Source of Medicine Intelligence Network: Medicine Intelligence Network

Recently, Shize Biotechnology announced that its self-developed universal iPSC derived subtype neural precursor cell injection product XS-228 injection has been fully approved by the US FDA for registration in clinical trials for the treatment of amyotrophic lateral sclerosis (ALS).

This breakthrough not only marks an innovative breakthrough in the field of cell therapy in China, but also brings new hope to patients with ALS.

One of the 'Four Deadly Diseases of the World'

ALS, as one of the "Four Deadly Diseases of the World", its complexity and harmfulness cannot be ignored.

ALS (amyotrophic lateral sclerosis) is a rare and progressive neurodegenerative disease that primarily affects motor neurons in the brain and spinal cord. These neurons are responsible for controlling muscle movement. As they gradually regress and die, patients may experience symptoms such as muscle weakness, atrophy, and stiffness, ultimately leading to the loss of motor ability, and even the inability to swallow, speak, and breathe. Patients may feel as if they are gradually "frozen", hence the name "ALS".

At present, the etiology of ALS is not fully understood, but research has shown that some patients have a family genetic background, with the most common pathogenic genes being the C9orf72 gene and the copper/zinc superoxide dismutase (SOD1) gene. In addition, age, long-term exposure to toxic substances, smoking, and high-intensity exercise may also be associated with the onset of the disease.

In 2014, the "Ice Bucket Challenge" brought ALS into the public eye and raised social awareness of this rare disease. In addition, public figures like Cai Lei, with their tenacious vitality and spirit, have inspired countless patients and researchers.

In recent years, cell therapy, as an emerging treatment method, has brought new hope for the treatment of ALS. The core idea of cell therapy is to repair or replace damaged nerve cells by transplanting healthy cells. The iPSC derived cell therapy program of Shize Biotechnology is based on this concept, which involves inducing pluripotent stem cells to differentiate into specific neural precursor cells and then transplanting them into the patient's body to achieve repair of the damaged nervous system.

From a technical perspective, the iPSC derived subtype neural precursor cell injection (XS-228 injection) from Shize Biotechnology utilizes advanced cell reprogramming and differentiation techniques. By reprogramming the patient's own somatic cells into pluripotent stem cells and differentiating them into specific neural precursor cells, this therapy is expected to achieve repair and regeneration of the nervous system in patients with ALS. In addition, this "spot type" cell therapy regimen also has the advantages of strong scalability and high cost-effectiveness.

It is worth mentioning that although it has not yet been launched on the market, the XS-228 injection from Shize Biotechnology has already obtained one "China's first" and two "global firsts": China's first iPSC derived cell drug has been certified by the US FDA and granted global orphan drug status, the world's first and only iPSC derived cell drug with orphan drug status for the treatment of ALS, and the world's first and only officially approved regenerative nerve cell therapy product for the treatment of ALS that has been registered for clinical trials in the United States.

The FDA's approval of its clinical trial this time will provide further validation for the safety and efficacy of the therapy. If the experiment is successful, it will be a major breakthrough in the field of treating ALS and is expected to become an important means of treating ALS.

Innovative therapies emerge

It is gratifying that XS-228 injection is not the only one to break the "freeze". In recent years, multiple innovative therapies have emerged in the treatment of amyotrophic lateral sclerosis, bringing new hope to this disease that lacks effective treatment methods.

These innovative therapies cover multiple directions such as ribonucleic acid (RNA) therapy and mesenchymal stem cell (MS) therapy.

Ribonucleic acid (RNA) therapy

Tofersen is an antisense oligonucleotide (ASO) drug that inhibits the production of mutant proteins by targeting the mRNA of the pathogenic gene SOD1. Some ALS patients carry mutations in the SOD1 gene, which lead to the accumulation of toxic proteins and accelerate the death of motor neurons. Tofersen acts directly on the central nervous system through intrathecal injection, blocking the expression of pathogenic genes and delaying disease progression from the root.

Tofersen's Phase III clinical trial showed that for patients with SOD1 mutations, it can significantly reduce the level of neurofibrillary light chain (NfL, a marker of nerve damage) in cerebrospinal fluid and delay motor function decline. In 2024, Bojian Biotechnology announced that Tofersen Injection had been approved for market in China, becoming the first precision therapy for hereditary ALS.

Mesenchymal stem cell (MSC) therapy

Mesenchymal stem cell (MSC) therapy is an emerging cell therapy technology with broad clinical application prospects. MSCs originate from various tissues such as bone marrow, umbilical cord, adipose tissue, etc., and have the ability of self-renewal, multi-directional differentiation, and immune regulation. In recent years, MSC therapy has shown significant potential in the treatment of various diseases, especially in the field of ALS where significant progress has been made.

In 2021, an article titled "Randomized placebo-controlled Phase 3 Study on Inducing High Level Neurotrophic Factor Secretion from Mesenchymal Stem Cells for the Treatment of Amyotrophic Lateral Sclerosis" was published in the international journal "Muscle&Nerve". The study showed that in Phase 3 clinical trials, MSC-NTF cell therapy had good tolerability and no safety issues. Compared with placebo, MSC-NTF participants with milder symptoms retained more function at 28 weeks and significantly improved biomarkers in cerebrospinal fluid. This study provides important evidence for cell therapy of ALS, but larger scale trials are still needed to confirm its efficacy.

conclusion

The universal cell therapy regimen of Shize Biotechnology has been approved by the FDA for clinical use, marking an important step forward in the field of ALS treatment. This innovative therapy not only brings new hope to patients with ALS, but also provides a new direction for the development of cell therapy technology. With the advancement of various innovative therapies for treating ALS, we look forward to bringing substantial benefits to ALS patients as soon as possible.