Stemirac®: A Promising Stem Cell Therapy for Spinal Cord Injury

Estimated reading time: 7 minutes

Traumatic spinal cord injury (TSCI) is a devastating condition that can cause paralysis, sensory loss, and other serious complications. One new treatment option for TSCI is Stemirac. Stemirac is an autologous mesenchymal stem cell (MSC) therapy, conditionally approved by PMDA, Japan. Stemirac stem cell therapy presents hope for TSCI patients to improve their quality of life. 

What is a traumatic spinal cord injury?

TSCI is damage to the spinal cord caused by an external force, such as a car accident, fall, or gunshot wound. SCIs can cause a wide range of clinical symptoms depending on the location and severity of the injury. TSCI can cause either temporary or permanent disability. 

How Common is Spinal Cord Injury?

The most common causes of TSCI are traffic accidents, falls, and sports injuries.

According to epidemiological data, 40-50% of TSCIs are due to traffic accidents. Young adults are particularly vulnerable to TSCs caused by high-speed, high-impact sports such as diving, parachuting, and mountain climbing. Falls are the most common cause of TSCs in older age groups.

The World Health Organization (WHO) estimates that the incidence rate of SCI is 250,000 to 500,000 cases yearly. The prevalence of TSCI is also increasing, with an estimated 2.5 to 5 million people living with TSCI globally.

What are the symptoms and effects of a traumatic spinal cord injury?

The symptoms of SCI vary depending on the location and severity of the injury, which is determined by the American Spinal Injury Association (ASIA) impairment scale.

Paralysis: SCIs can cause paralysis of the muscles below the level of the injury. Paralysis can lead to loss of function in the arms, legs, torso, and bladder.

Sensory loss: SCIs can also cause loss of sensation below the level of the injury. This can affect the ability to feel pain, heat, cold, and touch.

Bladder and bowel problems: SCIs can damage the nerves that control the bladder and bowels, leading to incontinence.

Pain: SCIs can cause pain in the back, neck, and other body parts.

Other symptoms: Other symptoms of SCI may include spasticity, muscle spasms, difficulty breathing, and sexual dysfunction.

Management of Traumatic Spinal Cord Injury

Traumatic spinal cord injury (TSCI) management has improved significantly in recent years, increasing survival rates and life expectancy. However, there is still a need for better treatments to address complications such as pain, spasticity, and bladder and bowel dysfunction.

The World Health Organization (WHO) recommends a comprehensive approach to the management of TSCI, including:

Acute care: This includes stabilizing the patient and managing any life-threatening injuries. It is also essential to prevent secondary injury to the spinal cord by immobilizing the spine and reducing inflammation.

Rehabilitation: This lifelong process aims to help people with TSCI regain as much function as possible and improve their quality of life. Rehabilitation typically includes physical, occupational, speech, and psychological counseling.

Support services: People with TSCI may need access to various support services, such as vocational rehabilitation, financial assistance, and transportation assistance.

The WHO also recommends that people with TSCI have access to trained healthcare providers to manage TSCI.

Availability of regenerative drugs in traumatic SCI

There is growing interest in developing regenerative medicines to target the various pathophysiological processes involved in TSCI.

One such regenerative medicine is Stemirac® stem cell therapy from NIPRO CORP, Japan.

Stemirac® stem cell therapy for spinal cord injury

Stemirac is a Human (autologous) bone marrow-derived mesenchymal stem cells. Stemirac is classified as a Human-derived somatic stem cell product.

It is developed by NIPRO CORP., a Japanese company.

How stemirac stem cell therapy works ?

Stemirac® stem cells can travel to the site of injury and transform into new nerve cells, effectively replacing those damaged or destroyed due to the injury. The following evidence supports this process:

• Patient-derived MSCs express receptors for chemokines and growth factors (EGFR, HGFR, NGFR, and Tie2), adhesion factors (ITGA4 and ITGB1), and invasion-associated factors (MMP1, MMP2, TIMP1 and TIMP2).
• Patient-derived MSCs have the potential to differentiate into nerve cells.

Stemirac® stem cells also secrete neurotrophic factors. These proteins encourage the growth and survival of nerve cells, fostering a conducive environment for nerve cell regeneration. This is substantiated by:

• Patient-derived MSCs express and secrete neurotrophic factors such as NGF and other humoral factors like VEGF and HGF.

Stemirac® stem cells derived from patients exhibit immunomodulatory activity. This is demonstrated by:

• MSCs secrete immunomodulatory molecules TSG-6 and CX3CL1. These molecules are believed to modulate macrophage polarization.

Furthermore, MSCs improve motor function as indicated by the BBB score and increase in neurotrophic factor BDNF secretion in a rat SCI model. They also enhance nerve conduction velocity in a rat model of demyelination. These findings form part of the reference data submitted to PMDA.

Stemirac® stem cell therapy early phase clinical trial outcome

Early-phase clinical trials conducted with 13 patients having traumatic spinal cord injury (TSCI).

Dosage and administration

Autologous cultured MSCs administered 2.0 × 10⁸ cells/body (maximum dose, 3.34 × 10⁶ cells/kg) as a single dose over 30 minutes.

The primary efficacy endpoint was the percentage of patients who improved their AIS grade by at least 1 grade at 220 (± 14 days after SCI, compared to immediately before treatment (40 ± 14 days after injury)

Safety and efficacy of Stemirac® stem cell therapy for SCI

Key findings:

• Stemirac stem cell therapy causes no severe side effects. 
• 12 out of 13 patients showed neurological improvement six months after the injection, as measured by the American Spinal Injury Association Impairment Scale (ASIA).
• 5 patients initially classified as ASIA A improved to ASIA B or ASIA C.
• 2 ASIA B grade patients improved to ASIA C or ASIA D.
• 5 ASIA C grade patients improved to ASIA D.
• Functional improvements observed.

Stemirac® PMDA approval

Stemirac® stem cell therapy conditionally approved by the Japanese PMDA in November 2018.

It is used for eligible SCI patients under specialist supervision.

The approval is valid for 7 years, during which the manufacturer must conduct a post-marketing evaluation of all patients treated with the product.

Ongoing clinical trials with Stemirac® stem cells

The tabulated clinical trial details

Trial ID	jRCT2053210130
Study type and design	Interventional, open, non-randomized controlled trial
Inclusion criteria	Patients using autologous bone marrow derived mesenchymal stem cells Patient should be receiving stem cells for the first time for traumatic spinal cord injury
Dosage and Administration	The product is administered by intravenously Dosage: 0.5 × 108 to 2.0 × 108 MSCs Maximum dosage 3.34 × 106 cells per kg body weight Stem cell solution to be diluted ≥3-fold with physiological saline.
Indication or Performance	TSCI assessed as American Spinal Injury Association Impairment Scale (AIS) grade A, B, or C
Primary outcome	Cohort 1: Percentage of the case with 2 or more levels of AIS improvement from 6-8 weeks (49 +/- 7 days) to 180 days +/- 30 days after injury in AIS A patients aged 20 to 70 years with traumatic cervical spinal cord injury   Cohort 2: Percentage of the case with 1 or more levels of AIS improvement from 6-8 weeks (49 +/- 7 days) to 180 days +/- 30 days after injury in AIS B or C patients aged 20 to 70 years with traumatic cervical spinal cord injury

Click the reference link

Author opinion

The initial conditional and time-limited approval of Stemirac® by the PMDA of Japan has sparked debate, with some expressing concerns about the limited clinical evidence supporting its use. However, authorities have defended the approval of Stemirac®, saying that the benefits for traumatic SCI patients outweigh the risks.

There are several promising mechanisms established in vitro and in vivo. However, MSCs have limited and varied results in clinical trials. Few clinical studies show significant improvements in somatosensory evoked potential, neuropathic pain, motor evoked potential, nerve conduction velocity, bladder function, and/or ASIA impairment scale score. In contrast, others have shown no significant improvement.

However, it is essential to consider the following:

• SCI is a complex and multifactorial condition that involves major biological cascades of acute inflammation, ischemia, and apoptosis of neuronal cells.
• Soon after the initial injury, a complex secondary injury occurs, involving prolonged inflammation, glial scar formation, poor endogenous remyelination, and axonal regrowth.
• Functional recovery is difficult in the presence of glial or fibrotic scar.  
• The key requirements for functional recovery are preventing neuronal cell death, repair, remyelination, and axon regeneration. 

Given the complexity of SCI and the limited treatment options currently available, any improvement in neurological function, even if it is just one ASIA grade, can significantly impact a patient’s quality of life. Reduced social consequences, economic burden, and improved quality of life are all important outcomes for patients with SCI.

Conclusion

Stemirac® an autologous stem cells is a promising new treatment for traumatic spinal cord injury (TSCI). Early-phase human studies have shown that Stemirac® is safe, well-tolerated, and can improve neurological function in TSCI patients. Ongoing clinical trials are expected to confirm Stemirac® long-term safety and efficacy.

Stemirac® offers a new ray of hope for patients with SCI who currently have few treatment options. If Stemirac® is proven safe and effective, it could revolutionize the treatment of SCI and help patients regain their lost function.

References

WHO Fact sheets – Spinal cord injury

Stemirac for injection by Nipro Corporation. PMDA review report

The Roadmap to Approval under Japan’s Two-Track Regulatory System: Comparing Six Regenerative Medical Products

Intravenous infusion of auto serum-expanded autologous mesenchymal stem cells in spinal cord injury patients: 13 case series.

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