Mitochondrial Dysfunction & Parkinson's Disease | Andy Lee, COO Vincere Biosciences

Live Longer World Podcast #15

"Vincere is a Latin term which means to conquer or to fight. So right off when we started the company, we wanted a constant reminder that this is a fight, that we are champions for patients, there are people who are looking for somebody that can get drugs into the clinic to stop the progression of this disease (Parkinson’s). So that is our guiding force, to win this fight to improve the lives of patients."

Live Longer World Podcast Episode #15 has been released!

My guest today is Andy Lee who is the Chief Operating Officer at Vincere Biosciences. Vincere is working to stop Parkinson’s disease by creating small molecules or drugs that target mitochondrial dysfunction. There is increasing evidence that a dysfunctional mitochondria can lead to the onset of Parkinson’s disease.

In today’s conversation, we discussed the science behind a dysfunctional mitochondria and mitophagy, the relationship between the mitochondria and Parkinson’s disease, and whether certain mitochondria boosting supplements like Urolithin A and Coq10 that delay the onset of Parkinson’s. We also discussed the biological simulation and computational biology platform used by Vincere - they use AI systems that can be used to screen drugs & targets and simulate cell environments. Finally, we spoke about the challenges with running a biotech company.

Andy comes from a background in technology and computer science background and he combined it with biology to create Vincere Biosciences.

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Want Summarized Notes on Key Points Discussed in the Podcast?

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Key points summarized below for premium subscribers include:

• The connection between Mitochondrial quality control & Parkinson’s disease

• Mitophagy and the science behind targeting the mitochondria

• Overview of the Biological Simulation Platform used by Vincere Bio

• Can compounds like Urolithin A & Coq10 that target the mitochondria delay Parkinson’s

• Challenges with running a Biotech company

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Listen to the Podcast:

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Spotify:

YouTube:

All Platforms: here

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Time Stamps:

0:00 Live Longer World Intro

0:34 Andy Lee & Vincere Bio Intro

1:55 Vincere & the connection between mitochondria & Parkinson's

7:39 Mitophagy & Parkinson’s disease

16:29 Role of USP30 in Mitochondria & Parkinson’s

22:26 Vincere small molecules testing

25:18 Other pathways affected during Parkinson's

30:53 Computation Biology Platform used by Vincere

36:50 Urolithin A & Coq10 to help with Parkinson’s

39:45 Biomarkers for Mitophagy

42:46 Too much mitophagy?

44:50 Challenges running a biotech company

48:19 Path forward for Vincere

49:36 Support, share and follow Live Longer World!

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Summarized Show Notes of Key Points:

The connection between Mitochondria Quality Control and Parkinson’s Disease:

Your company Vincere Biosciences is working on small molecules and drugs to stop Parkinson’s disease by targeting mitochondrial dysfunction. I want to dive into the science. But for some context, maybe you can explain what Vincere Bio is doing and how it came about?

• Vincere is a Latin term which means to win, so we want to win and be champions for patients who want to stop disease

• The focus on mitochondria is driven by human genetics at its core

• For Parkinson’s, most cases are not genetic, they are idiopathic, but you don’t have much of a clue what’s going on in the disease course

• You know what the end states of Parkinson’s are but you don’t know what causes it

• In human genetics, there are a set of mutations that cause the disease

  • There are about a dozen mendelian genes that cause parkinson’s so from that we can try to figure out where they overlap, to know what to target

• If you look at the overlap of these genetic communities, they overlap on mitochondria quality control, so it’s the most represented pathway in the set of pathways that are affected by Parkinson’s

• so this was the hypothesis that if we can improve mitochondrial quality control, there is a broad chance that we can help improve the state of Parkinson’s patients

• Age is the biggest risk factor for Parkinson’s and declining mitochondria quality is one of the hallmarks of aging, so that connection made sense too

• Inflammation is another pathway that has been implicated in Parkinson’s disease but not sure whether that is causative or downstream

Mitophagy and the mechanisms to deploy when targeting mitochondria:

Let’s discuss the science and mechanisms by which you aim to target the mitochondria. The way I understand it there are 3 main enzymes or factors: PINK1, Parkin and USP30. Can you explain what these factors are doing during the process of mitophagy?

• Mitophagy = degradation of damaged mitochondria

• Mitochondria naturally become dysfunctional with age. The life of a mitochondria is about 45 days

  • An average mitochondria lives for about 30-40 days before it’s cleared and replaced by new healthy ones through mitophagy

• When mitochondria becomes dysfunctional, the membrane becomes depolarized, leads to production of Reactive Oxygen Species (ROS) and don’t produce ATP well

• Having dysfunctional mitochondria in the cell is bad, it also leads to cellular senescence and inflammation

• Our bodies have developed a natural built-in quality to clear damaged mitochondria

  • There is a trigger to the cell to know which mitochondria is damaged because cell needs to know only to clear damaged mitochondria and not healthy ones

• So there is a protein called Parkin which is recruited via PINK1 and then Parkin activates the autophagy process