Amplification of brain self-repair processes translating into persistent functional recovery.

A 3-month course with NeuroAiD:

• Increases by 50% the odds of achieving functional independence at 6 months.¹
• Enhances persistent functional recovery and independence on top of rehabilitation for up to 2 years.^1,2,3
• Improves motor recovery with benefits observed as early as 1 month of treatment and at each time point up to 3 months.⁴

The CHIMES-E Study, functional recovery over 2 years.¹

• Pre-planned study on 880 subjects* with Acute Ischaemic Stroke followed up for 2 years.
• Randomised to 3 months of either NeuroAiD or placebo.

+50% in odds of achieving functional independence at 6 months.

Persistent recovery with benefits observed over 2 years

In subjects with 2 to 4 prognostic factors of poorer outcome** and receiving NeuroAiD² :

• More subjects achieved functional independence over time versus placebo.
• Significant improvements observed as early as 3 months.
• Less subjects deteriorating over time versus placebo, illustrating the persistence of the recovery

*CHIMES-E published in Cerebrovascular Diseases journal is the pre-planned extended follow-up to 24 months of the CHIMES study5, a 3-month study conducted on 1099 subjects. The CHIMES study was published in Stroke journal in 2013. **Prognostic factors are defined as older age, female sex, baseline NIHSS score ≥ 10 and time to first dose 48h.

Combining NeuroAiD and Rehabilitation doubles the odds of achieving functional independence versus Rehabilitation alone.³

• Analysis of 380 subjects having received rehabilitation during 3 months of NeuroAiD (n=200) or placebo (n=180).

+50% in odds of achieving functional independence at 6 months.

Persistent recovery with benefits observed over 2 years

• Statistically significant odds ratio at all time points from 3 months to 2 years from stroke onset.
• Persistent recovery with benefits sustained for up to 2 years, as supported by low Numbers Needed to Treat (NNT) range from 5 to 7 over the 24-month follow-up period.

NeuroAiD improves motor recovery.⁴

• Randomised double-blind study placebo-controlled study in post-acute stroke subjects with upper and lower limbs deficits, included up to one month following an ischaemic stroke (n=150).

Significantly better motor recovery observed since month 1 and sustained up to month 3.

References:

1. Venketasubramanian N, et al. CHInese Medicine NeuroAiD Efficacy on Stroke recovery – Extension Study (CHIMES-E): A multicenter study of long-term efficacy. Cerebrovascular Dis. 2015; 39:309-318.
2. Venketasubramanian N, et al. Prognostic Factors and Pattern of Long-Term Recovery with MLC601 (NeuroAiD™) in the Chinese Medicine NeuroAiD Efficacy on Stroke Recovery – Extension Study. Cerebrovascular Dis. 2017; 43:36–42.
3. Suwanwela NC, et al. Effect of Combined Treatment with MLC601 (NeuroAiDTM) and Rehabilitation on Post-Stroke Recovery: The CHIMES and CHIMES-E Studies. Cerebrovasc Dis. 2018 doi: 10.1159/000492625.
4. Harandi AA, et al. Safety and efficacy of MLC601 in Iranian patients after stroke: a double-blind, placebo-controlled clinical trial. Stroke Research and Treatment. 2011; doi:10.4061/2011/721613.
5. Chen C, et al. Chinese medicine Neuroaid efficacy on stroke recovery – A double-blind, placebo-controlled, randomized study. Stroke. 2013; 44:2093-2100.
6. Theadom A, et al. MLC901 (NeuroAid II™) for cognition after traumatic brain injury: A pilot randomised clinical trial. Eur J Neurol. 2018;25(8):1055-e82.
7. Pakdaman H, et al. MLC901 for moderate to severe traumatic brain injury: pilot, randomised, double-masked, placebo-controlled trial. Open Acc J Comp & Alt Med. 2020; 2(5).OAJCAM.MS.ID.000148. DOI: 10.32474/OAJCAM.2020.02.000148.

By stimulating brain neurorepair processes, NeuroAiD enhances recovery after a TBI

• Improves 2 of the most commonly impacted cognitive domain post-TBI⁶
• Enhances functional outcome to reach independency in moderate and severe TBI⁷

The BRAINS study⁶

• Randomized, placebo-controlled pilot trial on 79 mild to moderate TBI subjects.
• Recruited from 1 month to 12 months from TBI.
• Receiving 6 months of NeuroAiD or matching placebo and followed-up until 9 months.

NeuroAiD significantly improves Executive Functioning and Complex Attention at 6 months.

• Continuous improvement of Executive Functioning, significant at 6 months.
• Executive Functioning deficit is directly impacting activities of daily living and affecting cognitive rehabilitation.

• Continuous improvement of Complex Attention, significant at 6 months.
• Complex Attention is one of the most impacted cognitive domains following a TBI.

Recovering functional outcomes post-TBI⁷

• Randomised, double-blind, placebo-controlled trial in 81 subjects after a moderate to severe TBI.
• Treatment initiated within 24 hours from TBI onset from a 6-month course.
• Dosing schedule: NeuroAiD (MLC901) or placebo at a regimen of 2 capsules, 3 times per day for 6 months.
• Assessment: GOS and modified Rankin Scale (mRS) at month 3 and month 6.

NeuroAiD optimises recovery of moderate and severe TBI subjects over time

• Higher rate of subjects with favourable outcome in NeuroAiD group compared to placebo group at month 3.
• Over 86% of the subjects reached favourable outcome in NeuroAiD group after a 6-month course (including 43.2% with GOS 5).
• Significant differences in favour of NeuroAiD at both time points.

• More subjects reached functional independence (mRS 0-1) in NeuroAiD group vs placebo at month 3 and month 6.
• The proportion of subjects with no symptoms (mRS 0) is superior in NeuroAiD group compared to the placebo group at both time points.
• Significant differences in favour of NeuroAiD at both time points.

Visit the Publicationstab

for more information on NeuroAiD’s clinical data

NeuroAiD has a favourable safety profile and is well-tolerated

The safety profile of NeuroAiD is well established in ischemic stroke patients and TBI patients. Most of the studies made on NeuroAiD were comparative to placebo. There is no better comparator to assess the safety profile of a product.

• No interaction with the standard treatments used in post-stroke management or post-TBI management.^1,3
• No serious side effects associated with NeuroAiD during treatment1. Rare, transient and mild side effects (e.g., gastrointestinal symptoms) were reported1. These are usually resolved by halving the dose for a few days.^3,4
• No serious side effects associated with NeuroAiD during treatment¹. Rare, transient and mild side effects (e.g., gastrointestinal symptoms) were reported¹. These are usually resolved by halving the dose for a few days.
• No increase in delayed adverse events after treatment completion and a follow-up of 2 years.^2,5

NeuroAiD is safe as an add-on treatment for neurological recovery.

To date, no drug interactions with NeuroAiD have been reported. NeuroAiD should be taken in addition to preventive treatments of cardiovascular risk factors commonly prescribed after a stroke; these typically include antiplatelet, antihypertensive, and cholesterol-lowering drugs, among others such as anti-diabetics. Systematic clinical trials have shown that NeuroAiD does not have any interaction with aspirin. Patients taking NeuroAiD with anticoagulants have reported no impact on their INR (International Normalized Ratio). Nevertheless, it is recommended to keep monitoring INR when NeuroAiD is initiated as it is routinely done for patients taking anticoagulants.

Quality Control

NeuroAiD is manufactured in Singapore under the international standards of Good Manufacturing Practice (GMP). The GMP standards are applied to procedures in manufacturing dietary supplements, including approval of raw materials, production and process controls, laboratory testing, and product packaging, labelling, and distribution. These processes are regularly audited by independent health authorities. Every batch of NeuroAiD is analysed thoroughly by third-party independent laboratories to confirm compliance with international standards, ensuring utmost ensuring utmost security of NeuroAiD use.

References:

1. Chen C, et al. Chinese medicine NeuroAiD efficacy on stroke recovery: A double-blind, placebo-controlled, randomized study. Stroke 2013a;44:2093-2100 2. Venketasubramanian N, et al. CHInese medicine NeuroAiD efficacy on stroke recovery – Extension study (CHIMES-E): A multicenter study of long-term efficacy. Cerebrovascular Diseases 2015;39:309-318. 3. Young S, et al. Safety profile of MLC601 (NeuroAiD) in acute ischemic stroke patients: A Singaporean substudy of the Chinese medicine NeuroAiD efficacy on stroke recovery study. Cerebrovascular Diseases 2010;30:1-6. 4. Gan R, et al. Danqi Piantan Jiaonang does not modify haemostasis, haematology, and biochemistry in normal subjects and stroke patients. Cerebrovascular Diseases 2008;25:450-456. 5. Shahripour RB, et al. A Randomized Trial to Assess the Long-Term Safety of NeuroAiD among Caucasian Patients with Acute Ischemic Stroke. Chin J Integr Med 2014;20(11):812-817.

NeuroAiD: Pharmacological Data

NeuroAiD has a multi-target mode of action to boost the main components of endogenous neurorepair and exerts a priming effect on neurorepair by simultaneously activating pharmacological pathways

1. NEURONAL NETWORK PLASTICITY¹²

• Increases survival, neuronal network strengthening and plasticity, and neurogenesis by upregulating Brain-Derived Neurotrophic Factor (BDNF)
• Increases neurite outgrowth and synaptogenesis.
• Promotes a denser axonal and dendritic network.

2. NEUROGENESIS¹²

• Increases the number of newly generated neurons and glial cells.
• Optimizes their migration and differentiation into fully funcitonal cells.

3. ANGIOGENSIS³

• Reduces the leakage of the Brain Blood Barrier and optimizes its repair. Modulates the expression and activity of the mediators involved in neuroinflammation.
• Amplifies the development of micro vessels in the damaged area.

4. NEURO-INFLAMMATION MODULATION⁴

• Reduces the leakage of the Brain Blood Barrier and optimizes its repair.
• Modulates the expression and activity of the mediators involved in neuroinflammation.

NeuroAiD increases Brain Derived Neurotrophic Factor (BDNF) production¹

BDNF is a growth factor which regulates neuronal survival and protects neurons from glutamate-induced damages. BDNF also encourages proliferation and differentiation of new neurons.

In vivo effect of NeuroAiD pre-treatment on BDNF protein levels in cortex sections. (A) Representative epifluorescence microscopy photographs of BDNF immunoexpression in cortical neurons in brain sections. (B) Quantification of BDNF signal intensity in immunostained neurons.

NeuroAiD promotes denser neuronal networks¹

Epifluorescence microscopy confirmed the development of an important axonal and dendritic network on cell cultures with NeuroAiD.

On day 14, in neuronal cell cultures treated with NeuroAiD, epifluorescence showed a remarkable increase of DCX, GAP43 and Synaptotagmin expressions, providing evidence that NeuroAiD triggers:

• Neurogenesis
• Neurite outgrowth
• Synaptogenesis

NeuroAiD promotes both the development of new synaptic connections and the modification of existing ones, including an increase in the number and length of dendrites and synapses. A 60% increase in the length of the neurite was shown at Day 14 for NeuroAiD group.

Effects of MLC601/MLC901 treatment on in vitro Synaptotagmin 1 expression in cultured cortical neurons. Synaptotagmin 1 expression was analyzed after MLC601/MLC901 treatment (1 mg/ml) at Day 7 and 14 of treatment.

NeuroAiD promotes neuroplasticity and neurogenesis to support stroke recovery¹

• NeuroAiD increases proliferation of neuronal progenitor cells by a significant 3-fold effect (p<0.01) in human stem cells.
• NeuroAiD increases the number of mature neurons by a significant 2.1-fold effect (p<0.01) in animal studies.
• Cell cultures treated with NeuroAiD have denser networks of connections with stronger neurons.

Neurogenic effects of MLC901 on human ESC-derived progenitors. (D) Radiant rosette-like aggregates of nestin-positive neural progenitors spontaneously form in low-density cultures. (E) Quantification of the number of rosettes 2 days after the addition of MLC901 (*P < 0.05, **P < 0.01 versus control).

The combination of its selected 9 herbal ingredients has a priming effect on neurorepair to achieve global functional recovery.

• As a priming strategy, NeuroAiD enhances natural neurorepair processes of neurogenesis¹², neuronal network plasticity¹², angiogenesis³ and anti-inflammation⁴.
• These effects add to the consolidation effects provided by rehabilitation to strengthen the newly formed connections and achieve global functional recovery.

Visit the Publications tab for more information on NeuroAiD’s properties and mode of action.

References:

1. Heurteaux C, et al. Neuroprotective and neuroproliferative activities of NeuroAiD (MLC601, MLC901), a Chinese medicine, in vitro and in vivo. Neuropharmacology. 2010;58:987-1001.
2. Quintard H, et al. MLC901, a Traditional Chinese Medicine induces neuroprotective and neuroregenerative benefits after Traumatic Brain Injury in rats. Neuroscience. 2014;277:72-86.
3. Gandin C, et al. MLC901 Favors Angiogenesis and Associated Recovery after Ischemic Stroke in Mice. Cerebrovasc Dis. 2016;42:139–154.
4. Widmann C, et al. The Traditional Chinese Medicine MLC901 inhibits inflammation processes after focal cerebral ischemia. Scientific Reports. 2018;8:18062.