — suggesting that whatever pro-aggregant effect DMSO has on α-synuclein in isolated cell cultures (at much high concentrations than it can reach clinically) does not translate to the living body.

In addition to the experimental evidence, I have received a few reports from readers and physicians who had success with DMSO. As my experience is primarily with IV DMSO (which I believes offers the greatest benefit), I wanted to share this entire sample that includes non-IV approaches to illustrate to difference between them.

One wife described what happened when her husband with Parkinson’s received an IV drip of mannitol and DMSO during stem cell therapy in Amsterdam: “He bounced down a flight of stairs without using the handrails, cut his own food for a week after, spoke clearly, opened cab doors.” They knew it wasn’t the stem cells, which would take months to show results.

The most detailed report came from a research scientist diagnosed with PD in 2018, who had already controlled his non-motor symptoms with sulforaphane (an Nrf2 activator) but still had the full range of motor symptoms. After systematically testing oral DMSO over several months, he found that at an optimal dose of 1.2–1.5 g/day, bradykinesia was eliminated, pain and dystonia reduced by 80%, stiffness reduced by 50%, and energy levels were markedly higher. He observed that DMSO addressed motor symptoms where sulforaphane had not, suggesting DMSO was reaching the brain in ways sulforaphane could not — consistent with DMSO’s known ability to cross the blood-brain barrier. Notably, doses above 1.5 g/day reliably worsened tremor, stiffness, and sleep, but these effects fully reversed within two days of stopping.

A third reported that topical and oral DMSO initially helped her husband with Parkinson’s walk short distances, but the effect did not persist.

Additionally, I have also received a few reports of oral DMSO helping readers with Parkinson’s, but as they were in passing (verbally) I can’t offer any specifics on them.

Given all of this, I believe DMSO is quite helpful for Parkinson’s disease — oral administration is likely to benefit patients, IV significantly more so — and that the best results will ultimately come from combining DMSO with a complementary neurotrophic agent. Currently, I have identified one very promising candidate for this purpose (along with a few other possibilities), but as the combination studies above demonstrate, there are likely many more waiting to be discovered.

Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease in which the motor neurons that control voluntary movement gradually die, leading to increasing muscle weakness, paralysis, and typically death within 2–5 years of diagnosis. No cure exists, and the two FDA-approved drugs provide only modest survival benefits. However, as Todd’s story shows, there is hope for ALS, and there is also some research to corroborate it:

• In ALS model mice, long-term oral administration of 5% DMSO significantly increased mean survival time, reduced neurological scores, and improved motor performance (with the improvements being primarily functional rather than histological).^1,2

• Low concentrations of DMSO were found to stabilize SOD1 protein conformation (SOD1 misfolding is a central cause of ALS). Additionally, 5-fluorouridine and epigallocatechin gallate (which is often combined with DMSO) also stabilized SOD1.

•A variety of agents in combination with DMSO have also shown therapeutic benefit in ALS mice. Chronic intraperitoneal resveratrol delayed disease onset, extended survival, and preserved nearly twice as many motor neurons. A GSK-3β inhibitor delayed disease onset, death and partially preserved lumbar motor neurons. ASK1 inhibitors protected against motor neuron death and reduced glial activation. Rapamycin improved the neuroprotective mitochondrial fission/fusion balance. Lycopene dose-dependently reduced oxidative stress, and reduced motor neuron apoptosis. Notably, carboxyamidotriazole potently inhibited inflammatory cytokines in vitro but did not significantly improve onset or survival compared to the DMSO vehicle control in vivo—potentially suggesting DMSO itself was already providing a comparable benefit.

Note: DMSO has also been combined with riluzole (one of the two ALS drugs) to treat a variety of other neurological conditions including neuropathic pain,^1,2 light-induced retinal degeneration,^1,2 hearing loss (where DMSO alone also significantly protected hearing and preserved cochlear neurons), and status epilepticus—all of which data shows DMSO alone treats. Additionally, DMSO has been used as a solvent to screen large numbers of compounds for use in ALS.

In addition to Todd’s remarkable response to topical and particularly IV DMSO, a few other reports suggest DMSO can benefit ALS and related conditions. One book recounts Stanley Jacob treating an ALS patient with DMSO, producing “instant, overnight and slightly delayed wonders of therapy,” (after which their doctor forbade further treatment).
Note: I suspect this case may have been what first inspired a mentor to try IV DMSO for ALS.

Another reader reported that a colleague gave DMSO to her father with ALS and “was surprised at visible improvement in his condition.” Finally, a reader with cramping fasciculation syndrome (a condition that presents like early ALS but does not progress to it) described being driven to the point of planning suicide by the combination of chronic pain and severe sleep deprivation before discovering that oral DMSO dramatically improved the effectiveness of his other medications, allowing him to sleep through the night, largely eliminating his cramping and nerve pain, and giving him back the ability to hold down a job and watch his children grow up.

Note: our (limited) experience has been that IV DMSO halts the progression of ALS rather than reverses it. However, the stories I’ve received suggest some individuals have a considerably more dramatic response — whether due to inherent responsiveness or higher IV doses. One of my major unresolved questions is whether the post-COVID vaccine “atypical” ALS cases respond differently to DMSO than the pre-vaccine ALS we had previously encountered (which is where all of our experience comes from).

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