Parkinson’s Disease: 5 stages, Risk Factors, Prevention, Gene Therapy

Parkinson’s Disease is a condition that involves dysfunction or loss of dopamine-producing neurons in the brain. The hallmarks of this Disease are degeneration of dopaminergic neurons in the substantia nigra pars compacta of the midbrain and Lewy bodies presence, cytoplasmic aggregations of the protein a-synuclein in brain neurons. These features are related to the clinical signs of disease.
Dopamine is a neurotransmitter that helps the body’s ability to carry out a coordinated movement, the decreased levels of dopamine that underlie Parkinson’s Disease is characterized by difficulty with both voluntary and involuntary movements. The disease includes nonmotor symptoms such as depression, sleep disturbances, and orthostatic hypotension. Based on the disease onset among the patients, Parkinson’s disease classification includes Juvenile Parkinson’s Disease, Young-onset Parkinson’s Disease, and Idiopathic Parkinson’s Disease.

Parkinson’s Disease is hereditary or not?

Hereditary diseases are transferred from parents to their children through their genes. Some genetic diseases are caused due to random mutations, which are not inherited from the parents.

It is rare, but some of the cases of Parkinson’s Disease are hereditary. Different gene mutations cause the disease. Though most cases do not have known cause, the research alludes that Parkinson’s disease is caused because of genetic and environmental factors.

What are risk factors for Parkinson’s disease?

The risk factors for Parkinson’s disease are mutations in specific genes that associated with Parkinson’s disease, family history of Parkinson’s disease, people who are above the age of 60, exposure to herbicides and pesticides, sex, i.e. being male and etc.

What food suffering from Parkinson’s disease patients should consume?

Studies show that the food that patients suffering from Parkinson’s disease should consume the Mediterranean diet that focuses on fishes, vegetables, whole grains, fruits, olive oil, peanuts, and seeds, may decrease the risks. Also, limiting dairy and red meat may aid in decreasing the risks.

How Parkinson’s Disease can be prevented?

Though most causes of Parkinson’s disease are not known, so there are no specific prevention techniques. Parkinson’s disease can be prevented, as indicated by the research studies that caffeine and green tea may decrease the risk. Besides, being active may also lower the risk.

What Are the Stages of Parkinson’s Disease?

There are 5 stages and they are as follows:-

Stage one of Parkinson’s disease

Parkinson’s disease symptoms are mild and observed on one side of the body. The symptoms may be so minor that the person doesn’t need medical attention. Stage one of Parkinson’s disease symptoms are tremor, rigidity, on one hand, or leg. People may feel clumsy.

Stage two of Parkinson’s disease

Stage two is an early disease in Parkinson’s Disease, and symptoms are seen on both sides of the body. It may develop months or years after stage one occurs. Stage two of Parkinson’s disease symptoms include the facial expression loss on both sides of the face, lowered blinking, speech abnormalities, soft voice, and monotone voice. Though, the individual is still able to perform tasks of daily living at this stage. If the patient suffers a tremor, then the diagnosis may be easy.

Stage three of Parkinson’s disease

Stage three is mid-stage and is by loss of balance and slowness of movement occur. Balance is difficult to maintain as they are not  able to make the rapid, automatic and involuntary adjustments that are necessary to avoid falling, and falls are frequent at this stage. All other Stage three of Parkinson’s disease symptoms are also present at this stage, and generally, diagnosis is not in doubt. An essential factor is that the patient is independent in their daily living activities.

Stage four of Parkinson’s disease

In stage four, the disease has advanced to a severely disabling disease. Stage four of Parkinson’s disease patients may be able to walk and stand without support, but they are noticeably debilitated. At this stage, the patient can not live an independent life and needs support for some activities of daily living. If the patient is still able to live by himself/herself, it is still characterized as stage three.

Stage five of Parkinson’s disease

Stage five is the most advanced and a person cannot rise from a chair/bed without assistance; they may fall while standing and may stumble upon while walking. They need assistance every time to reduce the risk of falling and aid the patient with all daily activities. The patient may also have hallucinations or delusions.

Parkinson’s Disease Epidemiology

The female-to-male ratio for Parkinson’s disease prevalent cases varies between men and women. Males were having a high prevalence rate when compared to females. Already 10 million people are living with this disease. Parkinson’s disease incidence rises with age. Men are likely prone to the disease than women. Per 100,000 population, Parkinson’s disease incidence rate was more than eighty.

How Gene therapy helps in Parkinson’s disease

Gene therapy helps in Parkinson’s disease treatment by genetically modifying populations of cells that are either directly impaired or capable of reducing the disease symptoms. These genetic modifications can either increase or reduce the expression of specific genes or gene sets, or even restore the normal function of the product of these genes.
There is a slew of therapies that are being developed by many companies like Prevail Therapeutics, Axovant Gene Therapies, Denali Therapeutics, Neurocrine Biosciences, and others are researching new therapies.
One of the gene therapy is VY-AADC that is being developed by Neurocrine Biosciences in collaboration with Voyager Therapeutics. It is designed to put the AADC enzyme into brain cells where levodopa is converted to dopamine. The AADC gene is delivered into a transporter called “adeno-associated viral vector” (AAV).
Another Gene Therapy for Parkinson’s Disease is AAV-GAD by MeiraGTx Holdings. The therapy is a gene therapy medicine that is designed to deliver the GAD gene to increase GABA production, an inhibitory neurotransmitter in the human brain. In GABA synthesis, GAD is the rate-limiting enzyme. So, it is speculated that rising GAD expression by using gene therapy will result in motor circuits normalization and improve Parkinson’s disease symptoms in patients without affecting other brain regions.
AAV-GAD has got Fast Track designation from the U.S. Food and Drug Administration. This gene therapy is expected to introduce by 2024 in the United States.
Besides gene therapy, it was observed that stem cell therapy has a more effective Parkinson’s disease treatment option. Stem cell research is focusing on understanding nerve cells development, and how healthy cells can be used to replace damaged brain cells. It is possible to replace the unhealthy cells in the brain by an introduction of healthy dopamine-producing cells produced from stem cells grown in the laboratory. Healthy dopamine-producing cells derived from stem cells can be beneficial to researchers in testing new Parkinson’s disease treatments. These new therapies will make a significant impact on people living with Parkinson’s Disease.