December 3, 2021 is a milestone day for domestic rare disease patients, especially SMA (Spinal Muscular Atrophy) patients and their families. The adjustment results of the 2021 National Medical Insurance Drug List were released on the same day, and 7 new drugs for rare diseases were added, including the once "700,000 injections" of Nosinagen Sodium Injection (English brand name Spinraza®), which means that in recent years The inclusion of high-value rare disease drugs called for by many parties into medical insurance has achieved a zero breakthrough.
"Since January this year, the injection patients have been 'blowout', and previously untreated SMA patients have emerged in large numbers." Mao Shanshan, the leader of SMA-MDT) and also the leader of the SMA diagnosis and treatment expert group in Zhejiang Province, said in an interview with The Paper (www.thepaper.cn) that as of the end of last year, his team had diagnosed and managed a total of 17 cases. The latest number of SMA patients treated with spinaxine sodium is 72.
SMA patients receiving Nosinagen sodium need to complete 4 injections in the first 2 months, and Mao Shanshan described the past few months as "densely arranged". However, in addition to being busy, what makes her even more emotional is, "For patients, they have hope of rebirth, and urgently need to find a doctor to use the medicine, but this is also not easy for us doctors. thing."

Mao Shanshan, chief physician of the Department of Neurology, Children's Hospital Affiliated to Zhejiang University School of Medicine, is treating a pair of twins with SMA.

As a rare disease with high "well-known" in China, SMA has entered the era of disease-modifying treatment from no cure. In this new context, there are many new challenges that Mao Shanshan and other doctors need to face, and the most urgent one is: how to improve the diagnosis and treatment rate of SMA and shorten the patient journey from the patient side?
Obviously, improving the diagnosis and treatment rate is the premise that medical treatment can benefit more patients in the era of disease-modifying treatment. In fact, this is also a long-standing pain point in the field of rare diseases.
Professor Huang Shangzhi, a well-known medical genetics expert in China and a genetics researcher at the Institute of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, previously stated on this issue that the identification, diagnosis and intervention of rare diseases should be regarded as "a scientific development". The problem". He emphasized, "Even medical staff's awareness of rare diseases is gradually improving, and the awareness of different institutions and different personnel is gradually improving."
From doctors, to patients, and even to society as a whole, how to increase awareness of SMA? Mao Shanshan has been thinking about this issue for a long time. Starting from this question, in April 2021, Mao Shanshan and Lin Wei, assistant to the dean of the School of Media and International Culture, Zhejiang University, and director of the Department of Film and Television Art and New Media, Zhejiang University, cooperated with the special project of interdisciplinary pre-research of Zhejiang University "'due to rare The information coping and management strategy of “Returning to Poverty”—Taking Spinal Muscular Atrophy (SMA) as an Example” came into being.
"A large part of the delay in diagnosis of SMA patients is due to insufficient media literacy. Patients do not know what disease they have, and even professional doctors may not have seen the disease. There is a huge common message between doctors and patients. Lack of." At the online press conference of the "White Paper on Health Information Literacy of Chinese SMA Patients" (hereinafter referred to as "White Paper") held on the evening of May 31, Lin Wei said that SMA patients and their families need to go to the society, and the society also Need to move towards SMA. The "White Paper" project is based on the above-mentioned topics.
"Sky-high-priced drugs" are included in medical insurance, and the era of SMA disease-modifying treatment begins
Rare diseases are a huge challenge globally. From the point of view of the disease itself, it is also one of the biggest medical challenges facing human beings, of which 80% of rare diseases are inherited diseases.
SMA is an autosomal recessive disorder caused by mutations in the survival motor neuron 1 (SMN1) gene, resulting in progressive, symmetrical muscle weakness and Muscular atrophy ranks first among lethal genetic diseases in children under 2 years of age.
The age of onset varies greatly, and the disease can occur from before birth to adulthood, and most of the onset is in children. According to the patient's age at onset and the highest motor function that can be achieved, it can be divided into 0, I, II, III and IV types. Data show that among the most common types I, II, and III patients in childhood, 80% of type I patients die within 1 year of age, and rarely live beyond 2 years of age; type II patients are often accompanied by severe bone digestion and nutrition, etc. System damage; although type III can walk in the early stage, as the disease progresses, the motor function will gradually decline, and even the ability to walk will be lost.

SMA disease classification.

The incidence of this rare disease in surviving neonates in European and American populations is about 1/10,000, and the carrier frequency is 1/40-1/50. It is worth mentioning that there is currently no exact data on the incidence in China, and the carrier frequency in the Chinese population is about 1/42.
Hope for patients started in 2016. Mao Shanshan mentioned that 20 years after the causative gene was discovered, the first disease-modifying therapy (DMT) drug for SMA was approved. The so-called DMT refers to the treatment or intervention that has a beneficial outcome in the course of the disease by affecting the pathophysiological process of the disease. In December of that year, Nosinagen Sodium Injection was approved in the United States.
The first year of the "drug treatment era" for Chinese SMA patients is 2019. In February of that year, Nosinagen Sodium Injection was officially approved by the State Food and Drug Administration, becoming the first drug for the treatment of SMA in China. Up to now, there are two drugs approved for the treatment of SMA in China. In addition to Nosinagen Sodium Injection, in June 2021, the State Food and Drug Administration approved the Class 1 innovative drug Risprolan Oral Solution Powder (Chinese trade name: Aiman) declared by Roche Pharmaceuticals through the priority review and approval process. Xin®, English trade name: Evrysdi®) is listed for the treatment of SMA in patients aged 2 months and above. Rispolam is currently approved in the United States for the treatment of children and adults with SMA of all ages.
In a 90-minute "soul negotiation" last year, Zhang Jinni, a negotiator of the National Medical Insurance Administration, and others benefited more SMA patients with the once "high-priced drug".
In Mao Shanshan's view, the availability of medicines is an important factor that has greatly increased the attention of SMA. "After Noxinagen Sodium entered the medical insurance, the medicines were suddenly much cheaper, which aroused national attention. It spread to the whole society at once. It was not recognized before, mainly because there was no effective treatment plan, and many grassroots doctors did not recognize this disease."
In just 5 months since the beginning of this year, there have been 55 new SMA patients treated by the Mao Shanshan team who received Nosinagen sodium treatment. In the previous 2.5 years, only 17 patients had been treated with Nosinagen sodium.
As more SMA patients try treatment, Mao Shanshan emphasized that we should pay attention to the improvement of the quality of life of these patients, and the improvement of the quality of life cannot be solved by drug treatment alone. "While drug treatment, combined with multidisciplinary management, including care throughout the life cycle, these are very important, and we must continue to bring them confidence and love."

On January 1, 2022, SMA patient Xinxin completed the injection, and the team of Mao Shanshan from the Children's Hospital Affiliated to Zhejiang University School of Medicine presented the Little Warrior Gold Medal. The surging news reporter He Liping

For example, Mao Shanshan mentioned that among the patients receiving Nosinagen sodium treatment, the most difficult injections are currently obese and scoliosis patients. Typically, before the injection, the doctor completes local anesthesia and then injects the patient with SMA through a lumbar puncture. Different degrees of obesity and scoliosis can cause corresponding difficulties in lumbar puncture.
"After the patient takes the medicine, is the skeletal sitting position corrected with braces; if the child is too fat, we will tell him that you need to be thinner next time; or if you eat too little, we will try to improve the patient's health. Appetite, and also help them to improve their swallowing function." Mao Shanshan said that for things other than injections, the team needs to "focus" on patients and families, "only in this way can these children and their families be truly improved. quality of life.”
Mao Shanshan emphasized to the surging journalists when Noxinagen Sodium Injection was included in the medical insurance before, "What we have to do at this time is to build a better MDT (multidisciplinary diagnosis and treatment) team, so as to provide more and more opportunities in the future. SMA patients who can use many medicines provide the most comprehensive and accurate individualized medical resources." The so-called MDT is the discussion of cases of a certain disease or a systemic disease by multidisciplinary experts, based on the comprehensive opinions of various disciplines. A treatment model that develops the best treatment plan for a patient, and is often used in the diagnosis and treatment of complex diseases.
The society lacks awareness of SMA, opening up the "last 10 kilometers" of information dissemination?
The era of disease-modifying treatment has begun. However, according to Mao Shanshan and Lin Wei, there is still a lot of work that needs to be improved for SMA. What is imminent is how to bring more patients to the doctor who can identify and diagnose SMA in the shortest possible time?
Many of the patients in Mao Shanshan's case database have a late "diagnosis certificate". She mentioned a pair of patients who made her extremely distressed, a 13-year-old boy Xiaoyu (pseudonym), who was diagnosed with SMA-II in March 2018, after 9 years. Xiaoyu's sister, 8 years old, was diagnosed with SMA-III type in March 2016, after 2 years.
"After my sister was diagnosed, he was finally diagnosed, and he took a lot of detours. Because he couldn't walk, he was diagnosed with cerebral palsy at first, and then underwent intracranial cystectomy, thinking it would solve the problem, but he still has not been able to walk independently. "Mao Shanshan mentioned that it is not uncommon for a family to have two children with SMA. If such a family has received correct genetic counseling, there will be no more children born with SMA.
Mao Shanshan mentioned that the long-term diagnosis process and the long-term lack of standardized management will have an immeasurable impact on patients. "We are facing 11 cases of SMA patients with scoliosis of more than 50 degrees this year, and Xiaoyu belongs to more than 80 degrees. Severe scoliosis with a twisted S shape."

Drizzle's spine full-length film.

On March 23 this year, Xiaoyu completed the difficult "ultrasound-guided intrathecal drug treatment of scoliosis" by the SMA-MDT expert team of Zhejiang University Children's Hospital. Ten years of hope come to an end. "Although it is the most difficult, we have still given him all 4 injections so far." said Huang Jinjin, deputy director of the anesthesiology department of the operating doctor.
"I have encountered rare disease patients in the past few years. Very few patients can be diagnosed within a month, and some even take 10 years. Why is this?" Such questions have always plagued Mao Shanshan, she and Lin Wei, etc. People focused the solution on improving the health information literacy of SMA patients and their families.
In 2003, the American Medical Libraries Association (MLA) pointed out that information ability should be introduced into health literacy research, and information literacy and health literacy should be integrated, and then the concept of health information literacy (HIL) was proposed for the first time. Information and services, the ability to make sound judgments and decisions to maintain and promote one's own health.
It is mentioned in the "White Paper" that the research on health information literacy in my country is relatively late and is still in its infancy. However, existing studies have mainly focused on common chronic diseases such as diabetes and hypertension, and the health information literacy survey of patients with rare diseases has not yet been carried out.
Chen Ziliu, Executive Director of Market Insights at AiKunwei, said at the press conference that through previous research, it can be found that "health information literacy reflects people's ability to manage health to a certain extent, and its improvement can improve the treatment effect of patients to a certain extent. and quality of life.”
In order to conduct a comprehensive survey on the health information literacy of SMA patients/family members, the Children's Hospital Affiliated to Zhejiang University School of Medicine, Zhejiang University School of Media and International Culture, Meier SMA Care Center and IQVIA Ai Kunwei jointly launched the "White Paper" project. Chen Ziliu said that this survey on the health information literacy of SMA patients is the first among rare diseases in the country.
The study found that people with SMA took an average of 10.8 months from onset of symptoms to diagnosis. Before the diagnosis, the health information literacy of patients/family members was the lowest, and with the passage of the medical treatment journey, the health information literacy of the respondents showed a clear upward trend. However, in general, the overall level of health information literacy of SMA patients/family members in my country is still low. Among them, health information awareness and health information application ability are relatively strong, while health information query and evaluation ability is weak.
Lin Wei said that opening up SMA information dissemination is not to solve the problem of the last 1 kilometer, "but a full 10 kilometers away."
How to get through? The White Paper makes the following recommendations for improving health information literacy among patients with SMA:
First, government, industry, academia, and research jointly build “two banks and one mechanism” for SMA-specific diseases to improve the visibility and standardization of SMA information. The project team calls on the government to take the lead, related academic associations, medical institutions, doctors, enterprises and patient organizations to participate in the establishment of the "two banks and one mechanism" for SMA diseases under the framework of the "two banks and one mechanism" for national health science, and establish National and provincial SMA popular science expert database, as well as national SMA popular science resource database, on this basis, build an all-media SMA popular science knowledge release and dissemination mechanism, create a fair, just, authoritative and standardized SMA information platform, provide patients with diseases including diseases , medical treatment, medication, rehabilitation and other information one-stop solution.
Make full use of the characteristics of search engine as the "first contact" or even "single channel" for information query of SMA patients at the beginning of symptoms, led by the search engine, and take the SMA "two databases" as a fair, impartial and professional content source , to build a search engine-based SMA information aggregation platform to further enhance the visibility of SMA-related information in search engines, and provide patients with clear, rich, and accessible information guidance.
Second, use the SMA content crowdfunding mechanism to expand the quantity, improve the quality, and reduce the barriers to patient information. The project team believes that high-quality, rich and diversified SMA popularization content cannot be separated from the participation and co-construction of grassroots doctors, SMA patients and family members.
Therefore, it is recommended to start from the production mechanism and transition from one-way communication based on institutions (academics/associations, hospitals, enterprises and patient organizations, etc.) to those based on institutions and individuals (primary doctors, patients/family members, medical students and other individuals) Crowdfunding and dissemination, with the help of the power of the group, expand the SMA popular science content library, and further reproduce the single-form text popular science in the form of short video, audio, comics, etc. that are more intuitive, interesting, and easier to spread, so as to adapt to different types new media carrier. For the quality control of crowdfunding content, it is recommended to establish a training mechanism for SMA popular science content, and the content will be released after being reviewed by the institution.

Schematic diagram of the SMA content crowdfunding mechanism.

Third, encourage more medical personnel and media workers to participate in public education. The project team pointed out that, as a rare disease, the public visibility of SMA in the Internet information environment has always been low, and the public awareness rate is not high, which is still a long-term reality.
Therefore, the project team calls for more medical staff with knowledge and experience in SMA diagnosis and treatment, and more media interested in improving public health literacy to participate in the SMA popularization work for the public (including the secondary production of SMA information), so as to provide vivid, Interesting and diversified content, publicize the knowledge of SMA prevention and treatment in all media, especially new media channels, share the cutting-edge academic achievements of rare diseases, call on the public to participate in the screening of SMA carriers, take the first hurdle of SMA prevention and treatment, and enhance the public's understanding of SMA. awareness rate.
Mao Shanshan told The Paper about a detail in the past two weeks, "I counted, I have seen 5 SMA-I patients in the past two weeks, and I couldn't see 5 patients in the past 2 years. The reason is that most patients with SMA-I type were previously unknown, and most died within 1 year of age without corrective treatment, and rarely lived past 2 years of age. Respiratory disease left."
The increased "awareness" of SMA is extending the lives and improving the quality of life for some patients. However, it still takes a huge effort from all walks of life to make the families in need get the correct knowledge in a timely manner.