Parkinson's disease drug research and development is gradually heating up. Who can take the lead in breaking the situation with Ling, Luye, and Kangyuan?

As a neurodegenerative disease, Parkinson’s disease (PD) is the “third killer” that seriously threatens the health and lives of middle-aged and elderly people.

01 Introduction to Parkinson's Disease

Parkinson's disease (PD) is a degenerative disease of the nervous system characterized by neurodegeneration of the substantia nigra striatum pathway.

Epidemiological investigations have shown that the prevalence of Parkinson’s disease over 60 years old in Europe and the United States has reached 1%, and that of over 80 years old is over 4%.

Figure 1.

(Reference: Handbook of Clinical Neurology, History of Parkinson's disease)

02 Pathological Mechanism Research

The main pathological characteristics of PD patients are the damage of dopaminergic neurons in the substantia nigra compact area and the decrease of striatal dopamine content, which in turn causes the weakening of the dopamine innervation function of the substantia nigra-striatal pathway, and the relative cholinergic nerve function Enhancement, the patient has symptoms such as motor dysfunction.

The onset of PD is currently believed to be mainly related to age, environment and genetic factors.

Figure 2.

(Reference: Life Sciences 226 (2019) 77–90)

03 Drugs that have been approved for marketing

Up to now, there are about 25-30 anti-PD drugs approved by the FDA, involving multiple drug targets: for example, the dopaminergic system includes aromatic amino acid decarboxylase (AADC), catechol oxygen methyltransferase (COMT), and monoamine oxidase B (MAO-B), dopamine transporter (DAT), dopamine receptor (DR); serotonergic system includes serotonin 2A receptor (5-HT2A), 5-HT2C receptor; cholinergic system includes toxin Muscarinic acetylcholine receptor (mAChR); in addition, there are N-methyl-D-aspartate receptor (NMDAR), and so on.

Since the listing of levodopa in 1967, it has become the main treatment drug for PD motor symptoms, and from the current clinical application, there is no other DR agonist that can achieve the clinical effect of levodopa.

However, long-term use of levodopa can cause side effects such as symptom fluctuations, switching phenomena, and dyskinesias.

Table 3.

04 Drug treatment recommended by my country's guidelines

As above, there are a variety of drugs that can effectively improve Parkinson's disease in clinical practice.

The Chinese Parkinson’s Disease Treatment Guidelines (Fourth Edition) recommends: For patients with early-onset Parkinson’s disease without loss of intelligence, the following options are available: non-ergot DAs, MAO‑BI, compound levodopa, entacapone Dopa tablets, amantadine, anticholinergic drugs; with decreased intelligence, you should choose compound levodopa.

For patients with late-onset Parkinson's disease or early-onset patients with mental decline: compound levodopa is generally the first choice, and DAs, MAO-BI or COMTI can be added as symptoms worsen and the efficacy decreases.

Figure 4.

(Reference: Chinese Parkinson's Disease Treatment Guidelines (Fourth Edition))

05 Drugs under development in the domestic PD field

Currently, domestic pharmaceutical companies dedicated to the research and development of new PD drugs include Shandong Luye, Intech New Creation, Beijing Zhongyuan Hengkang Biotechnology, Dongyang Pharmaceutical, Jiangsu Kangyuan, Shijiazhuang Yiling, Zhejiang Chunhe Medicine, Institute of Pharmaceutical Sciences, Chinese Academy of Sciences, and Military Science Hospital Toxicology Institute, etc.

However, it is worth noting that the registration time of a variety appears roughly at two extremes.
One end is a variety that has not made obvious progress in the past 10 years, while the other end is mainly concentrated in the registration application in the past 2 years.
It can be seen that the research and development of drugs for Parkinson's disease in domestic pharmaceutical companies is gradually heating up, and looking at the process of domestic and even global population aging, drug research and development in this field will certainly receive more and more attention and investment from sponsors.
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reference:

1.
Handbook of Clinical Neurology, Vol.
83 (3rd series) Parkinson's disease and related disorders, Part I.
Chapter 5 History of Parkinson's disease

2.
Guidelines for the treatment of Parkinson's disease in China (fourth edition)

3.
J Med Postgra, Vol.
32, No.
6, June, 2019.

4.
Parkinson's disease: Mechanisms, translational models and management strategies.
Life Sciences 226 (2019) 77-90.