Preface
World boxing champion Ali, literary giant Bakin, math wizard Chen Jingrun, and Deng Xiaoping, the chief architect of reform and opening up, ...... whose fields do not intersect, have been linked by the same disease, Parkinson's disease (PD). Disease (PD).
Parkinson's disease is a common neurodegenerative disease that affects people over 65 years old, with typical symptoms such as tremor, stiffness of the limbs, decreased motor function, abnormal gait, and other symptoms such as constipation, urination difficulties, and abnormal sweating.
According to the World Parkinson's Association, there are currently more than 5.7 million Parkinson's disease patients around the world***, of which the number of people with the disease in China is about 2.7 million, accounting for almost half of the total number of people with the disease worldwide. It is expected that by 2030, China's Parkinson's disease patients will increase to 5 million people, China has become the world's first Parkinson's disease "big country".
(Image source: Medtronic official website)
In the early stages of the disease, drugs are the first choice of treatment, including direct dopamine supplementation, activation of dopamine receptors, blocking dopamine metabolism, increasing dopaminergic, inhibiting acetylcholinergic, and so on. In the later stages, as the disease progresses and drug therapy gradually fails, surgical destruction therapy can be considered, i.e., after microelectrodes are targeted and precisely positioned, radiofrequency needles are used to heat and destroy the diseased cells, which is able to temporarily alleviate the symptoms of PD patients such as limb tremor, stiff joints, and mobility difficulties. The other is now widely recognized as the preferred surgical treatment - Deep Brain Stimulation (DBS), also known as a brain pacemaker.
I. DBS for Parkinson's Disease is highly effective and has unlimited application in the future
Deep Brain Stimulation (DBS) therapy uses stereotactic technology to implant electrodes into certain areas of the deep brain, and then under the control of an Implantable Pulse Generator (IPG) planted under the subcutaneous area below the clavicle bone, the electrodes emit electrical impulses to stimulate the target point to regulate neurological function, ultimately achieving the goal of treating neurological/psychiatric disorders. The IPG, which contains a battery and electronic components to deliver electrical stimulation, can be controlled by the patient and clinician, with stimulation parameters such as frequency, pulse width, and voltage periodically adjusted to maximize the neuromodulatory benefits of DBS.
(Image source: Mayo Clinic website)
History
The origins of DBS therapy can be traced back to the mid-to-late 1800s, when experiments on cortical stimulation in animals laid the groundwork for research on cortical localization; and in the early 1900s, when the first stereotactic frameworks were developed, making it possible to carry out stimulation experiments in deep areas of the brain. The development of the first stereotactic framework in the early 20th century made it possible to conduct stimulation experiments in deep areas of the brain.
The introduction of X-ray pneumoencephalography in 1947 greatly enhanced the targeting ability of surgeons. In the same year, Spiegel and Wycis et al. experimented with electrical stimulation and high-frequency electrocoagulation for Parkinson's disease, and with thalamic electrical stimulation for chronic pain, with later attempts to apply it to the treatment of epilepsy and spasticity.
In the 1950s, the mainstay of treatment for Parkinson's disease was irreversible surgical disfigurement, which is the destruction of the neural tissue that drives Parkinson's symptoms by means of thermal ablation, and included two types of craniectomy and thalamotomy.
The first implantable spinal cord stimulator was developed by Dr. C. Norman Shealy and colleagues in the United States in 1967, an attempt that amounted to the initial conception of the DBS system.
In the late 1960s, some researchers found that levodopa treatment provided significant relief from most Parkinson's symptoms, with the advantages of low risk and low cost. The advent of drug therapy slowed the progress of DBS and stereotactic neurosurgery research.
In the 1980s, many people with Parkinson's disease became resistant to levodopa, and side effects of medication, such as dyskinesia, became apparent. Implantable medical technology improved significantly, and treatment with spinal cord stimulators and pacemakers became routine. 1987, French scholar Prof. Benabid led a team to successfully carry out the world's first implantation of the DBS system, and reported the results of the study of thalamic electrical stimulation for the treatment of tremor in 1991 and 1994, respectively, which opened up the thalamus to electrical stimulation therapy.
In 1997, the U.S. FDA approved Medtronic's application to apply DBS to the treatment of idiopathic tremor and Parkinson's disease.
Today, more than 180,000 patients have received DBS implants worldwide. Although the therapeutic mechanism of DBS is still unknown, the results of studies following implanted cases have shown that DBS is effective in controlling the motor symptoms of Parkinson's disease and reducing drug intake. The success in the treatment of Parkinson's disease has driven the further development of DBS therapy, which is now widely used in the treatment of primary tremor and dystonia, and the U.S. FDA approved the application of DBS for the treatment of primary dystonia, and for the treatment of progressive mental disorders in 2003 and 2009, respectively. Research findings in recent years suggest that DBS will be promising for a variety of disorders, including chronic pain, obsessive-compulsive disorder (OCD) and depression. Additionally, scientists are already experimentally exploring the efficacy and safety of DBS therapy for disorders such as drug addiction, anorexia, obesity, and Alzheimer's disease. With the continued advancement of DBS research, the application space of DBS therapy will be unlimited in the future. Second, foreign giants take the lead in the layout, the domestic enterprises are showing the first
According to the latest research report released by Grand View Research, the market size of DBS in the world in 2016 was about 796 million U.S. dollars, and the compound annual growth rate of the DBS market during the forecast period was 11.5 percent. By 2025, the global DBS market volume is expected to exceed USD 2.1 billion. In the future, thanks to the improvement of living standards and medical technology, the proportion of aging population is increasing, and the incidence of neurological disorders (e.g., Parkinson's, epilepsy, essential tremor, dystonia, etc.), which are prevalent in the elderly population, is gradually showing an upward trend, which further drives the expansion of the DBS market size. In the field of DBS treatment, foreign-funded device giants such as Medtronic, Boston Scientific, and St. Jude (which has been acquired by Abbott) are currently occupying an absolute leading position in the market due to their mature technology and early layout. Domestic companies such as Pinchuk and Jingyu, despite their slightly late start, have been catching up with the market by virtue of superior technology and innovative therapies, and are trying to seize the promising DBS treatment market. (I) Foreign-funded companies
1, Medtronic Activa series - compatible with magnetic **** vibration (MRI) examination of the DBS system
Veteran medical device company Medtronic can be called the originator of the application of DBS therapy. Medtronic was responsible for the development of the first DBS system implanted by Professor Benabid and his team back in 1987, which led to the commercialization of DBS therapy. Since then, the Medtronic DBS system has been approved in the European Union, Canada, and Australia for the treatment of idiopathic tremor, dystonia, and Parkinson's disease, and in 2002, the U.S. FDA approved Medtronic's DBS system for the control and relief of motor symptoms in middle- to late-stage Parkinson's disease, marking the expansion of Medtronic's DBS therapy to Parkinson's disease patients who have been shown to be effective on levodopa, but for whom the drug does not adequately control certain symptoms. Parkinson's disease patients. Notably, this system is also approved for compatibility with magnetic resonance imaging (MRI) under certain conditions, making it the first DBS system on the market to allow patients to undergo MRI after implantation. Currently, Medtronic's Activa Series portfolio consists of three devices: the Activa PC Bilateral Device, the Activa PC Bilateral Device, and the Activa SC Unilateral Device, with the Activa RC being the world's first rechargeable DBS system with a 15-year lifespan.The Activa Series of DBS systems utilize sensory technology and adjustable stimulation algorithms that, while The Activa series of DBS systems use sensory technology and adjustable stimulation algorithms to measure and record electrical signals in key areas of the brain while providing deep brain therapy. In addition, the system's accompanying programmable control system supports real-time programmable settings based on reliable patient data information by physicians on a tablet computer.
In December 2017, the Boston Scientific Vercise product was approved by the U.S. FDA for the treatment of Parkinson's disease. Currently, Boston Scientific's newest Vercise Directional DBS system is available in two products: the rechargeable VerciseGevia and the non-rechargeable, and claimed to be the thinnest and lightest Vercise PC on the market.
Boston Scientific claims that its Vercise Directional DBS system has the latest steering The Vercise Directional DBS System features the latest steering technology, in which a directional lead implanted in a specific region of the brain is attached to eight independently controlled electrodes that deliver precise levels of stimulation to different neurological targets, allowing clinicians to accurately modulate the DBS device in response to changes in the patient's physical needs, including controlling the degree, range, location and direction of electrical stimulation. At the same time, with the program control software with STIMVIEW technology, doctors can visualize the distribution of electrical stimulation in various regions of the brain during DBS treatment, and adjust the treatment plan in a timely manner to ultimately achieve highly personalized Parkinson's treatment goals. 3, Abbott St. Jude Medical InfinityDBS - directional wires to guide the current, wireless platform to facilitate program control
In 2016, Abbott acquired St. Jude Medical for $25 billion, which will St. Jude's heart failure treatment equipment, cardiac catheters, defibrillators and deep brain stimulation device (DBS) businesses together. St. Jude Medical's Infinity DBS system and its directional lead were approved by the FDA in 2016 for the control or relief of Parkinson's disease and idiopathic tremor, the first directional lead approved by the FDA.
The Infinity DBS System realizes the goal of combining innovative segmented directed lead technology with the industry-leading DBS iOS software wireless platform. Among other things, the segmented electrodes on the Directional Leads are able to direct electrical current to desired structural areas of the brain, while allowing physicians to remove current from certain areas that are prone to side effects, thereby maximizing patient outcomes and limiting side effects.
Photo credit: Abbott.com
The system's wireless iOS software platform connects to the DBS implant via Bluetooth, allowing clinicians to personalize the DBS implant in the patient's brain using software on the iPad, and allowing patients to monitor and respond to symptoms and treatments in real time using the digital patient controller on the iPhone. Real-time monitoring and timely feedback. (II) Domestic Enterprises
1. Beijing Pinch Medical's Brain Pacemaker Series - "Industry, Academia, Research and Medicine" Cooperation, Breaking the Foreign Technology Monopoly
Beijing Pinch Medical Equipment Co. ("Punch Medical") was founded in 2008 and is headquartered in Changping Park, Zhongguancun Science Park, Beijing. Its business covers the research, development, production and sales of a series of neuromodulation products, including brain pacemakers, vagus nerve stimulators, spinal cord stimulators and sacral nerve stimulators.
Pinch Medical has established a collaborative innovation model of "industry-academia-research-medicine" by cooperating with Tsinghua University, Beijing Tiantan Hospital, Union Hospital and many other clinical hospitals. Its series of brain pacemakers have been under the leadership of Prof. Li Luming's team at Tsinghua University since 2000, and the first clinical trial was conducted in 2009. In 2014, Punch Medical obtained the product registration certificate for its full series of brain pacemakers (DBS), and in 2016, it obtained the CE certification. The development and launch of the Pinch DBS system broke the monopoly of foreign giants in the field of DBS therapy, and made China a country capable of researching, developing, producing, and applying pacemakers on a large scale, except for the U.S. In 2018, the project "Brain Pacemaker Key Technology, System and Clinical Application", which was born out of the model of industry, academia and medicine, won the National Scientific and Technological Progress Award in 2018, and was awarded the National Science and Technology Prize for the year. In 2018, the project "Key Technology, System and Clinical Application of Brain Pacemaker", which was born from this industry-university-research-medicine model, won the first prize of National Scientific and Technological Progress.
The Pinch series of brain pacemakers is a domestic DBS system with independent intellectual property rights, featuring technical advantages such as 3.0T MRI compatibility, inverter stimulation, remote programmed control, and significant price advantages.
(1) 3.0T MRI compatibility: Pinchot Brain Pacemaker will be able to realize high-field intensity MRI scanning under power-on condition;
(2) Variable-frequency stimulation: Combining traditional high-frequency stimulation and low-frequency stimulation, it can effectively control some of the midline symptoms, such as locomotor symptoms and freezing of gait, etc. It has been reported that this therapy has been proven in the preliminary clinical research and has been approved for the U.S. invention patent.
(3) Remote control: A "big center-subcenter" remote control system has been built, which is convenient for post-DBS patients to be controlled nearby, and allows patients to receive the whole Parkinson's disease treatment and rehabilitation therapy in nearby hospitals.
(4) Price Advantage: The per capita cost of Pinchuk DBS implantation can be more than 100,000 RMB lower than that of imported implantation.
2. Suzhou Jingyu Medical Series Brain Pacemaker - DBS system containing the first domestic neuromodulation chip
Suzhou Jingyu Medical Devices Co., Ltd. was founded in 2011 and is headquartered in Suzhou Industrial Park, and its founders used to work at GE Healthcare, Medtronic, Siemens, and other foreign-funded device companies. Since 2008, Jingyu's team has been working on the development of the DBS system, and in 2014, its brain pacemaker was included in the special approval channel for innovative medical devices by the national drug regulatory authority and was approved for marketing in 2016. According to the latest data on the company's official website, Jingyu Medical has been approved for 152 patents. Among them are 80 invention patents, 53 utility model patents, 2 design patents and 6 PCT international invention patents.
Jingyu Medical's series of brain pacemakers have the following advantages:
One is the independent research and development of the country's first chip in the field of neuromodulation, dual-frequency intellectual property rights chip technology, allowing the use of different stimulation parameters in different locations of the brain's nucleus accurately realize the left and right brain heterogeneous frequency programmable;
The second is the wireless remote programmable control technology, support for the doctor, patient
The second is the wireless remote control technology, which supports the interaction between the doctor and the patient, allowing the doctor to carry out remote control and complete the adjustment of the patient's pacemaker parameters;
The third is the electrode self-locking technology, which solves the thorny problem of electrode displacement for pacemakers, which is a common problem in clinical practice.
In addition to Parkinson's disease, Jingyu Medical is exploring ways to broaden the indications for DBS therapy, including obsessive-compulsive disorder, depression, and drug addiction.In 2017, the company's third-generation product, a brain pacemaker for treating drug addiction, was included in the Special Approval Channel for Innovative Medical Devices by the State Pharmaceutical Supervision and Regulation Department.In 2018 onwards, a multi-center clinical study including 60 subjects and DBS for the prevention of relapse after opioid withdrawal has been carried out in Tang Du Hospital, China Institute of Drug Dependence, Shanghai Ruijin Hospital and other hospitals and research institutes, led by Tang Du Hospital, China Institute of Drug Dependence and Shanghai Ruijin Hospital. Conclusion
DBS therapy has been used clinically for more than 30 years. Since its entry into China in the early 2000s, the domestic DBS market has basically been dominated by Medtronic, Poco, and St. Jude, which are the foreign-funded giants, and it was not until Pinchot, Jingyu, and other medical technology companies overcame the difficulties and developed domesticated cerebral pacemakers that the original monopoly pattern was broken.
In China's nearly 3 million Parkinson's disease patients this huge population base, with the DBS therapy applied to depression, obsessive-compulsive disorder, drug addiction and other diseases of the application gradually approved, the DBS field of the market space will also be further expanded. We believe that the domestic DBS system with obvious price advantage will gain more policy support and a larger audience by virtue of its eye-catching cost-benefit ratio.
Of course, the promotion of DBS therapy still faces many obstacles, such as low patient awareness and acceptance, high threshold of therapy, and expensive DBS consumables (often more than 200,000 RMB). For the first two limiting factors, enterprises can gradually improve the situation through patient education, operator training and training, etc.; for the huge financial burden faced by patients, it requires the collaboration of medical insurance, commercial insurance, enterprises and individuals to break the predicament. What is the development potential of deep brain stimulation (DBS) therapy and how will the market landscape change in the future? Let's wait and see!