Connect with us

Science

Why We Need an Alzheimer’s Moonshot in 2022

By Sungho Han, PhD, and Allan I. Levey, MD, PhD When science changes, it often takes a long time for nonscientists to catch up. The prevailing belief for…

Published

on

By Sungho Han, PhD, and Allan I. Levey, MD, PhD

When science changes, it often takes a long time for nonscientists to catch up.

Sungho Han, PhD
Founder and CEO, Genuv

The prevailing belief for many decades was that humans are born with a fixed number of brain cells, or neurons, and those hardy cells needed to last a lifetime. But many would unfortunately be lost prematurely due to the use of alcohol and participation in violent sports.

Nothing could be further from the truth. Nearly 50 years ago, researchers discovered new neurons in the brains of rats. We now have a clearer understanding of how neurogenesis—the formation of new neurons and other types of brain cells—occurs in specific parts of the brain throughout life. The no-new-neuron orthodoxy had been overthrown.

Nevertheless, the general public—and even some scientists—still believe the “no new neurons” doctrine. Just a few years ago, when applying for a government grant to support a drug discovery platform, one of us (Han) faced scathing personal criticism from a cell biologist. During a meeting in support of Han’s grant application, the visibly irritated cell biologist insisted that it was “absolute nonsense” to say that adults had neural stem cells capable of differentiating to mature neurons.

Allan I. Levey, MD
Allan I. Levey, MD, PhD
Emory University

We now know that olfactory neurons, responsible for the sense of smell, and hippocampal neurons, responsible for memory and other cognitive processes, are renewed throughout the human lifespan. But as to the ultimate causes of Alzheimer’s disease (AD), there is much left to uncover. Although we know that AD has a strong genetic component, we still don’t fully understand AD’s underlying genetic factors and how they interact with environmental and lifestyle risk factors.

An urgent need to consider new ideas

Some scientists and drug companies, driven by the pathological features of AD, have been heavily attached to the persistent but as-yet-unproven toxic amyloid hypothesis. This view of AD focuses drug development on the prevention or removal of amyloid beta plaques, accumulations of extracellular protein that are AD’s pathological hallmark. While there is still debate on whether the plaques cause or result from sporadic AD,1 many companies have pursued treatments that target the plaques. One of these companies is Biogen, the developer of Aduhelm, an amyloid beta–directed antibody that was approved by the U.S. Food and Drug Administration (FDA) last summer.

Neural stem cells
Neural stem cells derived from an animal model of Alzheimer’s Disease by scientists at Genuv Inc.

The deliberations over Aduhelm were fraught, and the drug’s approval quickly sparked controversy. We see the issues with Aduhelm as representative of the difficulties of treating a disease with multiple complex factors and an as-yet-unknown cause. Indeed, some researchers now fear the FDA’s approval could stymie development of novel, more effective AD treatments.2 They believe more companies will focus on drug mechanisms similar to the one for Aduhelm. Drug candidates that support different theories of the causes of AD could languish, while “a flood of drugs targeting amyloid plaques could be unleashed.”3

But the need to defeat AD is more urgent than ever. As the population in the developed world ages, more people than ever are expected to develop late-onset AD, straining caregivers, the healthcare system, and government resources. The number of people with AD is expected to triple by 2050.4 Already, there are more than 6 million people with AD in the United States.

Arizona, which has a high percentage of retirees, is expected to face an unusually severe crisis. In 2020, the Alzheimer’s Association projected that in Arizona, the number of adults aged 65 and older with AD would increase by a whopping 33% by 2025.5

Prerequisites for taking a moonshot approach

This devastating but entirely predictable health crisis requires a new approach toward solving the mysteries of degenerative neurological diseases and finding effective treatments. The “moonshot” approach—inspired by President Kennedy’s 1961 speech calling for the United States to land men on the moon by the end of the decade—has become a sort of cultural shorthand for solving a societal challenge with a determination to succeed and an urgent, all-hands-on-deck attitude. And that is exactly what’s called for in defeating AD. Here’s how we can do it:

  • Overhaul the regulatory framework for AD. If new drug development for AD were treated more like orphan drug development is treated by the FDA, communications between drug companies and FDA regulators would be facilitated at the preclinical R&D stage. This would speed discovery and clinical development and help companies make more efficient use of R&D expenditures.
  • Cultivate a more open science ecosystem. Although research collaborations and open sharing of data are increasing—the National Institutes of Health’s Accelerating Medicine Partnership for Alzheimer’s Disease is a good example—much progress is still thwarted by researchers hoarding data and samples in both academia and industry. The Collaborative Trajectory Analysis Project, a nonprofit bringing together all stakeholders in the fight against Duchenne muscular dystrophy, provides a useful example of how drug companies, academics, and patient advocates can share data and work together to speed development of new treatments.
  • Organize a drug manufacturing consortium. For amyotrophic lateral sclerosis in particular, companies and researchers need help manufacturing enough drug substance and establishing manufacturing processes for small clinical trials, especially for early-phase trials. This is an enormous expense. A not-for-profit consortium for GMP manufacturing of experimental treatments across borders would speed trials.
  • Arrange long-term longitudinal trials. Long-term longitudinal trials can enhance our understanding of how AD slowly evolves in the 20-year period before patients show symptoms.

Projects that could be expedited with a moonshot approach

After a combined 60 years in neuroscience research and drug development, we do not expect miracles. It is unlikely we will see a new, paradigm-shifting treatment approved within the next five years. But researchers will advance new theories of the cause of AD, and clinical trials will bring experimental treatments closer to patients in need. In particular, we expect to see progress on a number of fronts:

  • Neuroprotection and neuroregeneration. Better neuroprotective therapeutics will help maintain homeostasis in the brain to preserve neurons and functional neural circuits, and better regenerative therapeutics will enable more brain cells to develop in the parts of the brain where they are needed.
  • Waste clearance. Gene therapies will allow more efficient or better targeted disposal of amyloid plaques, tau tangles, and other waste products or malformations. Such treatments may be useful even if AD is not the result of the waste products, but is, rather, the cause.
  • New formulations and delivery vehicles. Treatments that cross the blood-brain barrier more easily will be more useful for treating diseases of the central nervous system.
  • Immunomodulation. Immuno-oncology drugs are being repurposed to modify the course of neurodegenerative diseases, and a new class of immuno-neurology drugs is being created.
  • Gut-brain axis. We are just beginning to understand the gut-brain axis, but it appears to present targets for AD drugs.

From small steps to giant leaps

In addition to pursuing the discovery projects mentioned earlier in this article, drug developers will explore possibilities that haven’t even been imagined yet. It’s impossible to say which advances will finally enable us to defeat AD. But certainly, it would be better to know sooner than later. Let’s launch the Alzheimer’s moonshot right away.

 

Sungho Han, PhD, is founder and CEO of Genuv, a clinical-stage biopharma company in Seoul, South Korea, that develops treatments for cancer and degenerative neurological diseases. Allan I. Levey, MD, PhD, is a neurologist and neuroscientist at the Emory University School  of Medicine who advises Genuv.

 

References
1. Thomas KR, Bangen KJ, Weigand AJ, et al. Objective subtle cognitive difficulties predict future amyloid accumulation and neurodegeneration. Neurology 2020; 94(4): e397–e406.
2. McGinley L. The controversial approval of an Alzheimer’s drug reignites the battle over the underlying cause of the disease. Washington Post. Published: July 16, 2021. Accessed: March 29, 2022.
3. Sachs R. The FDA’s Approval Of Aduhelm: Potential Implications Across A Wide Range Of Health Policy Issues And Stakeholders. Health Affairs. Published: June 10, 2021. Accessed: March 29, 2022.
4. Kapadia R. The Other Pandemic: What to Do About the Coming Alzheimer’s Crisis. Barron’s. Published: February 5, 2021. Updated: February 7, 2021. Accessed: March 29, 2022.
5. Suneson G, Byrnes H. Alzheimer’s disease to affect 7.1 million Americans by 2025. Here’s the expected increase by state. USA Today. Published: August 10, 2020. Accessed: March 29, 2022.

The post Why We Need an Alzheimer’s Moonshot in 2022 appeared first on GEN - Genetic Engineering and Biotechnology News.

Read More

Continue Reading

Science

Is Plan B The New Baby Formula?

After the Roe v. Wade reversal, some grocery stores are limiting the number of products one can purchase.

Published

on

After the Roe v. Wade reversal, some grocery stores are limiting the number of products one can purchase.

The ripple effects of the Supreme Court's overturning Roe v. Wade are just starting to trickle through into a wide range of industries and fields.

One such ripple effect is the widespread purchasing of emergency contraception -- drugstore chain CVS  (CVS) - Get CVS Health Corporation Report recently announced that it was placing caps on the number of Plan B and Aftera products customers can buy at a time to "ensure equitable access and consistent supply on store shelves."

The two are some of the most common brand names of the "morning after pill," which is commonly taken after an unprotected sexual encounter or failure of one's regular birth control.

The active drug in them is Levonorgestrel, which prevents ovulation or eggs from attaching to the uterus. Plan B and Aftera cost a respective $49.99 and $39.99 and are available over the counter.

"We have ample supply of Plan B and Aftera across all of our CVS Pharmacy stores and CVS.com," CVS Health Spokesperson Ethan Slavin said in a statement. "To ensure equitable access and consistent supply on store shelves, we’ve implemented a temporary purchase limit of three on these products."

This Is Very Different From Baby Formula

Most recently, CVS and other drug store chains Target  (TGT) - Get Target Corporation Report and Walgreens  (WBA) - Get Walgreens Boots Alliance Inc. Report placed similar limits on how many boxes of baby formula customers could buy at a time.

Back in April, out-of-stock rates for formula reached 31% nationwide and over 50% in states like Texas, North Dakota, South Dakota, and Tennessee amid pandemic-related supply chain issues and one of the country's largest producers closing a plant due to an FDA recall.

But while shortages of baby formula can be attributed to external factors that limited the numbers of available products, morning after pill limits appear directly linked to the panic coming from the Supreme Court's decision. 

According to CVS, the limits were put in place to prevent panic-buying and profiteering rather than due to a product shortage.

Shutterstock

The repeal of Roe v. Wade, which was put in place in 1973, gives states individual power to ban or severely restrict abortion.

Analysts expect this to happen in roughly half of all states (the divide, as with many other things, will likely take place between "red" and "blue" states) while 13 states with "trigger bans" are already enacting laws to prohibit abortion in the next 30 days.

In one abortion clinic in Texas, providers fearful of violating the law were calling to cancel appointments within hours of the Supreme Court ruling. 

As a result, many women in states most at risk of strict bans may be feeling panicked about the future.

As seen during the pandemic and the numerous shortages that came up in the aftermath, panic-buying can impact the supply chain and create very real shortages.

What Will Demand Be Like In A Post-Wade Future?

By Monday, reports started to come in of Walgreens  (WBA) - Get Walgreens Boots Alliance Inc. Report and Rite Aid  (RAD) - Get Rite Aid Corporation Report enacting similar purchase limits. 

Some Plan B boxes on Amazon  (AMZN) - Get Amazon.com Inc. Report are also already being listed for above retail price.

The limit imposed by CVS was, as of June 28, three per customer. While the immediate rush of purchases is likely to die down after immediate news of the reversal, many health care advocates are already preparing for major upheaval in the public health care system, from states that do not ban abortions seeing large rushes of out-of-state women to larger demand for other types of contraception.

Read More

Continue Reading

Science

Long COVID: female sex, older age and existing health problems increase risk – new research

A new study has analysed UK data from long-term health surveys and electronic health records to understand how common long COVID is, and who might be at…

Published

on

shurkin_son/Shutterstock

About 2 million people in the UK currently have long COVID, according to the latest data from the Office for National Statistics.

In the UK, long COVID is defined as “signs and symptoms that continue or develop after acute COVID-19”. This definition is further split into people who have symptoms between four to 12 weeks after infection (ongoing symptomatic COVID-19) and for 12 weeks or more (post-COVID syndrome).

Symptoms can include fatigue, breathlessness, difficulty concentrating and many more – but the precise nature of the symptoms is not well understood. There are also gaps in our knowledge when it comes to the frequency of long COVID, and whether there are particular factors that put people at higher risk of developing the condition.

All of this is partly because the symptoms used to define long COVID often vary between studies, and these studies tend to be based on relatively few people. So the results may not apply to the wider population.

In a new study published in the journal Nature Communications, my colleagues and I looked at data from ten UK-based long-term studies, alongside 1.1 million anonymised electronic health records from English general practices. Based on this data, we investigated whether the burden of long COVID (how common it is) differs by demographic and health characteristics, such as age, sex and existing medical conditions.

The studies were established before the pandemic, and have tracked participants over many years. From these surveys, we used data from 6,907 people who self-reported they’d had COVID-19. Comparing this with the data from the electronic health records of people diagnosed with COVID allowed us to examine the frequency of long COVID in those who have seen their GP about it and those who haven’t.


Read more: Long COVID: a public health expert’s campaign to understand the disease


We found that of the people who self-reported having COVID in the studies, the proportion who reported symptoms for longer than 12 weeks ranged between 7.8% and 17%, while 1.2% to 4.8% reported “debilitating” symptoms.

In the electronic health records, we found that only 0.4% of people with a COVID diagnosis were subsequently recorded as having long COVID. This low proportion of diagnoses by GPs may be partly because formal logging of long COVID was only introduced for doctors in November 2020.

COVID-19 National Core Study, Author provided

The proportion of people who reported symptoms for more than 12 weeks varied by age. There was also a lot of variation depending on which definition each study used to capture long COVID. But overall, we found evidence to suggest an increased risk of long COVID was associated with increasing age up to age 70.

The studies include participants across a range of ages, from an average age of 20 to 63. Using a strict definition of symptoms affecting day-to-day function, we found that the proportion of people with symptoms for 12 or more weeks generally rose with increasing age, ranging from 1.2% for 20-year-olds to 4.8% for those aged 63.

We also found that a range of other factors is associated with a heightened risk of developing long COVID. For instance, being female, poorer pre-pandemic mental health and overall health, obesity and having asthma were also identified as risk factors in both the long-term studies and electronic health records.

These findings are broadly consistent with other emerging evidence on long COVID. For example, a recent international review study concluded that women are 22% more likely than men to experience long COVID.


Read more: COVID: long-lasting symptoms rarer in children than in adults – new research


It will be important to understand why these links exist, which is beyond the scope of our research. But identifying who may be at higher risk of long COVID is important, and as we continue to learn more, this could inform public health prevention and treatment strategies.

Ellen Thompson does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

Read More

Continue Reading

Spread & Containment

U.S. FDA will decide on redesigned COVID vaccines by early July

U.S. regulators plan to decide by early July on whether to change the design of COVID-19 vaccines this fall in order to combat more recent variants of…

Published

on

U.S. FDA will decide on redesigned COVID vaccines by early July

By Michael Erman

“The better the match of the vaccines to the circulating strain we believe may correspond to improve vaccine effectiveness, and potentially to a better durability of protection,” Dr. Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, said at a meeting of outside advisers to the regulator.

Vials with Pfizer-BioNTech and Moderna coronavirus disease (COVID-19) vaccine labels are seen in this illustration picture taken March 19, 2021. REUTERS/Dado Ruvic/Illustration

The committee is scheduled to vote on a recommendation on whether to make the change later on Tuesday.

The updated shots are likely to be redesigned to fight the Omicron variant of the coronavirus, experts say. read more The exact composition of the retooled shots and whether they also will include some of the original vaccine alongside new components will be considered at the meeting.

Pfizer Inc (PFE.N), Moderna Inc (MRNA.O) and Novavax Inc. (NVAX.O) are scheduled to present data at the meeting. All three companies have been testing versions of their vaccines updated to combat the BA.1 Omicron variant that was circulating and led to a massive surge in infections last winter.

Both Moderna and Pfizer with partner BioNTech (22UAy.DE) have said that their respective redesigned vaccines generate a better immune response against BA.1 than their current shots that were designed for the original virus that emerged from China.

They have said that their new vaccines also appear to work against the more recently circulating BA.4 and BA.5 Omicron subvariants, even though that protection is not as strong as against BA.1.

Experts also want to know if the new shots will boost protection against severe disease and death for younger, healthier people or merely offer a few months’ additional safeguard against mild infection.

Scientists who have questioned the value of booster shots for young and healthy people have said a broad campaign is not needed with an updated shot either.

Other experts have championed any additional protection new vaccines may offer.

Reporting by Michael Erman Editing by Bill Berkrot and Bernadette Baum

Our Standards: The Thomson Reuters Trust Principles.

Source: Reuters

 

Read More

Continue Reading

Trending