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Origin

The starting point of this project can be traced back to the family of an MPS II patient that one of our team members came in contact with online. Our team member learned about the patient's situation after an in-depth conversation with him and told us about the plight of the patient and his family, which made us realize that such a disease still exists in the world. So, we started to try to communicate with more patients, doctors and rare disease organizations, wanting to make some contributions to MPS Type II patients and their families.

Background

According to the information we obtained, MPS type II is a rare X-linked recessive genetic disorder with an incidence of 1/100,000 to 1/150,000. It is caused by a genetic mutation that leads to a deficiency of Iduronate-2-sulfatase (IDS), which catalyzes the degradation of glycosaminoglycans. This deficiency results in the accumulation of large amounts of glycosaminoglycans in tissues and organs, leading to pathological changes in multiple organs and systems of the bod ^[1].

Based on the severity of the disease, it can be classified into severe and mild types, in which the central nervous system is affected in the severe form and patients usually die within 20 years of age.

Through interviews with doctors and patients' families, we learned that due to the rarity of MPS type II, patients often have to go through a very complicated route to seek medical treatment before they can be diagnosed. And there is no effective curative treatment after diagnosis, and the main treatments used in clinical practice are enzyme replacement therapy, hematopoietic stem cell transplantation, and symptomatic treatment ^[2] .

Problem

An in-depth look at the available treatments revealed deeper difficulties faced by MPS type II patients and their families. The first problem is that the treatments available to patients are limited and variable in their effectiveness. Symptomatic treatment was used in about 50% of the patients treated, and there was no significant difference in their satisfaction with the treatments compared to dissatisfaction; enzyme replacement therapy was used in about 40% of the patients, and there was a significant difference in their satisfaction with the treatments compared to dissatisfaction; and hematopoietic stem cell transplantation was used in about 30% of the patients, and there was no significant difference in their satisfaction with the treatments compared to dissatisfaction. Among them, the main problem of symptomatic treatment was the lack of significant therapeutic effect. As for enzyme replacement therapy and hematopoietic stem cell transplantation therapy, they share a common problem - high cost of treatment, which is another problem that most of the patients' families are facing, as we learned. In the case of enzyme replacement therapy, the average cost of medication is 29,900 RMB; in the case of hematopoietic stem cell transplantation, the average medical cost is around 400,000 RMB. In addition to the direct medical costs, the patient's family also has to bear the non-direct medical costs, such as accommodations, transportation, and nutritional supplements. Both of these problems impose great mental and physical burdens on patients and their families. ^[3]

Project Introduction

Our project aims to provide an innovative therapeutic strategy that is both more efficient and economically viable, thereby alleviating the suffering of patients and the financial burden on their families. Exosomes are lipid bilayer nanoparticles typically ranging from 30 to 100 nanometers in diameter. They originate from the endosomal pathway and are secreted into the surrounding extracellular space through exocytosis. Exosomes possess a unique ability to transmit information between cells, which can influence the function of recipient cells. In recent years, exosomes have shown great potential as drug delivery vehicles, particularly engineered exosomes, which are widely used in disease treatment due to their low immunogenicity and targeting capabilities.

Based on this background, our project has set clear goals: to construct engineered exosomes that carry IDS enzymes to reduce the accumulation of GAGs in the tissues of MPS II patients, thereby alleviating their suffering. Currently, our project has progressed to the third generation, with high expression of IDS in the third-generation exosomes, and their efficiency in crossing the blood-brain barrier in vitro has significantly improved compared to the second generation. Our team will continue to uphold our original intention and responsibly address global health issues, further refining our project. We envision a future where, with the continuous emergence of more advanced treatment methods, the health of children will be more effectively safeguarded.

Significance

Therapeutic molecules delivered through exosomes can maintain a high concentration in target tissues, enhancing therapeutic efficacy. The natural membrane structure of exosomes effectively protects the therapeutic molecules inside, reducing their degradation in the body, thereby improving treatment stability and longevity. Exosomes have high biocompatibility, and compared to traditional drug delivery systems, they may reduce damage to healthy cells and minimize drug side effects. Additionally, exosomes can better traverse the blood-brain barrier, which is particularly important for treating MPS II type, a condition involving the nervous system.

Through exosome delivery systems, personalized treatment plans can be developed based on the specific needs and disease characteristics of different patients. This approach helps to more accurately address specific enzyme deficiencies within patients.

Utilizing exosomes to treat MPS II type holds great potential to enhance targeting, effectiveness, and reduce side effects. With ongoing research and technological advancements, exosomes may become an important therapeutic strategy, bringing new hope to patients with MPS II type.