The WorldCare Wire – Summer 2023

Welcome to this edition of WorldCare’s quarterly e-newsletter, where you’ll learn how Nurse Case Managers help patients navigate the medical second opinion (MSO) journey. You’ll also learn about Alzheimer’s disease and research insights from WorldCare Consortium® providers.

For Your Health: Nurse Case Managers Help You Navigate the MSO Process

An MSO can ensure your diagnosis is correct and your treatment plan is the best approach possible. But where should you begin? Figuring out what records you need, who to talk to, and how to pull together an MSO request may feel intimidating.

With a WorldCare MSO, a Nurse Case Manager helps you navigate the entire process. They learn about you and your unique health history, listen to your questions and concerns, and work with you to identify all the information and files needed for medical review by specialist teams within the WorldCare Consortium®.

Our Nurse Case Managers are registered nurses with years of experience in healthcare and the MSO process. They understand medical jargon and procedures well and provide expert MSO guidance with compassion. With one of our Nurse Case Managers with you every step of the way, you can be confident that you have a trusted guide and advocate to help you navigate the process from start to finish.

Health IQ: Alzheimer’s Disease

Fast facts on Alzheimer’s disease 

Alzheimer’s disease is the most common cause of dementia. It destroys memory, the ability to think clearly, and ultimately, the ability to perform simple daily activities. Complex changes in the brain, including a loss of brain cells and their connections, begin many years before disease symptoms appear.1

Currently, experts believe Alzheimer’s disease may be caused by a combination of:1

• Age-related changes that damage brain cells, including shrinkage, inflammation, and blood vessel damage from cardiovascular disease and high blood pressure.

• Changes or differences in inherited genes since both late-onset disease in the mid-60s and the much rarer early-onset disease between age 30 and the mid-60s can be related to a person’s genes in some way.

Health and environmental factors, including heart disease, obesity, stroke, high blood pressure, diabetes, and exposure
to pollutants.

10 Alzheimer’s disease warning signs

It is true that memory changes as we age. But memory loss that affects daily life is not a normal part of aging. The following are 10 warning signs of potential Alzheimer’s disease:2

1. Memory loss that disrupts daily life: forgetting events, repeating yourself or relying on more aids to help you remember (like sticky notes or reminders).

2. Challenges in planning or solving problems: having trouble paying bills or cooking recipes you have used for years.

3. Difficulty completing familiar tasks at home, at work, or at leisure: having problems with cooking, driving places, using a cell phone, or shopping.

4. Confusion with time or place: having trouble understanding an event that is happening later, or losing track of dates.

5. Trouble understanding visual images and spatial relations: having more difficulty with balance or judging distance, tripping over things at home, or spilling or dropping things more often.

6. New problems with words in speaking or writing: having trouble following or joining a conversation or struggling to find a word you are looking for (saying “that thing on your wrist that tells time” instead of “watch”).

7. Misplacing things and losing the ability to retrace steps: placing car keys in the washer or dryer or not being able to retrace steps to find something.

8. Decreased or poor judgment: being a victim of a scam, not managing money well, paying less attention to hygiene, or having trouble taking care of a pet.

9. Withdrawing from work or social activities: not wanting to go to church or other activities as you usually do, not being able to follow football games or keep up with what’s happening.

10. Changes in mood and personality: getting easily upset in common situations or being fearful or suspicious.

WorldCare Consortium® research update:

A new treatment target and a promising
gene therapy approach for patients with neurodegenerative disorders

The protein TDP-43 is normally found in the nucleus of neurons, where DNA is located. But in almost all patients with amyotrophic lateral sclerosis (ALS) and up to half of patients with Alzheimer’s disease and frontotemporal dementia, TDP-43 is located in the cytoplasm of neurons, outside of the nucleus.

A team, including researchers at Massachusetts General Hospital, recently discovered that the loss of TDP-43 in the nucleus resulted in a dramatic decrease of stathmin-2 protein in neurons, which is essential for repairing brain cells after injury and maintaining neuromuscular junctions, the locations where motor neurons connect to muscle fibers.

Next, the researchers designed an investigational gene therapy known as an antisense oligonucleotide in collaboration with a pharmaceutical company. The gene therapy successfully boosted normal stathmin-2 protein levels and suppressed the production of abnormal stathmin-2 in TDP-43-deficient human neurons and mouse models. Published recently in Science, these findings suggest that gene therapy is a promising approach for developing new treatments for neurodegenerative disorders with
TDP-43 deficiency.

New treatment options for
Alzheimer’s disease

While there is no cure for Alzheimer’s, it’s crucial to speak to a healthcare provider as soon as possible if you have memory problems. The U.S. Food and Drug Administration recently approved new treatment options that work best for people with early or middle-stage Alzheimer’s disease.3 The FDA may soon approve another drug based on promising clinical trial results.4

1 What is Alzheimer’s Disease? Accessed at

2 Alzheimer’s Disease and Healthy Aging. 10 Warning Signs of Alzheimer’s. Accessed at

3 National Institute of Aging. Health Topics A-Z. How is Alzheimer’s Disease Treated? Accessed at

4 News release: May 3, 2023. Lilly’s Donanemab Significantly Slowed Cognitive and Functional Decline in Phase 3 Study of Early Alzheimer’s Disease. Accessed at

WorldCare Consortium® Provider Research News

Researchers identify and target an unexpected weakness in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is an aggressive and difficult-to-treat breast cancer subtype. Most TNBC and half of all cancers have a mutation in the p53 gene, which normally functions as a tumor suppressor. Cancer cells can be wily: they can increase levels of a protein called MDM2 to keep levels of p53 protein in check, allowing them to grow and survive.

Drugs called MDM2 inhibitors that block MDM2 allow p53 to activate and control some p53-deficient cancers, but they have not been effective in treating p53-deficient TNBC. Now, researchers at Jefferson Health’s Sidney Kimmel Cancer Center are the first to identify that deleting the MDM2 gene caused p53-deficient cancer cells to die in mouse models.

They also developed an experimental compound called a proteolysis-targeting chimera (PROTAC) to address this new target. The PROTAC eliminated MDM2 protein from cancer cells in mouse models and lab studies of human TNBC. Their ground-breaking results, published in Cancer Discovery, represent an exciting new approach for treating TNBC and other
p53-deficient cancers.

Fast Facts on Clinical Trials

You hear a lot about clinical trials, but do you really know what they are?

Clinical trials study new drugs or drug combinations, surgical approaches, medical devices, or ways to improve the quality of life of people living with illnesses. The goal is to see whether the new intervention is safe and effective. Many WorldCare Consortium® providers conduct clinical trials.

There are typically three phases of clinical research:5

• Phase 1 trials:
Study a new drug or treatment in a small group of people (20-80) for the first time to learn about safety and side effects.

• Phase 2 trials:
Study a new drug or treatment in a larger group of people (100-300) to determine effectiveness and study safety further.

• Phase 3 trials:
Study a new drug or treatment in a significantly larger group of people (1,000-3,000) to confirm effectiveness, monitor side effects, and compare it with standard treatments.

Individuals who volunteer to participate in clinical trials provide informed consent after thorough discussions with research teams about what’s involved, including the study’s goal and duration, the treatments, and the potential risks and benefits.

Without clinical research, we would not have access to essential medications and treatment approaches that have saved lives and significantly improved outcomes for people with serious diseases.

5 National Institutes of Health. NIH Clinical Trials and You: The Basics. Accessed at