MEDICINE AND HEALTH

Smell “incense” to recognize Parkinson’s disease Researchers at Xiangya Hospital of Central South University found for the first time that dogs can help sniff Parkinson’s disease


18 years ago, when Dr. Gao Changqing, director of the Animal Experiment Center of Xiangya Hospital of Central South University, first received the Belgian shepherd dog “David”, he did not expect that this strong and beautiful dog could become a good assistant to help doctors identify Parkinson’s disease patients.

Today, he has done so through a series of research projects with multiple teams.

Previous scientific research has suggested that patients with Parkinson’s disease may have a specific odor. In the past few years, the team of Professor Guo Jifeng and Professor Tang Beisha, Department of Neurology of Xiangya Hospital, and three other third-class hospitals in the United Nations, carried out a multi-center, prospective, double-blind clinical trial, and found that Belgian shepherds can smell the similar musky odor of the skin of Parkinson’s disease patients, which provides a new idea for the diagnosis of Parkinson’s disease.

Recently, this original research result was published in Movement Disorders in the form of a cover paper, with Gao Changqing and Guo Jifeng as the co-corresponding authors of the paper, Gao Changqing as the first author, and Xiangya Hospital as the first unit author and first corresponding author unit. It is reported that this is the world’s first report confirming the use of laboratory animals to assist in the diagnosis of human Parkinson’s disease.

The above scientific research results were published in the form of a cover paper in “Movement disorders”. Image from “Movement Disorders”

Gao Changqing said frankly that without the study and work experience in Belgium, it would be difficult to achieve today’s results. Gao’s story begins when he was in graduate school.

First encounter with a dog

Belgium, a romantic country in Western Europe.

Gao Changqing, a native of Hunan, came to Belgium in 1993 to pursue a PhD through TOEFL and GRE at the Heymans Institute of Pharmacology, Faculty of Medicine, Ghent University.

The Heymans Institute is a research institute with a glorious history. The 1938 Nobel Prize in Physiology or Medicine was awarded to Corneille Heymans, the founder of pharmacology and therapeutics at Ghent University. Gao Changqing was the second Chinese scholar to carry out scientific work at the Heymans Institute at that time.

Professors from the Heymans Institute in exchange. Photo courtesy of interviewee

From 1993 to 2007, Gao Changqing studied and worked in Belgium. More than 10 years of foreign research life is busy and fun, but the most memorable thing for him is a walking trip in the evening.

“That day, I went for a walk near the institute after doing the experiment, and I accidentally saw an old grandfather walking a dog on the lawn, and he was very beautiful.” This made Gao Changqing instantly interested.

Belgian Shepherd. Photo by Wang Haohao

Gao Changqing has a special affection for dogs, in his words, “born to like dogs”. When he was studying in Belgium, he often watched the National Physical Geography Channel and watched the show about military dogs regularly every week. “I particularly enjoy watching how military dogs such as German Shepherds find mines, find traps, and take humans out of their way.” Gao Changqing sighed, those military dogs are too smart.

At the same time, Gao Changqing will also focus on news related to therapy dogs, such as using dogs to treat autistic children.

Compared with the German Shepherd, Gao Changqing prefers the grandfather’s dog, which has a well-proportioned body structure, a light and graceful gait, and good obedience. One day, he finally couldn’t help but step forward and communicate with the dog owner, hoping to have such a dog too.

Seeing that Gao Changqing is a foreigner who is not fluent in Dutch, the dog owner is not very “cold” to him, and continues to walk the dog. Gao’s first “pick-up” ended in failure.

“I thought to myself, I must have a dog like this.” Gao Changqing said that after “squatting a little” many times after work, he found that the old man would come to walk his dog near the institute almost every weekend, “Every time I met, I would talk to him and slowly get acquainted.” ”

After checking the information, it turned out to be a short-haired Belgian shepherd. Slightly smaller in size than the German Shepherd, this breed is very intelligent, alert, always faithful to its owner, and does not have the problem of dislocating the German Shepherd’s hind crotch. Due to its ferocious nature, there are not many locals owned, but it is the main police dog breed in Europe.

When Gao Changqing voiced his desire to own a Belgian Shepherd, the dog owner declined him. “It turns out that this dog owner specializes in training police dogs in Belgian police stations and does not sell them to ordinary people. The sale price to the police station was as high as more than 1 million francs. Gao Changqing said that at that time, a villa in Belgium was only about 4 million bilangs, and a few dogs could reach a villa.

The high price and the dog’s owner’s polite refusal deterred Gao Changqing, but he did not stop loving Belgian Shepherds. “I have been improving my relationship with the dog owner in various ways, such as introducing him to our Chinese culture, sharing food, and recommending him to participate in some cultural activities organized by the Chinese Embassy in Belgium.” Gao Changqing said.

Finally, the dog owner was impressed by Gao Changqing’s enthusiasm and persistence, and he decided to breed a Belgian Shepherd dog specifically for Gao Changqing. In 2004, Gao Changqing got his wish and named his dog “David”.

Gao Changqing and his dog David. Photo courtesy of interviewee

Get inspired

After owning a dog, Gao Changqing applied all kinds of dog training knowledge he had learned on TV and magazines, and took his dog out for training whenever he had time.

At that time, the medical community had already reported examples of dogs “smelling” diseases such as cancer in their owners. Gao Changqing has also done research on the Belgian Shepherd’s sense of smell and related medical cases of dogs sniffing human diseases.

Before the 20th century, Belgian shepherds were widely used in Belgium to guard sheep, guard and herd herds. In World War II, thousands of Belgian Shepherds served in the army, and they were used as herald dogs, reconnaissance dogs, border patrol dogs and field rescue dogs. Today, Belgian Shepherds are used as shepherd dogs, guard dogs, police dogs, tracking dogs, search and rescue dogs, customs drug search dogs, etc.

Today, Belgian Shepherds are used as shepherd dogs, guard dogs, tracking dogs, etc. Photo by Wang Haohao

Belgian Shepherds are nervous, alert and focused, sensitive and impulsive, particularly responsive to stimuli, loyal to their owners, and occasionally aggressive towards strangers. It is energetic and requires a lot of exercise.

Belgian Shepherds are nervous, alert, focused, sensitive and impulsive. Photo by Wang Haohao

“The Belgian Shepherd’s strong excitability determines that it is very willing to work, so it is mostly used as a working dog.” Gao Changqing said that the nose structure of dogs and humans is different, and there is a filtration process after the dog smells the smell into the airway, and the gas is transmitted to the lungs after filtration. “The biggest feature of the Belgian Shepherd is that the nose is very long, and the long nose will have a long nasal cavity, and the olfactory cells on the nasal cavity will be more, and the olfactory nerves will be richer.”

“Compared with the olfactory epithelium of about 10cm2 in humans, the olfactory epithelium area of dogs is more than 170cm2, which is 17 times that of humans; Dogs have more than 200 million olfactory receptors, 40 times more than humans. The dog’s olfactory receptors are more innervated, and the special structure of the nose makes it easy for it to distinguish the smell it inhales and exclude unwanted odors. Gao Changqing added.

Belgian Shepherds have longer nasal passages. Photo courtesy of interviewee

Gao Changqing introduced that as early as 1989, The Lancet reported a case of dogs sniffing human diseases, probably the content of a British man with a mole on his leg, but there was no lesion for a long time, one day, his dog began to lick the mole and try to bite the mole off, which attracted the attention of the owner. The Englishman only learned that he had malignant melanoma after seeking medical attention.

In 2001, the Lancet reported a similar medical case, which attracted the attention of scientists around the world. Subsequently, some scientific teams began to carry out related research, a British urology surgeon gave the urine of patients with bladder cancer to the training dog to smell, and found that it could accurately sniff the urine of bladder cancer patients.

In fact, the Nobel Prize-winning Cornell Haymens, through animal experiments, discovered the role of the aortic body and carotid sinus in regulating breathing, and found the neural mechanism to regulate respiratory activity, and the object of his experiments was dogs.

After 2001, there were international reports of dogs that could smell human diseases. This gives Gao Changqing a revelation, can his dog also sniff human diseases?

Coincide with

In 2007, Gao Changqing returned to China to work at Central South University, and successively served as the head of the Third Xiangya Hospital of Central South University and the Animal Experiment Department of Central South University, which gave him the opportunity to realize his ideals.

A view of Xiangya Hospital of Central South University. Photo by Wang Haohao

After becoming the director of the Department of Laboratory Zoology at Central South University in 2011, Gao Chang began dog training.

“In the first few years, our work focused on research into sniffing lung cancer in dogs. During the training, I found that dogs have a ‘thinking’ expression when they smell a specimen of a lung cancer patient. This convinced me that we could do something about the study of dogs sniffing human diseases. Gao Changqing said.

Gao Changqing’s first original record book of canine olfactory lung cancer discrimination. Photo by Wang Haohao

In 2016, reports suggested that Parkinson’s patients may have a specific odor. Gao Changqing found Professor Tang Beisha, a well-known neurologist in China and professor of neurology at Xiangya Hospital, hoping to cooperate in research. Professor Tang introduced Gao Changqing to his student, Director Guo Jifeng, who specializes in neurodegenerative diseases such as Parkinson’s disease. Once exchanged, the two coincided: if it can be confirmed that the Belgian Shepherd can assist the diagnosis of Parkinson’s disease by smelling the smell of Parkinson’s disease patients, it will provide new ideas for the treatment of Parkinson’s disease.

Guo Jifeng introduced that Parkinson’s disease is a common neurodegenerative disease. Its diagnosis has always been a difficult problem, theoretically speaking, the patient’s deep brain tissue needs to be taken for pathological examination to confirm the diagnosis, which is difficult to complete when the patient is alive.

“The incidence of Parkinson’s is about 1% of the entire population, and the number of Parkinson’s patients will increase as we age.” Guo Jifeng said that the clinical manifestations of Parkinson’s disease are mainly slow, shaky, stiff, hard, such as doing things slowly, moving very stiffly, trembling hands, and walking instability in the terminal stage, seriously affecting the quality of life.

Guo Jifeng (2nd from left) and Gao Changqing (1st from left) during ward rounds. Photo by Wang Haohao

Guo Jifeng said that Parkinson’s disease also has many non-motor symptoms, such as olfactory disorders, Parkinson’s patients may have a decline in olfactory ability 10 to 15 years before the onset of motor symptoms; There will besleep disorders, many patients have nightmares when they sleep at night, and even punch and kick, fall under the bed; Urinary or digestive symptoms, such as bloating, abdominal pain, constipation, or poor urination, may also occur. “The extremely complex clinical manifestations of Parkinson’s disease determine that it is very difficult to diagnose; Moreover, the patient was pathologically in the middle and late stages of the disease at the time of presentation. ”

In order to explore the role of body odor in the diagnosis of Parkinson’s disease patients, Xiangya Hospital of Central South University took the lead and carried out a multi-center, prospective, double-blind clinical trial in conjunction with the Third Xiangya Hospital of Central South University, the Second Affiliated Hospital of South China University and BenQ Hospital Affiliated to Nanjing Medical University.

Sniff for Parkinson’s disease

The study used dog sniffing to identify two groups of people from the four hospitals mentioned above (the first group included 109 patients with Parkinson’s disease treated with medication and 654 normal controls; The second group included 37 untreated patients with untreated Parkinson’s disease and 185 normal controls with a duration of less than 2 years) to explore the sensitivity and specificity of dog sniffing to identify patients with Parkinson’s disease.

Gao Changqing trains Belgian Shepherd Dogs. Photo by Wang Haohao

The results of the study showed that when two or all three sniffing dogs were used as positive results in the first group of patients treated with the drug, the sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of the test were 91%, 95%, 19.16 and 0.10, respectively. At the same time, the sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of untreated new-onset patients were 89%, 86%, 6.6 and 0.13, respectively.

More significantly, when further testing of trial participants who thought they were normal but dogs sniffed as Parkinson’s disease, it was found that most of them had more or less early clinical manifestations of Parkinson’s disease. This suggests that dogs can sniff out early Parkinson’s patients.

After sniffing the patient’s specimen, the Belgian Shepherd will stand by the jar it believes is the patient’s specimen. Photo by Wang Haohao

Postuma, an internationally renowned Parkinson’s disease expert and professor at McGill University in Canada, who is the corresponding author of the International Guidelines for the Diagnosis of Parkinson’s Disease, said: “This is really a very ingenious study. I think it’s reliable. ”

The reporter of “China Science News” saw at a dog sniffing scene that the scientific research assistant put a jar containing several specimens in the laboratory, one of which was a specimen of a clinically confirmed Parkinson’s patient. After placement, dog handlers who are not involved in the entire preparation process bring the sniffer dog into the laboratory and let it sniff samples from multiple jars for Parkinson’s disease. The dog can quickly locate the identification jar in which the patient’s sample is placed.

Scientific assistants place specimens. Photo by Wang Haohao

Specimen placement preparation. Photo by Wang Haohao

Belgian Shepherds can quickly locate the identification jar in which the patient’s sample is placed and stick its head into the jar for confirmation by the dog handler. Photo courtesy of interviewee

So, what exactly does Parkinson’s disease smell like? In this regard, Gao Changqing said that this is a taste similar to musk, but its specific molecular mechanism is not clear, which is also the future research direction of the team.

“From a clinical point of view, this study provides a new perspective on the diagnosis of Parkinson’s, which is rare.” Guo Jifeng said that experiments have shown that the sensitivity and specificity of dog smell discrimination Parkinson’s disease are high, and through the clinical transformation of this phenomenon, the team may develop diagnostic and differential diagnosis methods with clinical application prospects in the future.

“Traditional animal experiments mostly make models, give drugs or operate on animals, and then observe and compare the differences between the experimental group and the control group animals, which will cause certain harm to the animals. Our animal experiments do no harm to animals, and we are friendly to animals while animals contribute to humans. Gao Changqing said.

At present, there are 8 sniffing dogs in the Animal Experiment Center of Xiangya Hospital. Talking about the future, Gao Changqing said that the team is actively communicating with different departments and will strive to provide new clues for the diagnosis and treatment of tumors, metabolic diseases and other diseases through further canine smell animal experiments. (Source: Wang Haohao, China Science News)

Related paper information:https://doi.org/10.1002/mds.29180



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