ALS, amyotrophic lateral sclerosis, is a group of neurodegenerative diseases. ALS causes neurons in the motor cortex, brain stem and spinal cord to die. The influence on nerve cells in ALS is linked to the accumulation of a number of different types of proteins in the nerve cells. Common symptoms include a creeping muscle weakness that spreads to different parts of the body, ultimately resulting in paralysis. The muscles atrophy. Just over 200 people fall ill with the disease in Sweden every year, most between the ages of 45 and 75. The median survival time is two to four years. There is no treatment available to slow down the disease.

Our new results show that there are specific changes in the hypothalamus, and that these may be linked to affected metabolism, sleep and altered emotional regulation in ALS

Åsa Petersén, Professor of Neuroscience at Lund University, senior physician in psychiatry and the person responsible for the study, which has now been published, wanted to investigate the link between metabolism and ALS.

ALS, amyotrophic lateral sclerosis, is a group of neurodegenerative diseases. ALS causes neurons in the motor cortex, brain stem and spinal cord to die. The influence on nerve cells in ALS is linked to the accumulation of a number of different types of proteins in the nerve cells. Common symptoms include a creeping muscle weakness that spreads to different parts of the body, ultimately resulting in paralysis. The muscles atrophy. Just over 200 people fall ill with the disease in Sweden every year, most between the ages of 45 and 75. The median survival time is two to four years. There is no treatment available to slow down the disease.

Our new results show that there are specific changes in the hypothalamus, and that these may be linked to affected metabolism, sleep and altered emotional regulation in ALS

Åsa Petersén, Professor of Neuroscience at Lund University, senior physician in psychiatry and the person responsible for the study, which has now been published, wanted to investigate the link between metabolism and ALS.

- There is a clear link between metabolism and ALS, even though the underlying mechanisms are not known. One risk factor for falling ill with ALS is a slim physique, while a high BMI offers protection. Previous studies have identified that increased metabolism is linked to a faster progression of the ALS disease. But it’s also been noted that in addition to muscle weakness and altered metabolism, affected individuals can also have their sleep affected and poorer emotional regulation, says Åsa Petersén. 

Research has shown that ALS is part of a spectrum of diseases that also include frontal lobe dementia, and that one common denominator is the way neurons are attacked by the protein TDP-43 (TAR DNA-binding protein 43). This is a protein that has important functions in nerve cells that regulate genes expression and how substances are transported inside the cells. It is not yet fully understood how TDP-43 causes these neurodegenerative diseases.  

Collaboration with Australia

Metabolism, sleep and emotional regulation are controlled by the brain's hormone centre, the hypothalamus. Petersén’s research group has a successful collaboration going back many years with the Faculty of Medicine’s new honorary doctor, Professor Glenda Halliday from the University of Sydney. Halliday is an internationally leading authority in the field of neurodegenerative diseases. In studies already published, this collaboration has identified disease changes in the hypothalamus specifically in frontal lobe dementia and in Huntington’s disease, another neurodegenerative disease.

Sanaz Gabery, a postdoctoral student funded by the Swedish Brain Foundation and a prospective doctor, has conducted the analyses of brain tissue from ALS patients that led the researchers to the new hypothesis about the role of the hypothalamus in ALS. “Our hypothesis was that the hypothalamus is also affected in ALS, and that specific nerve cell groups that control metabolism, sleep and emotional regulation are damaged.

The studies were conducted in Petersén’s laboratory in Lund on brain tissue from deceased ALS patients in Sydney and on healthy control tissue. The studies were made possible thanks to unique and very systematically collected clinical material from the research environment and brain banks in Australia that Professor Glenda Halliday has worked to build up over many years. One of the lead authors, Dr Rebekah Ahmed, a neurologist, has collected clinical data from these individuals at the ALS clinic in Sydney, where she works.

- Our results show that the hypothalamus is smaller in patients with ALS and that nerve cell groups that manufacture substances that regulate metabolism, sleep and emotions are damaged. These substances are orexin and oxytocin. These particular nerve cells also affected by accumulations of a protein associated with the disease called TDP-43, says Sanaz Gabery.

Wants to identify new lines of attack

In another international collaboration, Åsa Petersén has shown that the hypothalamus is smaller on MRI images of ALS patients and individuals with specific hereditary factors linked to the disease.

- Our new results show that there are specific changes in the hypothalamus, and that these may be linked to affected metabolism, sleep and altered emotional regulation in ALS, says Åsa Petersén.

The next step for the ALS researchers in Lund is to study these changes both in a larger body of material and in greater detail.

- We’ll be conducting more research into how the hypothalamus is affected in ALS, and investigating whether we can demonstrate a direct causal link between the specific changes in the hypothalamus and affected metabolism and possibly also impaired motor skills in connection with ALS. We hope to be able to identify new lines of attack for future treatments for ALS.

There is a clear link between metabolism and ALS, even though the underlying mechanisms are not known. One risk factor for falling ill with ALS is a slim physique, while a high BMI offers protection. Previous studies have identified that increased metabolism is linked to a faster progression of the ALS disease. But it’s also been noted that in addition to muscle weakness and altered metabolism, affected individuals can also have their sleep affected and poorer emotional regulation,” says Åsa Petersén.

In the published study, the researchers show for the first time that the number of nerve cells that produce the substances orexin and oxytocin is reduced in brain tissue from ALS patients compared to control tissue. These substances regulate metabolism, sleep and emotions from the brain’s hormone centre, the hypothalamus, and may be involved in the course of the disease in connection with ALS.  Illustration: Sanaz Gabery

Research has shown that ALS is part of a spectrum of diseases that also include frontal lobe dementia, and that one common denominator is the way neurons are attacked by the protein TDP-43 (TAR DNA-binding protein 43). This is a protein that has important functions in nerve cells that regulate genes expression and how substances are transported inside the cells. It is not yet fully understood how TDP-43 causes these neurodegenerative diseases.  

Collaboration with Australia

Metabolism, sleep and emotional regulation are controlled by the brain's hormone centre, the hypothalamus. Petersén’s research group has a successful collaboration going back many years with the Faculty of Medicine’s new honorary doctor, Professor Glenda Halliday from the University of Sydney. Halliday is an internationally leading authority in the field of neurodegenerative diseases. In studies already published, this collaboration has identified disease changes in the hypothalamus specifically in frontal lobe dementia and in Huntington’s disease, another neurodegenerative disease.

Sanaz Gabery, a postdoctoral student funded by the Swedish Brain Foundation and a prospective doctor, has conducted the analyses of brain tissue from ALS patients that led the researchers to the new hypothesis about the role of the hypothalamus in ALS. “Our hypothesis was that the hypothalamus is also affected in ALS, and that specific nerve cell groups that control metabolism, sleep and emotional regulation are damaged.

The studies were conducted in Petersén’s laboratory in Lund on brain tissue from deceased ALS patients in Sydney and on healthy control tissue. The studies were made possible thanks to unique and very systematically collected clinical material from the research environment and brain banks in Australia that Professor Glenda Halliday has worked to build up over many years. One of the lead authors, Dr Rebekah Ahmed, a neurologist, has collected clinical data from these individuals at the ALS clinic in Sydney, where she works.

- Our results show that the hypothalamus is smaller in patients with ALS and that nerve cell groups that manufacture substances that regulate metabolism, sleep and emotions are damaged. These substances are orexin and oxytocin. These particular nerve cells also affected by accumulations of a protein associated with the disease called TDP-43, says Sanaz Gabery.

Wants to identify new lines of attack

In another international collaboration, Åsa Petersén has shown that the hypothalamus is smaller on MRI images of ALS patients and individuals with specific hereditary factors linked to the disease.

- Our new results show that there are specific changes in the hypothalamus, and that these may be linked to affected metabolism, sleep and altered emotional regulation in ALS, says Åsa Petersén.

The next step for the ALS researchers in Lund is to study these changes both in a larger body of material and in greater detail.

- We’ll be conducting more research into how the hypothalamus is affected in ALS, and investigating whether we can demonstrate a direct causal link between the specific changes in the hypothalamus and affected metabolism and possibly also impaired motor skills in connection with ALS. We hope to be able to identify new lines of attack for future treatments for ALS.