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Cutting-edge drugs show promise against Alzheimer's, Parkinson's, and Type 2 diabetes

Purdue University researchers have made significant strides in the battle against Alzheimer's disease, Parkinson's disease, and Type 2 diabetes.
Purdue University researchers have made significant strides in the battle against Alzheimer's disease, Parkinson's disease, and Type 2 diabetes. (CREDIT: Creative Commons)


Purdue University researchers have made significant strides in the battle against Alzheimer's disease, Parkinson's disease, and Type 2 diabetes. They have developed a range of patent-pending compounds that show promise in inhibiting protein aggregation associated with these debilitating diseases.


Alarming statistics highlight the urgency of finding effective treatments. As of 2020, approximately 38 million Americans were living with diabetes, with Type 2 diabetes accounting for up to 95% of cases. Alzheimer's disease affected as many as 5.8 million Americans, while nearly 1 million were grappling with Parkinson's disease. These numbers underscore the critical need for breakthroughs in medical science.


 
 

At the forefront of this research is Jessica Sonia Fortin, an assistant professor of basic medical sciences, physiology, and pharmacology in Purdue University's College of Veterinary Medicine. She also plays a pivotal role in the Purdue Institute for Drug Discovery.


Human Islet amyloid polypeptide (hIAPP) and type 2 diabetes mellitus (T2DM)
Human Islet amyloid polypeptide (hIAPP) and type 2 diabetes mellitus (T2DM). (CREDIT: BioRender)


Fortin leads a team of dedicated scientists focused on developing new small-molecule compounds and validating their potential through in vitro studies. Their primary goal is to prevent the aggregation of specific proteins linked to these diseases.


 
 

To support this groundbreaking research, Fortin has received funding from various sources, including the EveryCat Health Foundation, the Pharmaceutical Research and Manufacturers of America, and the National Institute on Aging, a division of the National Institutes of Health.


The central theme connecting Alzheimer's, Parkinson's, and Type 2 diabetes is protein aggregation. These diseases often manifest with symptoms such as cognitive decline, movement disorders, and, in severe cases, premature death. The common denominator in their development is the accumulation of proteins, including certain hormones.


 

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In Type 2 diabetes, for example, about 70% of cases involve a hormone called islet amyloid polypeptide (IAPP) accumulating in the pancreas. Similarly, Alzheimer's disease and Parkinson's disease are characterized by protein clumps forming in specific regions of the brain, caused by tau and alpha-synuclein proteins, respectively. Moreover, some forms of dementia display the presence of both tau and alpha-synuclein aggregates, revealing a complex interconnection between Type 2 diabetes and neurodegenerative diseases.


Existing treatments primarily focus on symptom management, leaving the root causes unaddressed. Fortin and her team, however, are taking a different approach. They aim to develop small-molecule therapeutics that not only prevent protein aggregation but also disassemble existing clumps. This dual-action strategy not only aids in the body's elimination of these byproducts but also reduces the risk of clump redistribution, which could lead to intracranial hemorrhage in the brain.


 
 

Fortin's team has synthesized a library of small-molecule compounds with similar chemical structures, specifically designed to target Alzheimer's and Parkinson's diseases. These compounds have shown significant potential in inhibiting protein aggregation at the microscale level, indicating their effectiveness.


Human Islet amyloid polypeptide (hIAPP) and loss of β cells.
Human Islet amyloid polypeptide (hIAPP) and loss of β cells. (CREDIT: BioRender)


Two compounds, in particular, have demonstrated the ability to inhibit the formation of oligomers, which are polymers with relatively few repeating units. Importantly, these compounds can cross the blood-brain barrier, reaching the brain in rodent models, a crucial advancement in the field. By preventing the formation of inclusions caused by alpha-synuclein aggregation, these compounds offer a promising avenue for treatment.


 
 

Fortin and her colleagues are actively seeking funding to delve deeper into the mechanisms of action of these small-molecule compounds, paving the way for more comprehensive research.


Beyond Alzheimer's and Parkinson's, Fortin's team is also exploring potential treatments for Type 2 diabetes. They have identified three small-molecule compounds that inhibit the formation of IAPP aggregates in the pancreas, a hallmark of the disease. These compounds have shown promising results in reducing IAPP aggregation, offering hope for improved treatments for both human and feline diabetes.


The road ahead for Fortin and her team involves further development of these treatments, conducting proof-of-concept studies, optimizing compound effects, and investigating their pharmacokinetics and pharmacodynamics. Preliminary data already indicate the presence of these compounds in the brain after injection in mice, providing valuable insights for future research.


 
 

As we look to the future, the research led by Purdue University holds immense potential for transforming the landscape of Alzheimer's, Parkinson's, and Type 2 diabetes treatments, offering hope to millions of individuals affected by these devastating diseases.



Who has Alzheimer’s Disease?


  • In 2020, as many as 5.8 million Americans were living with Alzheimer’s disease.

  • Younger people may get Alzheimer’s disease, but it is less common.

  • The number of people living with the disease doubles every 5 years beyond age 65.

  • This number is projected to nearly triple to 14 million people by 2060.

  • Symptoms of the disease can first appear after age 60, and the risk increases with age.


 
 

What is known about Alzheimer’s Disease?


Scientists do not yet fully understand what causes Alzheimer’s disease. There likely is not a single cause but rather several factors that can affect each person differently.


  • Age is the best known risk factor for Alzheimer’s disease.

  • Family history—researchers believe that genetics may play a role in developing Alzheimer’s disease. However, genes do not equal destiny. A healthy lifestyle may help reduce your risk of developing Alzheimer’s disease. Two large, long term studies indicate that adequate physical activity, a nutritious diet, limited alcohol consumption, and not smoking may help people.

  • Changes in the brain can begin years before the first symptoms appear.

  • Researchers are studying whether education, diet, and environment play a role in developing Alzheimer’s disease.

  • There is growing scientific evidence that healthy behaviors, which have been shown to prevent cancer, diabetes, and heart disease, may also reduce risk for subjective cognitive decline.


 
 

What is the burden of Alzheimer’s disease in the United States?


  • Alzheimer’s disease is one of the top 10 leading causes of death in the United States.

  • The 6th leading cause of death among US adults.

  • The 5th leading cause of death among adults aged 65 years or older.

  • In 2020, an estimated 5.8 million Americans aged 65 years or older had Alzheimer’s disease. This number is projected to nearly triple to 14 million people by 2060.


In 2010, the costs of treating Alzheimer’s disease were projected to fall between $159 and $215 billion. By 2040, these costs are projected to jump to between $379 and more than $500 billion annually.


Death rates for Alzheimer’s disease are increasing, unlike heart disease and cancer death rates that are on the decline.


 
 

Dementia, including Alzheimer’s disease, has been shown to be under-reported in death certificates and therefore the proportion of older people who die from Alzheimer’s may be considerably higher.







For more science news stories check out our New Discoveries section at The Brighter Side of News.


 

Note: Materials provided above by The Brighter Side of News. Content may be edited for style and length.


 
 

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