Doctors circumspect about early success of oral pill against Parkinson’s Disease

It found that the oral pill, named Denali 201, 151 (DNL201, DNL151), blocks the accumulation of the enzyme known as LRRK2.

What is Parkinson’s Disease?

Parkinson’s Disease (PD) is a type of nervous system disorder that affects movement and the ability of the body to perform daily activities.

It also slowly damages the central nervous system, comprising the brain and the spinal cord. This also affects the motor system of the body.

It is the second-most-occurring neurodegenerative disorder in the world after Alzheimer’s Disease.

An enzyme named leucine-rich repeat kinase (LRRK2) is the risk factor behind PD, and is the target of the drug.

LRRK2 is also known as dardarin (from the Basque word “dardara”, which means trembling).

A variance of this enzyme is associated with an increased risk of Parkinson’s Disease.

The trial

The oral medication, aimed at slowing the advance of Parkinson’s Disease, was administered to rats, macaque monkeys, and 150 people over 28 days.

The drugs administered were DNL201 and DNL151. They work by preventing the accumulation of the LRRK2 enzyme.

Parkinson’s disease can occur when LRRK2 enzymes in the brain accumulate at such high levels that they damage lysosomes.

Mutations in LRRK2 are precursor events of dysfunction.

Lysosomes are sphere-shaped organelles that remove toxins from the brain. They are also called waste managers of cells. Their dysfunctionality leads to the buildup of toxic proteins in the brain, affecting cells.

According to Kerala-based consultant neurologist Dr Sreekumar J, most patients of PD report low levels of neurotransmitters like dopamine.

The aforementioned research is an early-stage clinical trial that is unlikely to restore the dopamine-producing affected neurons, he said.

Moreover, the low count of patients with dysfunctional lysosomes is an existing limitation of the trial, added the doctor.

Besides, low concentrations of dopamine are also starting to be linked to Parkinson’s disease.

Results

Here’s what the researchers found:

Regulation of lysosomal function due to the impact of the experimental pill was observed in both animals and humans.

• Therapeutic approaches to tackle Parkinson’s Disease were found impactful.
• The drug was found to be restoring the lysosome size and morphology.
• It was also reducing the degradation of lysosomes.
• After being administered to humans and monkeys, the drug was found safe.

Bengaluru-based neurologist Dr Abbas M told South First, “At present, there are estimated 49-50 drugs in trial to treat Parkinson’s, and the majority of them are facing glitches in phase 3 and long-term experiments. As of now, the overall effort of the scientific community is to target disease progression.”

Chennai-based neurologist Dr Sushanth Selvam considers the experiment as critical progress.

He said, “Exact risk factors behind Parkinson’s occurrence are unknown. The two reasons are dopamine depletion and lysosomes affected by the toxicity of other proteins. The present trial partly claims to protect or restore the functions of lysosomes with no result on dopamine.”