Corestem is a biopharmaceutical company that researches and commercializes stem cell technology.

ALS (NeuroNata-R®)

We developed the world’s first stem cell therapeutic product for ALS (Amyotrophic Lateral Sclerosis) name of NEURONATA-R®, received the permission of medicines by KFDS in July 2014 and began commercialized medication to patients in February 2015, for the fifth in the world.

NEURONATA-R® inj. (Autologous BM-MSC) is an autologous bone marrow mesenchymal stem cell (autologous BM-MSC) therapy that acts a neuroprotective effect and relieves progression of a disease through prevention of motor nerve cell, survival extension of motor neurons, releasing nerves inflammatory and immune regulation function.

The mechanism of lenzumestrocel on ALS is considered as an expression of anti-inflammatory factors, neuroprotective factors and immunoregulation. When lenzumestrocel was tested in the mouse ALS model, gene expression of Foxp3 was increased, which is the differentiation-inducing transcription factor of Tregs. In addition to the animal model, in an experiment using peripheral blood cells from healthy persons and ALS patients treated with lenzumestrocel, an increase in Tregs (CD4+, CD25+) was confirmed, along with increased expression of Foxp3 and IL-10. Based on these findings, lenzumestrocel is considered to show recovery effects on the disease by inhibiting the immune response-initiated apoptosis of neurons through secretion of anti-inflammatory factors that in turn induce an increase in the differentiation of Tregs.

As one of efficacy outcomes, the change in the ALSFRS-R® score (monthly decline rate) between the lead-in and follow-up period was significantly reduced in the MSC group in comparison to the control group.

Our most advanced pipeline, NEURONATA-R®, is at the stage of insurance approval of Korea to get a reasonable insurance drug price in Korea for enhancing brand awareness in the global market and others 3 pipelines such as CS20AT04 (Lupus), CS10BR05 (MSA) are at the stage of phase I.

Overview of NEURONATA-R®
Neuro “Nerve” + Nata “Birth”
  • Type

    ETC, Orphan drug

  • Approval

    2014. 07. 30 (MFDS)

  • Generic Name


  • Dosage

    1.0 x 106 cells/ kg of body weight concomitant with riluzole

  • Administration

    Intrathecal administration, two injections with 4 wk interval

  • Effect & Efficacy

    Retardation of ALS progression

  • Characteristics

    White suspension fluid filled inside a transparent colorless plastic syringe

  • Amount

    4.0×107cells / 4mL, pre-filled syringe

  • Storage

    Cold (2~8℃) storage

  • Expiration Date

    48 hours after manufacturing

Mechanisms of Action (MoA)

NEURONATA-R® the mesechymal stem cells from bone marrow, produces anti-inflammatory cytokines dominant for neuroprotective effects on motor neuron.

  • Treatment with MSCs increases population ratio of Th2 and Treg cells by producing anti-inflammatory factors such as IL-4, IL-10 and TGF-β.
  • Treatment with MSCs increases M2 phenotype by suppressing TNF-α and IL-1β.
  • Treatment with MSCs has parancrine effects by secreting neurotropic factors such as BDNF, VEGF anf IGF which have protective effects on motor neuron
  1. 1.

    The mechanism of NeuroNata-R therapy in ALS is 1) Treg cell induction, 2) Th2 cell activation, 3) Increased conversion of M2 population, 4) Increased anti-inflammatory cytokines, 5) Released neurotropic factor including VEGF, NGF, BNDF

  2. 2.

    Effectiveness of bone marrow stem cell was mediated by immune-inflammation modulation by elevating the T-regulatory cell population and converting microglial cells from M1 to M2 phenotype

  3. 3.

    Repeated intrathecal injections of autologous MSC was safe and effective for retarding the progression speed of ALS

Change of ALSFRS-R Score after NEURONATA-R® Treatment (Phase II)
Improvement in Deteriorating Physiological Function
MSC group Control group
The mean changes in the ALSFRS-R
total scores (+4 months)
-1.69 (SD 2.51)
-4.67 (SD 3.25)
Functional stability based on the responder
analysis (+4 months)
19% P=0.0002
Functional stability based on the responder
analysis (+6 months)
22.2% P=0.0019
The mean changes in the ALSFRS-R total scores (+4 months)
MSC group Control group
-1.69 (SD 2.51)
-4.67 (SD 3.25)
Functional stability based on the responder analysis (+4 months)
MSC group Control group
Functional stability based on the responder analysis (+6 months)
MSC group Control group
  • Compare the control group, the MSCs group has significant improvement in retardation in their symptom.
  • In the initial 1 to 4 month period. the regression is reduced by almost 50%, it slow down almost 50%
Overview of Adverse Effects
Result of Phase II: No Serious AEs (Just common AEs of intrathecal injection)
Overview of Serious Adverse Events (SAE), p=0.667
MSC group Control
Infections and infestations (n(%)) 1(3.03) 0(0.00)
Pyelonephritis acute (n(%)) 1(3.03) 0(0.00)
Injury, or procedural complications (n, %) 0(0.00) 2(6.45)
Contusion (n, %) 0(0.00) 1(3.03)
Ankle fracture (n, %) 0(0.00) 1(3.03)
Metabolism and nutrition disorders (n,%) 1(3.03) 0(0.00)
Hyponatremia (n, %) 1(3.03) 0(0.00)
Cardiac disorders (n, %) 0(0.00) 1(3.03)
Cardiac arrest (n(%)) 0(0.00) 1(3.03)
Total (n, %) 2(6.06) 3(9.68)
Infections and infestations (n(%))
MSC group 1(3.03)
Control 0(0.00)
Pyelonephritis acute (n(%))
MSC group 1(3.03)
Control 0(0.00)
Injury, or procedural complications (n, %)
MSC group 1(3.03)
Control 2(6.45)
Contusion (n, %)
MSC group 0(0.00)
Control 1(3.23)
Ankle fracture (n, %)
MSC group 0(0.00)
Control 1(3.23)
Metabolism and nutrition disorders (n,%)
MSC group 1(3.03)
Control 0(0.00)
Hyponatremia (n, %)
MSC group 1(3.03)
Control 0(0.00)
Cardiac disorders (n, %)
MSC group 0(0.00)
Control 1(3.03)
Total (n, %)
MSC group 2(6.06)
Control 3(9.68)
  • No significant difference in serious AE (p=0.383)
  • No significant difference in serious ADR (p=0.238)
  • No significant differences in laboratory abnormalities
Manufacturing & Administration Procedure