New Drug LBT-3627 Increases Treatment Hope for Parkinson’s disease

Investigators who examined a new drug ( LBT-3627 ) in a mouse model of Parkinson’s disease demonstrated it can modify the behavior of immune cells so they protect dopamine-producing cells rather than attacking them.

Co-author Dr. Scott Shandler, co-founder and CEO of Longevity Biotech, states that:

“The outcomes are interesting as they offer a bridge between the immune system and nerve cell protection in Parkinson’s disease.”

Senior author Howard Gendelman, states that the idea for the drug was born almost one decade back, when it was identified that a kind of white blood cell was attacking the brain cells that are the cause for Parkinson’s disease. He adds:

“The new Longevity Biotech drug (LBT-3627) was capable to modify the function of these cells from eliminating the nerve cells to protecting them.”

The death of dopamine-producing cells in a part of the brain known as the substantia nigra pars compacta is a chief hallmark of Parkinson’s condition. Dopamine transports brain signals that manage a number of functions, such as movement.

As the harmful brain-wasting condition progresses, sufferers progressively lose their capability to walk, talk and take care of themselves.

Immune cells perform major role in Parkinson’s disease

Researchers have known for a while that Parkinson’s disease involves modifications to both dopamine and non-dopamine brain cells and their signaling pathways, as well as inflammatory modifications to microglia (innate immune cells in the central nervous system) and infiltration of T lymphocytes (a kind of WBC in the adaptive immune system).

Initially, they assumed some of the modifications – like those involving the microglia and the WBCs – were the outcome of injury instead of influencers of main events. But then, almost 10 years ago, investigators identified that both triggered microglia and WBCs play an essential role in neuro-degeneration in Parkinson’s disease.

The proof from that and other research shows the immune system can both protect and harm the brain. This has spurred much research into how to use this understanding to produce new therapies for Parkinson’s – a condition for which there is yet no cure.

The investigational drug LBT-3627 is very similar to a naturally occurring, well-established anti-inflammatory molecule known as VIP that is useful in a variety of disorders.

However, there have been issues with basing new medicines on VIP – one reason being it quickly degrades in the body. Another cause is that is not able to differentiate between its two naturally intended receptors – VPAC1 and VPAC2.

Receptors are molecules that get signals from outside the cell. They only bind to particular molecules known as agonists. Drug developers use this characteristic to make agonist drugs that modify cell behavior – in this case, to modify immune cells from acting in an inflammatory to an anti-inflammatory manner.

New drug obtained 80% protection of dopamine-producing cells

LBT-3627 is unique to VIP in two aspects: it particularly targets only one of the receptors, VPAC2, and it seems to last considerably longer than VIP in the body prior to degrading. It also has the benefit that it could be provided orally, making it more easier to administer in sufferers with Parkinson’s disease, states Dr. Shandler.

When they examined LBT-3627 in a mouse model of Parkinson’s disease, the team identified it could obtain up to 80% protection of dopamine-producing cells.

The team also identified that the medicine had an effect on the microglia cells, and that they were eventually accountable for the protective impact that halted the brain damage.

The developers are hoping to start a phase 1 clinical study of LBT-3627 in humans by 2017, after performing more animal trials.

Prof. Gendelman concludes:

“The key finding in our research was that a particular white blood cell subset was produced as a impact of LBT-3627 therapy and offered protection of dopamine-producing nerve cells from being harmed. The neurotoxic immune reaction was stopped and LBT-3627 was capable to prevent disease.”

There are about 10 million individuals globally living with Parkinson’s disease – roughly 1 million of them in the US, where about 60,000 individuals are diagnosed with the condition each year.

Another characteristic of Parkinson’s disease is the deposition and progressive spread of protein clumps known as Lewy bodies in the area of the brain most impacted by loss of dopamine cells. Some researchers are starting to think the protein clumps speed up the disease.