By KELLY CARROLL

There is a dire need to raise awareness about heart disease in women. It is the number one killer of American women, and key data points reveal a lack of cognizance among doctors and women.

An assessment of primary care physicians published in 2019 revealed that only 22% felt extremely well prepared to evaluate cardiovascular disease risks in female patients. A 2019 survey of American women showed that just 44% recognized heart disease as the number one cause of death in women. Ten years earlier, in 2009, the same survey found that 65% of American women recognized heart disease as the leading cause of female death, revealing an alarming decline in awareness. 

Recent evidence suggests that many adults don’t know the important health numbers that can help identify heart disease risk factors, like their blood sugar and cholesterol. A 2024 survey of American adults conducted by The Ohio State University Wexner Medical Center found that only 35% of adults knew their blood pressure and 16% of adults knew their cholesterol levels. In comparison, the study reported that 58% knew their childhood friend’s birthday.

Heart Disease Risk Factors in Women

Women have specific risk factors for heart disease that don’t pertain to men. Nanette Wenger, M.D., a cardiologist and researcher, said in an American Heart Association (AHA) statement, “For most of the last century, heart disease was considered a problem for men, and women were believed to have cardioprotective benefits from female sex hormones such as estrogen. However, emerging evidence shows that there are a substantial number of heart disease risk factors that are specific to women or predominant in women.” Some gender-specific risk factors outlined by the AHA are early onset of menstruation, early menopause, autoimmune disease, anxiety, depression, and pregnancy complications.

Bethany Barone Gibbs, Ph.D., an associate professor at West Virginia University, emphasized in an email that pregnancy is a “critical window” for women’s cardiovascular health. She said, “The cardiovascular and metabolic challenge of pregnancy may unmask risk for conditions like hypertension and diabetes, but it is also possible (though not yet clear) that experiencing an adverse pregnancy outcome may independently contribute to the development of maternal cardiovascular disease.” A history of adverse pregnancy outcomes can be associated with more than two times the risk of cardiovascular disease later in life, she explained. 

Filling in knowledge gaps regarding the connections between pregnancy and long-term cardiovascular health is important to improving outcomes.

One knowledge gap is effective strategies to reduce future cardiovascular disease risk among people who experience adverse pregnancy outcomes. “Though we know these individuals are at much higher risk for poor outcomes, evidence-based approaches that are tailored to the postpartum years (which often includes subsequent pregnancies) are lacking,” Gibbs said. 

Gibbs is working to identify the optimal physical activity, sedentary behavior, and sleep patterns during the postpartum years that may reduce cardiovascular risk. “We are hopeful that we can identify which behaviors are most important for cardiovascular recovery following pregnancy and we can work with these populations to prioritize the most potent interventions to support heart health during the postpartum period,” she said. 

Signs of Heart Disease in Women

Knowing the signs of heart disease in women is an important part of saving lives. Men and women both commonly experience chest pain during a heart attack, but women are more likely than men to have other symptoms unrelated to chest pain. These symptoms include shortness of breath, nausea, vomiting, perspiration, indigestion, atypical fatigue, faintness and pain in the torso, neck, jaw, shoulders and arms.

A February 2020 study reported that women under age 55 display different heart attack symptoms and a wider variety of symptom combinations than men. The study’s lead author, John Brush, Jr., M.D., said in an AHA statement, “As a physician, if you’re looking at a woman, you need to think more expansively. She might not have the prototypical combination of features of chest pain, radiating pain down the arm, shortness of breath and sweating, which are often the examples given in textbooks.” 

It is also common for women to attribute their heart disease symptoms to another ailment, such as the flu, acid reflux or aging. Failure to recognize the symptoms of heart disease can cause women to delay seeking treatment. While chest pain is still the most common symptom of heart disease in both men and women, awareness of other heart disease symptoms can help women get treatment faster.

Heart Disease Prevention

Most heart disease cases are preventable. Wenger said in an AHA statement, “About 80-90% of cardiovascular disease is preventable. Implementing preventative strategies early could have a significant impact on reducing premature cardiovascular disease, stroke and related mortality for women.”

Lifestyle choices like maintaining a healthy diet and prioritizing physical activity can help prevent heart disease. Keeping a healthy weight and steering clear of tobacco products also support cardiovascular health. A person understanding her individual risks of heart disease and factors that may put her at higher risk, such as high blood pressure and diabetes, is also helpful. The AHA has outlined the top 8 factors for cardiovascular health, called Life’s Essential 8. They are: Eat Better, Be More Active, Quit Tobacco, Get Healthy Sleep, Manage Weight, Control Cholesterol, Manage Blood Sugar, and Manage Blood Pressure. 

Efforts to Raise Awareness and Understanding

National efforts are being made to raise awareness of heart disease in women. The AHA hosts the Go Red for Women campaign to fight cardiovascular disease in women. Circulation published the eighth yearly Go Red for Women issue featuring new cardiovascular research in women in 2024. The National Heart, Lung and Blood Institute also hosts a cardiovascular health education program called The Heart Truth. 

While these efforts are underway to improve heart disease outcomes for women, women need more. AHA laid out a constellation of strategies to improve women’s heart health in a May 2022 publication, and several deserve further emphasis here. To make progress, we need more and improved gender-specific cardiovascular disease training for healthcare providers. We need more collaboration between cardiologists, obstetricians-gynecologists, primary care physicians and other healthcare providers to improve the prevention and treatment of cardiovascular disease in women. We need more research on gender-specific cardiovascular disease to fill in knowledge gaps and improve prevention and treatment strategies. 

We also need more awareness. Spreading awareness of the risk factors and symptoms of heart disease in women can help save lives. Campaigns can help spread this message, and men and women sharing this information with other men and women can also help. If we all know the risk factors and symptoms of heart disease in women, all our mothers, sisters, daughters, neighbors and friends will be better off. 

More than 300,000 women in the U.S. died from heart disease in 2021. Let’s make sure that number is much lower in 2031 and beyond. 

Kelly Carroll is a freelance health writer based in Kentucky. More at her site

By STEVEN ZECOLA

This study tracks the decades-long journey to harness alpha-synuclein as a treatment for Parkinson’s disease. Steven Zecola an activist who tracks Parkinson’s research and was on THCB last month discussing it, offers three key changes needed to overcome the underlying challenges.

A Quick Start for Alpha-Synuclein R&D

In the mid-1990’s, Parkinson’s patient advocacy groups had become impatient by the absence of any major therapeutic advances in the 25 years since L-dopa had been approved for Parkinson’s disease (PD).

The Director of National Institute of Neurological Disorders and Stroke (NINDS) set up a workshop in August 1995 that featured scientists with expertise in human genetics who might open novel avenues for PD research.

One such scientist, Robert Nussbaum, made the following remarks at the workshop:

“…finding genes responsible for familial Parkinson’s should be helpful for understanding all forms of the disease. Techniques now available should allow researchers to find the genes responsible for familial Parkinson’s disease in a relatively short time.”

Two years later in 1997, Spillantini et al. showed that alpha-synuclein (A-syn) was a major contributor of abnormal clusters of proteins in the brain, not only in patients with synuclein mutations but, more importantly, in patients with sporadic Parkinson’s disease as well.

As Nussbaum had predicted, progress had occurred rapidly. President Clinton in his 1998 State of the Union address, said:

“Think about this, the entire store of human knowledge now doubles every 5 years. In the 1980’s, scientists identified the gene causing cystic fibrosis. It took 9 years. Last year scientists located the gene that causes Parkinson’s disease in only 9 days.”

The NIH is Asked to Take a Leadership Role

Shortly after President Clinton’s call to action, a Senate Committee asked the National Institutes of Health (NIH) to develop a coordinated effort to take advantage of promising opportunities in PD research.

In response, the NIH and the National Institute of Neurological Disease and Stroke (NINDS) held a major planning meeting that included all components of the PD community. The group’s recommendations formed the basis of a five-year PD Research Agenda.

The Research Agenda was codified in a comprehensive 42-page report that covered all aspects of research from better understanding the disease, to creating new research capabilities, to developing new treatments, and to enhancing the research process.

Noting the “remarkable paradigm shift in Parkinson’s disease research” from the discovery of the effects of alpha-synuclein, the report stated that:

“New insights into the role of synucleins in the pathobiology of Parkinson’s disease would accelerate discovery of more effective therapies and provide fresh research opportunities to advance our understanding of Parkinson’s disease”.

NIH invested nearly $1 billion from FY 2000 to FY 2004 to implement the PD Research Agenda.  A-syn research would be funded out of the funds allocated to the categories of Genetics and Epidemiology, with both categories targeted to receive about 15% of the overall spending.

Overall, there were 19 broad categories with spending authorizations, including $32.7 million allocated to Program Management and Direction.

When the PD Research Agenda reached the end of its 5-year span, NINDS sponsored a second PD Summit which was held in June 2005.  It brought together an industry-wide consortium to assess the progress over the previous five years and to develop future directions for PD research.

The participants generated more than fifty specific recommendations.  NIH considered these plans and the unmet goals from previous efforts and developed a 3-year Plan.

A major focus of that Plan was to identify and intervene with the causes of PD.

As reiterated in the 2006 Plan:

“…Understanding the role of alpha-synuclein may enable strategies to selectively block the harmful effects associated with this protein as a novel approach to treatment of PD”.

NINDS noted that:

“While PD is not a rare or orphan disease, other more prevalent diseases such as stroke, obesity and diabetes offer considerably larger “markets” for drug therapies than does PD. Thus, pharmaceutical companies have primarily focused on medicinal chemistry and alterations of existing PD or other neurological drugs (e.g., dopamine agonists) rather than investing in new drugs.”

In essence, NINDS recognized the financial conundrum of drug development for A-syn and other PD therapies, but looked to academia to solve the problem through its grant program.

Lacking success from the efforts of the 2006 Plan, NINDS organized another conference in January 2014 called: Parkinson’s Disease 2014: Advancing Research, Improving Lives. The purpose of this initiative was to identify significant challenges and to highlight the highest priorities for advancing research.

Thirty-one recommendations were provided. The summary of the conference included the Top 3 priorities for clinical research, translational research, and basic research. Under basic research, priorities 1 and 2 related to alpha-synuclein.

Given that the work specified for A-syn research was still at an early stage of basic research in 2014, it is clear that a large gap existed between the previous NINDS priorities for A-syn and what was delivered.

Private Interests Finally Move Forward with Alpha-Synuclein

Recognizing the continuing lack of progress and the need for funding, the Michael J. Fox Foundation announced a $10-million “Ken Griffin Alpha-synuclein Imaging Competition” in 2019 to spur development of a critical and elusive imaging research tool for Parkinson’s disease.

In March 2023, MJFF announced that the three initial Alpha-synuclein imaging competition teams — AC Immune, Mass General Brigham and Merck— made tremendous advancements in the development of different alpha-synuclein tracer methods.

MJFF awarded Merck an additional $1.5 million to continue the work and bring its tool to life. The first-in-human clinical trial of its alpha-synuclein PET tracer began in 2023. 

Additionally, after more than two decades of basic research, five private research companies filed applications with the FDA and have initiated early-stage PD trials.

• Neuropore Therapies and UCB are collaborating on an oral small molecule, which aims to prevent the formation of alpha-synuclein clusters.
• Prothena Biosciences, in conjunction with Roche, is testing a humanized anti-alpha-synuclein antibody.
• Biogen is investigating another monoclonal antibody against alpha-synuclein.
• AFFiRiS, an Austrian biotech company, is testing an alpha-synuclein vaccine. AC Immune has recently announced the acquisition of all of AFFiRiS’ assets and underlying intellectual property related to its vaccine candidates targeting a-syn.
• Vaxxinity uses an immunotherapy candidate codenamed UB–312 to target toxic forms of aggregated α-synuclein in the brain to fight Parkinson’s. Its Chairman recently said that: “Our findings suggest UB-312 could transform Parkinson’s care, offering hope for improved outcomes with a disease-modifying treatment”.

As with all R&D projects, there are many remaining challenges in the development of A-syn therapies before reaching the market. Nevertheless, assuming that at least one of the five on-going trials will be successful, we can expect a therapy utilizing A-syn will be approved by the FDA within the next 5-8 years. The net effect is that the overall development window between A-syn’s discovery in 1997 and its application to patients would be approximately 35 years – assuming that the research goes relatively smoothly from here.

Given its performance to date, the view from NIH regarding PD research is:

“… Our failures in bringing treatments to the goal line are due to remaining large gaps in knowledge of the underlying biology that causes and drives the disease. As we fill in these gaps, the chances of success will increase. Some of the gaps we know about, others we only find out about when the science opens another door”.

Why Has This Research Taken So Long?

With the benefit of hindsight, we can point to two areas that accounted for the greatest obstacles to progress – focus and resources.

In reading the PD research plans and reports from 2000, 2006 and 2014, it appears that NINDS threw everything it knew about PD into the hopper. There were hundreds of recommendations, projects and so-called priorities. But a key factor of success in research is having a team of motivated scientists with the necessary skills, knowledge and thinking ability to solve a finely-honed question.

There simply are not enough great minds to track down all of the “to do’s” in the three NINDS PD research plans.  Also, communications and networking are important components of scientific advancement, yet the capability to network with the widespread participation in the small grants program was lacking.

The implication of using the term “focus” is that it comes with the assignment of responsibility and accountability if the priority doesn’t get done. There appears to be little outside oversight of the efficiency and effectiveness of the research dollars that were utilized on A-syn or other PD research projects. If anything, NIH seems content with the output.

Finally, NIH/NINDS knew there was a funding problem in crossing the Valley of Death from basic research to clinical trials, but these organizations fell back to their comfort zone, namely small grants to academicians. This strategy did not produce the necessary results.

A Better Approach

In 1998 and thereafter, alpha-synuclein needed a swat team of top-flight researchers along with a commitment for additional funds as the project progressed out of basic research and through the requisite clinical trials.

To address the shortcomings to date, the Department of Health and Human Services (HHS) should step in and 1) narrow the PD research priority list to the top candidates, 2) require the establishment of a robust communications network for sharing information and 3) relax the FDA regulations for PD to help level the fund-raising playing field.

In particular, HHS/NIH/NINDS must recognize that investments in new healthcare therapies such as A-syn come with very high risks and those risky investment dollars get to choose between healthcare therapies that go through 15+ years of basic research and expensive clinical trials and other opportunities that can be launched in less than a year.

Of paramount concern, the FDA’s regulatory scheme has had two deleterious effects on fund-raising. First, the FDA overhang has dried up interest in angel and venture capital investing in potential therapies such as A-syn. The result has been a Valley of Death between basic research and drug development. Second, even if the initial Valley can be crossed through government grants or non-profit donations, the FDA regulatory scheme puts an enormous burden on companies to raise scores of millions of dollars for lengthy clinical trials that face an uncertain regulatory outcome.

NIH/NINDS have not recognized that even without any direct role in fundraising, the FDA dominates the fund-raising process. For example, approximately 90% of fundraising for R&D is based on claims tied to regulatory milestones. Investors are well-aware of the challenges of the FDA approval process and it curbs investor interest.

Even in basic research, the FDA has had a large influence on scientific progress. For the academic entrepreneur, early development of an effective regulatory plan can be the difference between success and failure. Therefore, regulatory strategy becomes a critical component of the innovation process.

HHS must also recognize that the FDA has safety-first culture and a not-invented-here syndrome when it comes to any proposed changes to its processes.

The solution to these challenges, in part, entails HHS imposing a relaxed regulatory scheme for PD. For example, the FDA should be excludedfrom Phase 1 and Phase 2 trials and from providing any guidance to researchers prior to Phase 3 clinical trials. Such a change will speed development, unleash innovation, and improve early-stage fund-raising.

Second, to improve performance of the research endeavors, NINDS should be tasked to develop and manage a formal, hub-and-spoke, communications network among all stakeholders involved in PD research. ClinicalTrials.gov does not satisfy this requirement because it contains misleading information.

Facilitating regular exchanges of information, data sharing, and collaboration should help to maximize the impact of research efforts and avoid duplication of work. For the investment community, a partition in the hub with investment-related information would help to build a bridge over the Valley of Death and bring more funding to potential therapies such alpha-synuclein.

This investor-related partition of the communications office should generally be housed by MBAs (rather than by Ph.D.’s) who are focused on communicating high value research endeavors with the not-so-subtle intent of fomenting an interest in investments. NIH should consider hiring an investment banking firm to assist in setting up the investor-related component of this information network.

The third recommendation for change is that NIH should convene a very small group of experts working on PD research to identify the three most-likely-to-succeed paths to a cure. It should ensure that those paths have adequate personnel and sufficient research dollars for completion.  Progress should be monitored on a regular basis.

Lastly, I should mention that the Michael J. Fox Foundation has done an excellent job on a number of important issues and should be a major part of any restructure going forward. For example, HHS could outsource the communications hub to MJFF.

The bottom line is that all components of the PD industry, including the FDA, must be on the same page in terms of finding a cure for PD within a reasonable amount of time given existing resources whether it be with alpha synuclein or other therapies. Such has not been the case with A-syn to date, and similarly, we have witnessed that the entire research effort for PD has underperformed – and will continue to underperform – in the absence of corrective action.

The Long and Tortured History of Alpha-Synuclein and Parkinson’s Disease

Preface

This study tracks the decades-long journey to harness alpha-synuclein as a treatment for Parkinson’s disease. The author offers three key changes needed to overcome the underlying challenges.

A Quick Start for Alpha-Synuclein R&D

In the mid-1990’s, Parkinson’s patient advocacy groups had become impatient by the absence of any major therapeutic advances in the 25 years since L-dopa had been approved for Parkinson’s disease (PD).

The Director of National Institute of Neurological Disorders and Stroke (NINDS) set up a workshop in August 1995 that featured scientists with expertise in human genetics who might open novel avenues for PD research.

One such scientist, Robert Nussbaum, made the following remarks at the workshop:

“…finding genes responsible for familial Parkinson’s should be helpful for understanding all forms of the disease. Techniques now available should allow researchers to find the genes responsible for familial Parkinson’s disease in a relatively short time.”

Two years later in 1997, Spillantini et al. showed that alpha-synuclein (A-syn) was a major contributor of abnormal clusters of proteins in the brain, not only in patients with synuclein mutations but, more importantly, in patients with sporadic Parkinson’s disease as well.

As Nussbaum had predicted, progress had occurred rapidly. President Clinton in his 1998 State of the Union address, said:

“Think about this, the entire store of human knowledge now doubles every 5 years. In the 1980’s, scientists identified the gene causing cystic fibrosis. It took 9 years. Last year scientists located the gene that causes Parkinson’s disease in only 9 days.”

The NIH is Asked to Take a Leadership Role

Shortly after President Clinton’s call to action, a Senate Committee asked the National Institutes of Health (NIH) to develop a coordinated effort to take advantage of promising opportunities in PD research.

In response, the NIH and the National Institute of Neurological Disease and Stroke (NINDS) held a major planning meeting that included all components of the PD community. The group’s recommendations formed the basis of a five-year PD Research Agenda.

The Research Agenda was codified in a comprehensive 42-page report that covered all aspects of research from better understanding the disease, to creating new research capabilities, to developing new treatments, and to enhancing the research process.

Noting the “remarkable paradigm shift in Parkinson’s disease research” from the discovery of the effects of alpha-synuclein, the report stated that:

“New insights into the role of synucleins in the pathobiology of Parkinson’s disease would accelerate discovery of more effective therapies and provide fresh research opportunities to advance our understanding of Parkinson’s disease”.

NIH invested nearly $1 billion from FY 2000 to FY 2004 to implement the PD Research Agenda.  A-syn research would be funded out of the funds allocated to the categories of Genetics and Epidemiology, with both categories targeted to receive about 15% of the overall spending.

Overall, there were 19 broad categories with spending authorizations, including $32.7 million allocated to Program Management and Direction.

When the PD Research Agenda reached the end of its 5-year span, NINDS sponsored a second PD Summit which was held in June 2005.  It brought together an industry-wide consortium to assess the progress over the previous five years and to develop future directions for PD research.

The participants generated more than fifty specific recommendations.  NIH considered these plans and the unmet goals from previous efforts and developed a 3-year Plan.

A major focus of that Plan was to identify and intervene with the causes of PD. As reiterated in the 2006 Plan:

“…Understanding the role of alpha-synuclein may enable strategies to selectively block the harmful effects associated with this protein as a novel approach to treatment of PD”.

NINDS noted that:

“While PD is not a rare or orphan disease, other more prevalent diseases such as stroke, obesity and diabetes offer considerably larger “markets” for drug therapies than does PD. Thus, pharmaceutical companies have primarily focused on medicinal chemistry and alterations of existing PD or other neurological drugs (e.g., dopamine agonists) rather than investing in new drugs.”

In essence, NINDS recognized the financial conundrum of drug development for A-syn and other PD therapies, but looked to academia to solve the problem through its grant program.

Lacking success from the efforts of the 2006 Plan, NINDS organized another conference in January 2014 called: Parkinson’s Disease 2014: Advancing Research, Improving Lives. The purpose of this initiative was to identify significant challenges and to highlight the highest priorities for advancing research.

Thirty-one recommendations were provided. The summary of the conference included the Top 3 priorities for clinical research, translational research, and basic research. Under basic research, priorities 1 and 2 related to alpha-synuclein.

Given that the work specified for A-syn research was still at an early stage of basic research in 2014, it is clear that a large gap existed between the previous NINDS priorities for A-syn and what was delivered.

Private Interests Finally Move Forward with Alpha-Synuclein

Recognizing the continuing lack of progress and the need for funding, the Michael J. Fox Foundation announced a $10-million “Ken Griffin Alpha-synuclein Imaging Competition” in 2019 to spur development of a critical and elusive imaging research tool for Parkinson’s disease.

In March 2023, MJFF announced that the three initial Alpha-synuclein imaging competition teams — AC Immune, Mass General Brigham and Merck— made tremendous advancements in the development of different alpha-synuclein tracer methods.

MJFF awarded Merck an additional $1.5 million to continue the work and bring its tool to life. The first-in-human clinical trial of its alpha-synuclein PET tracer began in 2023. 

Additionally, after more than two decades of basic research, five private research companies filed applications with the FDA and have initiated early-stage PD trials.

• Neuropore Therapies and UCB are collaborating on an oral small molecule, which aims to prevent the formation of alpha-synuclein clusters.
• Prothena Biosciences, in conjunction with Roche, is testing a humanized anti-alpha-synuclein antibody.
• Biogen is investigating another monoclonal antibody against alpha-synuclein.
• AFFiRiS, an Austrian biotech company, is testing an alpha-synuclein vaccine. AC Immune has recently announced the acquisition of all of AFFiRiS’ assets and underlying intellectual property related to its vaccine candidates targeting a-syn.
• Vaxxinity uses an immunotherapy candidate codenamed UB–312 to target toxic forms of aggregated α-synuclein in the brain to fight Parkinson’s. Its Chairman recently said that: “Our findings suggest UB-312 could transform Parkinson’s care, offering hope for improved outcomes with a disease-modifying treatment”.

As with all R&D projects, there are many remaining challenges in the development of A-syn therapies before reaching the market. Nevertheless, assuming that at least one of the five on-going trials will be successful, we can expect a therapy utilizing A-syn will be approved by the FDA within the next 5-8 years. The net effect is that the overall development window between A-syn’s discovery in 1997 and its application to patients would be approximately 35 years – assuming that the research goes relatively smoothly from here.

Given its performance to date, the view from NIH regarding PD research is:

“… Our failures in bringing treatments to the goal line are due to remaining large gaps in knowledge of the underlying biology that causes and drives the disease. As we fill in these gaps, the chances of success will increase. Some of the gaps we know about, others we only find out about when the science opens another door”.

Why Has This Research Taken So Long?

With the benefit of hindsight, we can point to two areas that accounted for the greatest obstacles to progress – focus and resources.

In reading the PD research plans and reports from 2000, 2006 and 2014, it appears that NINDS threw everything it knew about PD into the hopper. There were hundreds of recommendations, projects and so-called priorities. But a key factor of success in research is having a team of motivated scientists with the necessary skills, knowledge and thinking ability to solve a finely-honed question.

There simply are not enough great minds to track down all of the “to do’s” in the three NINDS PD research plans.  Also, communications and networking are important components of scientific advancement, yet the capability to network with the widespread participation in the small grants program was lacking.

The implication of using the term “focus” is that it comes with the assignment of responsibility and accountability if the priority doesn’t get done. There appears to be little outside oversight of the efficiency and effectiveness of the research dollars that were utilized on A-syn or other PD research projects. If anything, NIH seems content with the output.

Finally, NIH/NINDS knew there was a funding problem in crossing the Valley of Death from basic research to clinical trials, but these organizations fell back to their comfort zone, namely small grants to academicians. This strategy did not produce the necessary results.

A Better Approach

In 1998 and thereafter, alpha-synuclein needed a swat team of top-flight researchers along with a commitment for additional funds as the project progressed out of basic research and through the requisite clinical trials.

To address the shortcomings to date, the Department of Health and Human Services (HHS) should step in and 1) narrow the PD research priority list to the top candidates, 2) require the establishment of a robust communications network for sharing information and 3) relax the FDA regulations for PD to help level the fund-raising playing field.

In particular, HHS/NIH/NINDS must recognize that investments in new healthcare therapies such as A-syn come with very high risks and those risky investment dollars get to choose between healthcare therapies that go through 15+ years of basic research and expensive clinical trials and other opportunities that can be launched in less than a year.

Of paramount concern, the FDA’s regulatory scheme has had two deleterious effects on fund-raising. First, the FDA overhang has dried up interest in angel and venture capital investing in potential therapies such as A-syn. The result has been a Valley of Death between basic research and drug development. Second, even if the initial Valley can be crossed through government grants or non-profit donations, the FDA regulatory scheme puts an enormous burden on companies to raise scores of millions of dollars for lengthy clinical trials that face an uncertain regulatory outcome.

NIH/NINDS have not recognized that even without any direct role in fundraising, the FDA dominates the fund-raising process. For example, approximately 90% of fundraising for R&D is based on claims tied to regulatory milestones. Investors are well-aware of the challenges of the FDA approval process and it curbs investor interest.

Even in basic research, the FDA has had a large influence on scientific progress. For the academic entrepreneur, early development of an effective regulatory plan can be the difference between success and failure. Therefore, regulatory strategy becomes a critical component of the innovation process.

HHS must also recognize that the FDA has safety-first culture and a not-invented-here syndrome when it comes to any proposed changes to its processes.

The solution to these challenges, in part, entails HHS imposing a relaxed regulatory scheme for PD. For example, the FDA should be excludedfrom Phase 1 and Phase 2 trials and from providing any guidance to researchers prior to Phase 3 clinical trials. Such a change will speed development, unleash innovation, and improve early-stage fund-raising.

Second, to improve performance of the research endeavors, NINDS should be tasked to develop and manage a formal, hub-and-spoke, communications network among all stakeholders involved in PD research. ClinicalTrials.gov does not satisfy this requirement because it contains misleading information.

Facilitating regular exchanges of information, data sharing, and collaboration should help to maximize the impact of research efforts and avoid duplication of work. For the investment community, a partition in the hub with investment-related information would help to build a bridge over the Valley of Death and bring more funding to potential therapies such alpha-synuclein.

This investor-related partition of the communications office should generally be housed by MBAs (rather than by Ph.D.’s) who are focused on communicating high value research endeavors with the not-so-subtle intent of fomenting an interest in investments. NIH should consider hiring an investment banking firm to assist in setting up the investor-related component of this information network.

The third recommendation for change is that NIH should convene a very small group of experts working on PD research to identify the three most-likely-to-succeed paths to a cure. It should ensure that those paths have adequate personnel and sufficient research dollars for completion.  Progress should be monitored on a regular basis.

Lastly, I should mention that the Michael J. Fox Foundation has done an excellent job on a number of important issues and should be a major part of any restructure going forward. For example, HHS could outsource the communications hub to MJFF.

The bottom line is that all components of the PD industry, including the FDA, must be on the same page in terms of finding a cure for PD within a reasonable amount of time given existing resources whether it be with alpha synuclein or other therapies. Such has not been the case with A-syn to date, and similarly, we have witnessed that the entire research effort for PD has underperformed – and will continue to underperform – in the absence of corrective action.

Steve Zecola sold his web application and hosting business when he was diagnosed with Parkinson’s disease twenty three years ago.  Since then, he has run a consulting practice, taught in graduate business school, and exercised extensively

By JEFF GOLDSMITH

On Christmas Eve 2014, I received a present of some profoundly unwelcome news: a 64 slice CT scan confirming not only the presence of a malignant tumor in my neck, but also a fluid filled mass the size of a man’s finger in my chest cavity outside the lungs. Two days earlier, my ENT surgeon in Charlottesville, Paige Powers, had performed a fine needle aspiration of a suspicious almond-shaped enlarged lymph node, and the lab returned a verdict of “metastatic squamous cell carcinoma of the head and neck with an occult primary tumor”. 

I had worked in healthcare for nearly forty years when cancer struck, and considered myself an “expert” in how the health system worked. My experience fundamentally changed my view of how health care is delivered, from the patient’s point of view. Many have compared their fight against cancer as a “battle”. Mine didn’t feel like a battle so much as a chess match where the deadly opponent had begun playing many months before I was aware that he was my adversary. The remarkable image from Ingmar Bergman’s Seventh Seal sums up how this felt to me.

The CT scan was the second step in determining how many moves he had made, and in narrowing the uncertainty about my possible counter moves. The scan’s results were the darkest moment: if the mysterious fluid filled mass was the primary tumor, my options had already dangerously narrowed. Owing to holiday imaging schedules, it was not until New Years’ Eve, seven interminable days later, that a PET/CT scan dismissed the chest mass as a benign fluid-filled cyst. I would require an endoscopy to locate the still hidden primary tumor somewhere in my throat.  

I decided to seek a second opinion at my alma mater, the University of Chicago, where I did my doctoral work and subsequently worked in medical center administration.

The University of Chicago had a superb head and neck cancer team headed by Dr. Everett Vokes, Chair of Medicine, whose aggressive chemotherapy saved the life and career of Chicago’s brilliant young chef, Grant Achatz of Alinea, in 2007.

If surgery was not possible, Chicago’s cancer team had a rich and powerful repertoire of non-surgical therapies. I was very impressed both with their young team, and how collaborative their approach was to my problem. Vokes’ initial instinct that mine was a surgical case proved accurate.

The young ENT surgeon I saw there in an initial consultation, Dr. Alex Langerman performed a quick endoscopy and thought he spotted a potential primary tumor nestled up against my larynx. Alex asked me to come back for a full-blown exploration under general anaesthesia, which I did a week later. The possible threat to my voice, which could have ended my career, convinced me to return to Chicago for therapy. Alex’s endoscopy found a tumor the size of a chickpea at the base of my tongue. Surgery was scheduled a week later in the U of Chicago’s beautiful new hospital, the Center for Care and Discovery.

This surgery was performed on Feb 2, 2015, by a team of clinicians none of whom was over the age of forty. It was not minor surgery, requiring nearly six hours:  resections of both sides of my neck, including the dark almond and a host of neighboring lymph nodes. And then, there was robotic surgery that removed a nearly golf ball-sized piece of the base of my tongue and throat. The closure of this wound remodeled my throat.

I arrived in my hospital room late that day with the remarkable ability to converse in my normal voice.

Thoughtfully, I was put in a quasi-isolation unit with two doors and negative air pressure. There was a consistent, very high level of focus on infection control throughout my stay. The next day, flushed with the news that no cancer had been found in any other lymph nodes, that there were clean, ample cuts around the tumors we knew about, and, best of all, that no follow-on chemo- or radiotherapy would be needed, I chatted away happily with two visitors for almost ninety minutes. I was repaid for this premature end-zone celebration with a siege of intense throat pain that lasted over a week. I was also repaid in a different way for the optimistic removal the next morning of the nasogastric tube installed during my surgery to feed and medicate me post-op. 

My surgeon, Alex Langerman, was generous with his time. We had four visits in the hospital that I could remember and one which I couldn’t. He responded thoughtfully and substantively to my questions and concerns but delegated the day-to-day management of my care to his senior and junior residents. The senior residents, who were present in the OR,  were as impressive as Alex was.

Some of the junior residents, however, literally phoned it in. On the second night, I woke up strangling on a large blood clot that had dislodged from the wound and blocked my airway. The anxious nurse in charge of my care paged the on-call resident who . . . didn’t answer the page in 90 minutes. Paged again, the resident scolded the nurse for bothering her and instructed the nurse to inform me that “breathing and swallowing problems were normal for this type of surgery” and refused to come in to the hospital to examine me.

At this point, I asked to speak to the resident on the phone, which prompted her to appear in my room thirty minutes later. She performed a perfunctory, fifteen-second examination, pressing down on my tongue with a depressor, but failing to examine my airway where a large piece of the clot was still lodged. Then she delivered a sour little lecture on how “breathing and swallowing problems were normal. etc.” and after documenting that she had showed up, ordered a swallowing study for the next day and vanished without taking any other action, not to be seen again. I eventually coughed up the rest of the clot myself and prayed it wouldn’t happen again. 

The failure of on-call residents to respond to pages from the nurses caring for me was repeated later in my stay. Despite this inconstant clinical back up, I received thoughtful and attentive nursing care throughout my stay. Sadly, the nurses seemed to spend twice as long typing into the numerous computers in the rooms and at the nursing station as they did actually caring for us.  

However, the inadequate pain control regimen vital to my regaining my ability to swallow exacted a huge price. Originally, my pain meds were to be delivered through the nasogastric tube that bypassed my new throat. When the tube was removed the day after surgery, no thought was given to rethinking my pain control. Though I had a mild patient-controlled anaesthesia through IV, I was expected to swallow my primary pain medication delivered in liquid form roughly every four hours. 

As you might expect given the large wound in my throat, swallowing was a nightmare, particularly since the liquid pain medications seemed to be suspended in alcohol. I could not swallow them sitting up in bed, so I made a medication station out of my window sill. Even if I diluted them with water or a suspension of edible fiber, it took almost twenty minutes to down each dose of pain meds. Every tiny swallow brought a sharp stab, a hop and a yelp, followed by a spasm of painful coughing. Several days of protest brought a new idea:  bitter ground up pain pills mixed with apple sauce! Chunks of pain medication and apple hung up in my throat, lodging on the wound. 

Then the hospital entered the fugue state otherwise known as the weekend. A hospital stay expected to be seventy-two hours had stretched to six days, during which I was unable to eat and barely able to swallow even water, let alone therapeutic food. I made an angry circuit of the massive, aircraft carrier sized hospital floor every few hours, pushing my IV stand alongside of me, weakening each day from the cumulative deficit of protein. 

 I lost more than seventeen pounds during my stay in the hospital, mostly muscle, from my inability to eat. This muscle loss contributed directly to the collapse of my left hip joint later in the spring by depriving a badly eroded arthritic joint of its supporting musculature. Escalating pain in both hips required two joint replacements in the ensuing eighteen months.   

Finally, on Sunday evening, Alex called for a pain consult, which came on Monday morning, from a brilliant young anesthesiologist named David Dickerson. The result was a nearly complete victory: a combination of an anesthetic patch, local anesthetic mouthwash for the throat, a medication intended to numb the small nerves, and a strong liquid systemic painkiller to be used as needed. I was discharged within 36 hrs. able to swallow protein drinks for sustenance. 

Unfortunately, within twenty-four hours, I was back in the University of Chicago ER for bleeding. I was readmitted for minor surgery to cauterize the wound in my throat, and also to remove fluid from one side of the neck. Finally, after recovering from the anesthesia, I was sent back to my physician’s house, which was my base camp during my Chicago stay. I flew home to Virginia two days later, on February 13. 

The saga wasn’t over. Karen, my wife, stayed with me the first four days. Despite her constant presence, neither my wife nor my guardian angel hosts in Hyde Park were given discharge instructions. Karen was barely acknowledged by any member of the care team during her four days in the hospital, despite her impending role as my caregiver. I received my discharge instructions in a haze of elation and pain meds,  and immediately tucked them away in my bag. When I arrived home in Charlottesville, exhausted from my eleven-day visit to Chicago, I showered and collapsed into my welcoming bed.

I awakened fifteen hours later with no feeling in the fingers of both hands. I also found nearly two-inch blisters on my heels from lying on my back for fifteen hours. Karen, a florist, was preoccupied by Valentine’s Day, her busiest day of the year, and my son, Trevor, who came to stay, was reluctant to disturb me. Six months later, I still had no feeling in the two outer fingers of my right hand, needless collateral damage from my treatment. I basically lost my ability to type. This avoidable complication was eventually addressed with a six-hour nerve grafting surgery at Washington University in St. Louis in October, 2015.

I’d been warned by several of my policy colleagues about selecting Medicare Advantage when I turned sixty-five. “Wait ‘till you get sick”, they sagely warned me.

In fact, my carrier, Humana, did not delay my course of therapy by five minutes, and rapidly approved my personal decision based on medical advice to seek cancer care from an NCI designated Comprehensive Cancer Center five hundred miles from home and “out of network” for my Virginia-based plan. 

Unfortunately, the MA approval process placed a huge clerical/administrative burden on my Charlottesville-based primary care physician Jeff Davis, whose long-suffering office staff was required to initiate requests for authorization for every single stage of the diagnosis and treatment, a process which consumed nearly two person days of administrative time. I did get regular check-ins from a Humana nurse for several weeks after the procedure and a big shipment of frozen meals.  

But otherwise, my Medicare Advantage plan added no value to my cancer care, and grossly underpaid the University of Chicago for my surgery. The hospital was paid $15 thousand under their Humana MA contract for my total care, not counting Alex’s surgical fee, for a complex surgery, an eight day hospital stay and an emergency readmission.

The surgical care I received at the U of C was a triumph, both thorough and definitive. It saved my life.  However, the follow up pain management and the discharge process and post-surgical recovery were disasters, both from a patient experience standpoint (fed back with verve on my HCAHPS survey!) and a cost standpoint.  

The diffusion of responsibility throughout the complex care episode, and consequent lack of ownership of my recovery, was the root cause of much of this gap. An additional learning for me:  much of the risk of any clinical intervention is borne by the family after the intervention is over. The failure to prepare my family for its role had direct consequences for me in future surgical episodes that would have been unnecessary a better scripted episode. 

A recent commenter on LinkedIn compared the “consumer” of healthcare to a person gorging on Baked Alaska in a restaurant where someone else picked up the bill. Given my own frightening experience with cancer, I found this characterization insulting and demeaning. I wasn’t “consuming” anything; I was drowning! My central challenge was finding someone I could trust to save my life. Would I have chosen someone I did not know or trust, but whose services were less costly, to rid me of my cancer? Not on your life. 

Economist Kenneth Arrow wrote sixty years ago that one thing that distinguishes medicine from other things our economy does is that illness is not only unpredictable, but also an “assault on one’s personal integrity”. Responding to that lethal uncertainty is the toughest job in our economy. I was and remain deeply grateful to my clinical team for saving my life.  

I am now nine years cancer free, and sobered by how fraught and complicated my care experience was. It is hard to describe how much fear and uncertainty I felt, even in my home institution, despite forty years of working experience in and around hospitals. When I hear marketing experts prattle on about the “consumer’s care journey”, it just makes me want to throw up.

Jeff Goldsmith is a veteran health care futurist, President of Health Futures Inc and regular THCB Contributor. This post comes from his personal substack

By KIM BELLARD

I saw a report last week – Clinician of the Future 2023 Education Edition, from Elsevier Health – that had some startling findings, and which didn’t seem to garner the kind of coverage I might have expected.  Aside from Elsevier’s press release and an article in The Hill, I didn’t see anything about it.  It’s worth a deeper look.

The key finding is that, although 89% say they are devoted to improving patients’ lives, the majority are planning careers outside patient care.  Most intend to say in healthcare, mind you; they just don’t see themselves staying in direct patient care.

We should be asking ourselves what that tells us.

The report was based on a survey of over 2,000 medical and nursing students, from 91 countries, as well as two roundtable sessions with opinion leaders and faculty in the United States and United Kingdom.  Since I’m in the U.S. and think most about U.S. healthcare, I’ll focus mostly on those respondents, except when they’re not split out or where the U.S. responses are notably different.

Overall, 16% of respondents said they are considering quitting their medical/nursing studies (12% medical, 21% nursing), but the results are much worse in the U.S, especially for medical students – 25% (nursing students are still 21%).  That figure is higher than anywhere else. Globally, a third of those who are considering leaving are planning to leave healthcare overall; it’s closer to 50% in the U.S.

Tate Erlinger, vice president of clinical analytics at Elsevier, noted: “There were several things [that] sort of floated to the top at least that caught my attention. One was sort of the cost, and that’s not limited to the U.S., but the U.S. students are more likely to be worried about the cost of their studies.”  Overall, 68% were worried about the cost of their education, but the figure is 76% among U.S. medical students (and for UK medical students).  

Having debt from their education is a factor, as almost two-thirds of nursing students and just over half of medical students are worried about their future income as clinicians, with U.S. medical students the least worried (47%).

It’s worth noting that 60% are already worried about their mental health, and the future is daunting: 62% see a shortage of doctors within ten years and 64% see a shortage of nurses. Globally, 69% of students (65% medical, 72% nursing) are worried about clinician shortages and the impact it will have on them as clinicians.

Where it gets really interesting is when asked: “I see my current studies as a stepping-stone towards a broader career in healthcare that will not involve directly treating patients.” Fifty-eight percent (58%) agreed (54% medical, 62% nursing). Every region was over 50%. In the U.S., the answer was even higher – 61% overall (63% medical, 60% nursing).

Dr. Sanjay Desai, one of the U.S. roundtable panelists, said: “I know this might evolve as they go through their education, but 6 out of 10 in school, when we hope that they’re most excited about that career, are looking at it with skepticism. That is surprising to me.” 

Me too.

The ratings on the education they are getting are good news/bad news.  Seventy-eight percent (78%) agreed that their school is “adequately preparing me to communicate and engage with a diverse patient population,” and 74% that the curriculum has been adapted to the skills that today’s clinicians need, but, honestly, wouldn’t you hope those percentages would be higher? 

Perhaps this is explained in part by only 51% reporting they have used A.I. in their training and only 43% agreeing their instructors welcome it.  The latter percentage is 49% in the U.S.  Overall, 62% are excited about the use of AI in their education, although only 55% in the U.S. (57% medical, 53% nursing).

Similarly, 62% think the potential for AI to help clinicians excites them, but only 55% in the U.S. (58% medical, 52% nursing).  Seventy percent (70%) think AI will aid in diagnosis, treatment, and patient outcomes, but, again, the U.S. lags: 64%, same for medical and nursing. Still, only 56% (globally and in the U.S.) agree that within 10 years clinical decisions will be made with the assistance of AI tool.

Dr. Desai was emphatic about use of AI: “It’s here and it’s going to stay. There are some who have said that we should slow down until the frameworks and the guardrails for ethics and for appropriate use, etc., are in place, and I think that’s wise. But I think we need to accelerate that, because as technology outpaces our organization of the space, there are risks.” Another U.S. panelist, Dr. Lois Margaret Nora, was more circumspect: “AI can turn out great, and it can turn out really terrible, and understanding the difference, I think, is an issue that is going to be very important in education.”

More broadly, 71% believe the widespread use of digital health technologies will enable the positive transformation of healthcare, although only 66% in the U.S., but 60% fear that will be a “challenging burden on clinicians’’ responsibilities.” For once, U.S. students were less pessimistic: only 52% have the same fear (51% medical, 54% nursing). 

————-

It’s disturbing but not surprising that a quarter of U.S. medical students, and a fifth of nursing students, are considering leaving school.  The lengthy time it takes and the corresponding debts are daunting.  Of more concern is that so many – over 60% for both medical and nursing students – are already planning for a career that doesn’t involve patient care. Are those schools the right place for such students?  Have careers involving direct patient care become that bad? 

It’s also clear that the world is changing more rapidly than medical/nurse schools or their students.  They’re not ready for an AI world, they’re not even fully prepared for a digital health world. These students are going to be the vanguard in deploying the new tools that are coming available, and they’re neither adequately trained nor quite enthusiastic about them.     

Jan Herzhoff, President of Elsevier Health, summarized the report’s implications: “It’s clear that healthcare across the globe is facing unprecedented pressures, and that the next generation of medical and nursing students are anxious about their future. Whether through the use of technology or engaging learning resources, we must support students with new and innovative approaches to enable them to achieve their potential. However, the issues raised in this report can’t be tackled in isolation; it is essential that the whole healthcare community comes together to ensure a sustainable pipeline of healthcare professionals.”

Let’s get on that, then.

Kim is a former emarketing exec at a major Blues plan, editor of the late & lamented Tincture.io, and now regular THCB contributor

by MIKE MAGEE

Exactly 1 year ago, mental health experts alerted the medical world to their version of an assessment scale for yet another new condition – “doomscrolling.”

As defined in the article, “Constant exposure to negative news on social media and news feeds could take the form of ‘doomscrolling’ which is commonly defined as a habit of scrolling through social media and news feeds where users obsessively seek for depressing and negative information.”

No one can deny a range of legitimate concerns. Faced with continued background noise from the pandemic, add global warming, renegade AI, and the Republican Congress. And now, the devastating attacks on Israel and growing instability in the Middle East. It is no wonder that we can’t turn off the Instagram feed.

With real challenges like these, our troubled world needs her doctors and nurses to stay focused more than ever on their primary professional missions – managing health and wellness, sickness and disease, fear and worry, and yes, now “doomscrolling.”

John J. Patrick PhD, in his book Understanding Democracy, lists the ideals of democracy to include “civility, honesty, charity, compassion, courage, loyalty, patriotism, and self restraint.” The 4.2 million registered nurses and 1 million doctors in America are agents of democracy.

Regrettably, they are already being drawn away from patients by three powerful forces.

1. Corporate Dislocation – To assure maximum reimbursement, doctors and nurses are routinely asked to prioritize time and contact with data over time and access to patients.
2. Health Technology and AI Substitution – Rather than engineering solutions to expand real-time patient contact, most innovations are further distancing patients from healthcare professionals.
3. Legislative Intrusion – Complex medical decisions, long entrusted to the patient-health professional relationship to negotiate, are being transferred to ultra-conservative legislators.

We live under a constitutional and representative democracy, as do two-thirds of our fellow citizens in over 100 nations around the world. The health of these democracies varies widely. The case for democracy emphasizes its capacity to enhance dignity and self-worth, promote well-being, advance equal opportunity, protect equal rights, advance economic productivity, promote peace and order, resolve conflicts peacefully, hold rulers accountable, and achieve legitimacy through community-based action.

One of the challenges of democracy is to find the right balance in pursuing “the common good” which has dual (and often competing) arms. One arm is communitarian well-being and the other, individual well-being.

Blending personal and public interests is complex. In health, one might argue, this tension has led to our dual system – one, largely profit driven, interventional and science discovery based, and the other largely public, preventive and focused on communitarian public health.

Both nursing and medicine have embraced professionalism and launched new graduates by voicing “oaths” or promises to themselves, their colleagues, and our society as a whole.  These lists of promises or pledges, their language and priority ordering, help reveal both the history and intent of these noble professions.

Of course, the most famous oath in Medicine is the Hippocratic Oath reaching back some 2000 years to Greece. In pledging to a grouping of ancient deities, it recognized that interventions should “do no harm” and that confidentiality was paramount.

By 1964, this oath was sufficiently out of date that many medical schools embraced an updated version written by Louis Lasagna, MD. The oath includes a communitarian connector: “I will remember that I remain a member of society, with special obligations to all my fellow human beings, those sound of mind and body as well as the infirm.”

The Penn State College of Medicine’s Oath in 2022 offered a counter-balance by giving top billing to the patient, with the oath to the patients, not to Greek gods: “By all that I hold highest, I promise my patients competence, integrity, candor, personal commitment to their best interest, compassion, and absolute discretion, and confidentiality within the law.”

The Geneva based World Medical Association, in the shadow of the Nuremberg Trials, provided a list of pledges in

their 1946 Declaration of Geneva in order of appearance including:

1. the service of humanity
2. patents first
3. patient autonomy and dignity
4. respect for human life
5. absence of bias or prejudice on any basis
6. commitment to patient privacy
7. guided by professional conscience and dignity
8. honor the noble traditions of the profession
9. respect and gratitude to teachers, colleagues and students
10. share knowledge to advance health care
11. commit to personal health and well-being
12. never violate human rights.

Nursing has also relied on professional Oaths. The first was the Nightingale Pledge, created in 1893 by the Farrand Training School for Nurses and named after Florence Nightingale. It is believed to be based on the Hippocratic Oath and was modernized in 1935. In the 1950’s, the American Nurses Association (ANA), created a formal Code of Ethics, including Nursing’s 9 Provisions (or Pledges) committing to: compassion and respect, patient-focus, advocacy, active decision making, self-health, ethical environment, scholarly pursuit, collaborative teamwork, professional integrity and social justice.

Health professionals need to be laser focused during these troubled times on patients. Doctors and nurses, day in and day out, by managing fear and worry, reinforcing community and family bonds, and championing hopefulness, guard against a true “doomsday scenario” – the destruction of our Democracy from within. The patient is our primary concern and deserves our full professional attention.

Mike Magee MD is a Medical Historian and regular contributor to THCB. He is the author of CODE BLUE: Inside America’s Medical Industrial Complex (Grove/2020).