Harnessing the glucose lowering actions of a-melanocyte stimulatory hormone as a potential new adjunctive therapy for people with type 2 diabetes
Lead Research Organisation:
UNIVERSITY OF ULSTER
Abstract
Context
There are 4 million people living with type 2 diabetes mellitus (T2DM) in the UK and 483 million worldwide. One of the core elements of the management of T2DM is the control of blood glucose levels. Poor control of blood glucose leads to the serious complications of T2DM, including kidney failure, blindness and amputations. These complications cause suffering to the individual and are very costly to the National Health Service.
Despite recent development and use of modern medications to control blood glucose, 69% of people with T2DM in the UK do not meet blood glucose targets. This figure demonstrates the critical unmet need for novel, safe and effective medication to control blood glucose.
Challenge
Any new medications for T2DM needs to be safe and effective, work alone or in combination with existing therapies and be a treatment option for all patients with T2DM independently of how advanced their disease is. The proposed experimental medicine project will enable us to take the first critical step in addressing these challenges in the drug development process.
We have discovered that a hormone naturally released from the brain, called alpha-melanocyte stimulatory hormone (a-MSH), reduces blood glucose. We administered a-MSH for the first time in animals and humans, and found that it:
i. Decreases blood glucose in animals and humans that are either healthy or have Type 1 diabetes mellitus (T1DM), by increasing the uptake of circulating glucose by muscle.
ii. Decreases blood glucose by 23% in a preliminary study of a small number of people with T2DM.
iii. Is safe, well tolerated, and does not cause low blood glucose (hypo).
In our journey to develop a new treatment for T2DM, we want to take the next step and:
i. Confirm that a-MSH reduces blood glucose in a larger number of people with T2DM.
ii. Understand how a-MSH works to reduce blood glucose.
By filling these gaps in our scientific knowledge, we will systematically progress towards the development of a medication that mimics the mechanism of action of a-MSH, and can be used as a safe and effective treatment for people living with T2DM.
Aims
i. Confirm that a-MSH reduces blood glucose in people with T2DM
ii. Understand how a-MSH works to reduce blood glucose.
Objectives
Work Package 1
Objective 1.1: Confirm that the intravenous infusion of a-MSH reduces blood glucose after a meal in people with T2DM.
Objective 1.2: Test whether the intravenous infusion of a-MSH reduces blood glucose by increasing its uptake by muscle in people with T2DM.
Work Package 2
Objective 2: Identify the receptor(s) and “machinery” a-MSH activates in muscle to increase the uptake of glucose from the bloodstream.
Applications and Benefits
The significance of this work is that it will provide definitive evidence as to whether a-MSH holds promise as a potential new treatment for T2DM. If our findings are positive, we will be well positioned to seek further funding to develop and optimise medication that work on the a-MSH receptor(s) in muscle to reduce blood glucose in people with T2DM. In the future, this could have a beneficial impact on the lives of people living with T2DM, their families and carers. A safe and effective treatment would enable people with T2DM to improve their glucose control and reduce their risk of developing the serious complications of T2DM.
There are 4 million people living with type 2 diabetes mellitus (T2DM) in the UK and 483 million worldwide. One of the core elements of the management of T2DM is the control of blood glucose levels. Poor control of blood glucose leads to the serious complications of T2DM, including kidney failure, blindness and amputations. These complications cause suffering to the individual and are very costly to the National Health Service.
Despite recent development and use of modern medications to control blood glucose, 69% of people with T2DM in the UK do not meet blood glucose targets. This figure demonstrates the critical unmet need for novel, safe and effective medication to control blood glucose.
Challenge
Any new medications for T2DM needs to be safe and effective, work alone or in combination with existing therapies and be a treatment option for all patients with T2DM independently of how advanced their disease is. The proposed experimental medicine project will enable us to take the first critical step in addressing these challenges in the drug development process.
We have discovered that a hormone naturally released from the brain, called alpha-melanocyte stimulatory hormone (a-MSH), reduces blood glucose. We administered a-MSH for the first time in animals and humans, and found that it:
i. Decreases blood glucose in animals and humans that are either healthy or have Type 1 diabetes mellitus (T1DM), by increasing the uptake of circulating glucose by muscle.
ii. Decreases blood glucose by 23% in a preliminary study of a small number of people with T2DM.
iii. Is safe, well tolerated, and does not cause low blood glucose (hypo).
In our journey to develop a new treatment for T2DM, we want to take the next step and:
i. Confirm that a-MSH reduces blood glucose in a larger number of people with T2DM.
ii. Understand how a-MSH works to reduce blood glucose.
By filling these gaps in our scientific knowledge, we will systematically progress towards the development of a medication that mimics the mechanism of action of a-MSH, and can be used as a safe and effective treatment for people living with T2DM.
Aims
i. Confirm that a-MSH reduces blood glucose in people with T2DM
ii. Understand how a-MSH works to reduce blood glucose.
Objectives
Work Package 1
Objective 1.1: Confirm that the intravenous infusion of a-MSH reduces blood glucose after a meal in people with T2DM.
Objective 1.2: Test whether the intravenous infusion of a-MSH reduces blood glucose by increasing its uptake by muscle in people with T2DM.
Work Package 2
Objective 2: Identify the receptor(s) and “machinery” a-MSH activates in muscle to increase the uptake of glucose from the bloodstream.
Applications and Benefits
The significance of this work is that it will provide definitive evidence as to whether a-MSH holds promise as a potential new treatment for T2DM. If our findings are positive, we will be well positioned to seek further funding to develop and optimise medication that work on the a-MSH receptor(s) in muscle to reduce blood glucose in people with T2DM. In the future, this could have a beneficial impact on the lives of people living with T2DM, their families and carers. A safe and effective treatment would enable people with T2DM to improve their glucose control and reduce their risk of developing the serious complications of T2DM.