MetAP2 Inhibition for Aging

(BIO-AGE Trial)

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: AdventHealth Translational Research Institute

Must not be taking: Insulin, Metformin, Anti-inflammatories, Antiplatelets

Disqualifiers: Diabetes, Hypertension, Alcohol abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how MetAP2 inhibition, a drug targeting a specific enzyme, affects fat tissue in the lab. It includes participants aged 18-30 and those 65 and older. The goal is to determine if the treatment impacts aging by using fat samples from participants. Ideal candidates are individuals not actively trying to lose weight and who have maintained a stable weight for the past three months. As an unphased trial, this study allows participants to contribute to groundbreaking research on aging and fat tissue.

Will I have to stop taking my current medications?

The trial requires that you stop taking anti-inflammatory medications 2 days before a biopsy and antiplatelet medications 7 days before a biopsy, if they cannot be safely stopped for study procedures. Other medications are not specifically mentioned, so it's best to discuss with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that MetAP2 inhibitors have undergone safety testing in humans. One study found that these inhibitors can aid weight loss without causing serious side effects. Another study demonstrated that using a MetAP2 inhibitor for 26 weeks resulted in significant weight loss, indicating general tolerability.

Researchers have explored these inhibitors for treating various conditions due to their potential to aid weight loss and possibly extend lifespan. While effects can vary, evidence suggests that MetAP2 inhibitors are likely safe, with no major negative effects reported in these studies. ^{1 2 3 4 5}

Why are researchers excited about this trial?

MetAP2 inhibition is unique because it targets the MetAP2 enzyme, which plays a role in cellular aging processes. Unlike traditional anti-aging treatments that focus on lifestyle changes or antioxidant supplements, this approach directly affects the biochemical pathways related to aging. Researchers are excited about MetAP2 inhibition because it offers the potential to slow down aging at the cellular level, which could lead to improved health and longevity. Additionally, this treatment is being tested across different age groups, which may help to understand its effectiveness and potential benefits for both younger and older individuals.

What evidence suggests that this trial's treatments could be effective for aging?

This trial will examine the effects of MetAP2 inhibition on aging. Research has shown that blocking a protein called MetAP2 can significantly impact body weight and lifespan. Studies have found that MetAP2 blockers aid weight loss by reducing food intake and increasing energy expenditure. They also appear to increase muscle mass while reducing fat, particularly in overweight mice. Additionally, these blockers have been linked to longer lifespans in animal studies. MetAP2 blockers can lower inflammation by reducing certain inflammatory molecules. Overall, these findings suggest that MetAP2 blockers might help reduce age-related health problems and improve quality of life. Participants in this trial will be divided into groups based on age and whether they receive MetAP2 inhibition. ^{1 4 5 6 7}

Who Is on the Research Team?

Lauren Sparks, PhD

Principal Investigator

Study Principal Investigator

Are You a Good Fit for This Trial?

This trial is for healthy young adults aged 18-30 and seniors 65 or older with a BMI ≤ 40 kg/m2, who are sedentary, weight stable, and can understand English. They must be willing to follow the study plan. People with drug/alcohol abuse history, unstable medical conditions, recent tobacco use, certain allergies or infections like HIV/Hepatitis B/C, diabetes, untreated hypertension or those on specific medications cannot join.

Inclusion Criteria

Body mass index (BMI) ≤ 40 kg/m2

Willing and able to comply with scheduled visits, laboratory tests, and other study procedures

I exercise less than 20 minutes, three times a week.

Exclusion Criteria

Tobacco or nicotine containing product use within the past 3 months

Presence of any condition that, in the opinion of the Investigator, compromises participant safety or data integrity or the participant's ability to complete study visits

I have type 2 diabetes with an HbA1C level of 6.5 or higher.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Sample Collection

Adipose tissue is collected from young and older individuals for laboratory analysis

1 week

1 visit (in-person)

Laboratory Analysis

Analysis of the effect of MetAP2 inhibition on adipose tissue in the laboratory

4 weeks

Follow-up

Participants are monitored for any post-sample collection effects

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MetAP2 Inhibition

Trial Overview The study aims to collect fat tissue from participants to examine how blocking a protein called MetAP2 affects it in the lab. This could help understand aging-related changes in body fat.

How Is the Trial Designed?

Group I: Younger with MetAP2 inhibition Experimental Treatment 1 Intervention

Participants between 18 and 30 years old with MetAP2 inhibition in conditioned media

Group II: Older with MetAP2 inhibition Experimental Treatment 1 Intervention

Participants 65 years old with MetAP2 inhibition in conditioned media

Group III: Younger without MetAP2 inhibition Active Control 1 Intervention

Participants between 18 and 30 years old without MetAP2 inhibition in conditioned media

Group IV: Older without MetAP2 inhibition Active Control 1 Intervention

Participants 65 years old and without MetAP2 inhibition in conditioned media

Who Is Running the Clinical Trial?

AdventHealth Translational Research Institute

Lead Sponsor

Trials

51

Recruited

5,900+

Published Research Related to This Trial

In a study of 2344 patients in Phase II trials, 22% were aged 65 or older, and while elderly patients experienced higher rates of dose delays and reductions, they did not show increased rates of severe hematological toxicity compared to younger patients.

Elderly patients did experience more severe oral toxicity and alopecia, but overall, they had similar response rates to treatment as younger patients, suggesting that age alone should not exclude them from clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Entry and evaluation of elderly patients in European Organization for Research and Treatment of Cancer (EORTC) new-drug-development studies. Monfardini, S., Sorio, R., Boes, GH., et al.[2019]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1043276025001985

Methionine restriction and mimetics to ameliorate human ... Methionine restriction (MetR) attenuates the severity of numerous age-related diseases and extends lifespan across multiple species.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7741419/

Longevity-Extending MetAP2 Inhibitors Induce Caloric ... Inhibitors of MetAP2 cause profound weight loss secondary to decreased food intake. These inhibitors also significantly extend longevity in mice ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6579473/

MetAP2 inhibition increases energy expenditure through ... Using compounds with diverse chemical scaffolds, we showed that MetAP2 inhibition decreases body weight and fat mass and increases lean mass in the obese mice ...

4. mdpi.com mdpi.com/1420-3049/30/3/620

Methionine Aminopeptidase 2 (MetAP2) Inhibitor BL6 ... We found that BL6 reduced proinflammatory molecules, such as nitric oxide, iNOS, IL-1β, and IL-6, together with phospho-Akt and phospho-NF-κB p65.

5. ajp.amjpathol.org ajp.amjpathol.org/article/S0002-9440(10)61743-9/fulltext

Methionine Aminopeptidase-2 Regulates Human ... These results indicate that MetAP2 is a main regulator of proliferative and apoptotic pathways in mesothelioma cells.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3944999/

Inhibition of the methionine aminopeptidase 2 enzyme for the ... Clinical data of beloranib indicate that MetAP2 inhibitors could be a future treatment option for weight reduction without serious adverse ...

7. link.springer.com link.springer.com/article/10.1007/s00125-018-4677-0

a randomised, placebo-controlled clinical trial | Diabetologia Here, we report that treatment with a MetAP2 inhibitor for 26 weeks produced placebo-corrected clinically meaningful weight loss (−10%) and ...