We’re happy to hear good news, but we still need to see the data

By | Commentary, In the News | No Comments

This week, BioArctic Neuroscience, Esai, and Biogen made headlines when they announced via press release the topline and positive results of their Phase 2a study of the anti-amyloid antibody BAN2401. The press release indicated that the drug “demonstrated statistically significant slowing in clinical decline and reduction of amyloid beta accumulated in the brain” in patients with early Alzheimer’s disease.

To be sure, this is welcomed news. Too often headlines for Alzheimer’s disease clinical trials are about “flops” and “failures.” So we should take this good news and embrace it. Unfortunately, there remain many questions to which we need answers before we celebrate too much.

First, this trial was previously considered negative. The investigators from Esai and their partners are to be commended for pushing the envelope. This trial employed a complex modern protocol known as an adaptive design. The adaptive design used numerous planned analyses of data from the ongoing trial to try to “pick a winner” among five doses of the drug, funneling more patients into the best dose. Unfortunately, after enough patients had achieved 12-months of treatment, there was no winner. Despite this, the plan was always to keep the trial going until patients had received the drug for 18-months.

When the trial was analyzed in a more traditional sense, comparing the patients who got drug to the patients who got placebo for the entire 18-months, those receiving the highest dose apparently benefited most. Still, we will need to hear more about all of the groups, including how many patients were in each group and how the groups performed compared to each other. We also need to see the full safety data, though the topline report suggests that the safety profile was as good as some other antibodies in development for Alzheimer’s disease, but worse than some others.

This represents the second time that an investigational agent targeting the fibrillar form of amyloid beta that accumulates in the Alzheimer’s brain has demonstrated promising effects on both brain biomarker and clinical outcomes. These results are heartening. Nevertheless, the secondary nature of the analyses and the need for replication in Phase 3 trials warrant caution, as well as optimism.

The 90+ Study finds link between moderate Alcohol Consumption and Longevity

By | Carousel Slider | No Comments

UCI MIND faculty investigator, Dr. Claudia Kawas, presented findings from The 90+ Study at the American Association for the Advancement of Science’s annual conference this past weekend, highlighting the link between moderate alcohol consumption and longevity. In an observational study of participants age 90 and older, Dr. Kawas and her team found that consuming about two glasses of beer or wine daily was associated with 18% reduced risk of premature death. Findings also suggest regular exercise, social and cognitive engagement, and a few extra pounds in older age are associated with longevity.

To learn more about The 90+ Study, click HERE or contact 949.768.3635 or study90@uci.edu.

You can help UCI researchers better understand the keys to longevity and brain health. Enroll in the UCI Consent-to-Contact (C2C) Registry to learn about studies for which you might qualify: c2c.uci.edu

 

About the 90+ Study:

The 90+ Study was initiated in 2003 to study the oldest-old, the fastest growing age group in the United States.  The 90+ Study is one of the largest studies of the oldest-old in the world. More than 1,600 people have enrolled.  Because little is known about people who achieve this milestone, the remarkable increase in the number of oldest-old presents a public health priority to promote the quality as well as the quantity of life.

 

This study recently featured in:

TIME

Yahoo

US News & World Report

Independent UK

ABC7

KTLA 5

CBSLA/KCAL9

FOX11 LA

AOL

Other sources:

ABC10, Seattle Times, The Baltimore Sun, M Live, FOX6 Milwaukie, WDAM7, CBS13 Sacramento, WBTV, Chicago Tribune, FOX8, CBS SF BayArea, PIX 11 New York, Wave 3 News, FOX 32 Chicago, WTOL 11, VINE PAIR, WAVY TV, KPLR 11 St. Louis, WOWK TV, ABC Action News WFTS Tampa Bay, ABC11, WAOW 9, ABC30 KFSN TV Fresno, FOX10 Phoenix, CBS Pittsburgh, FOX 26 Houston, First Alert 48 WAFF, WQAD 8, ABC6 WATE, FOX29, FOX40, FOX43, NY Daily News, WREG, FOX35 Orlando, DFW CBS, KXXV Central Texas News, WAFB 9, The Fresno Bee, WTVR CBS6, WGN TV, WREG, 10News, WPTV, WWAY TV3, KIVI 6 ABC Boise/Nampa, FOX31 KDVR, WISH TV, CW 39 Houston, FOX5 San Diego, FOX Business, KFOR-TV, FOX8, FOX61, ABC13 Houston, FOX13, WNEP TV, News Channel 5 Nashville, 6ABC Action News, TMJ4, ABC7 New York, FOX6 NOW, WHNT, KTNV Channel 13 Action News, KDVR, Medical Xpress, Miami CBS Local, ABC7 Chicago, FOX61, WIAT CBS 42

Dr. Joshua Grill on Mild Cognitive Impairment

By | Carousel Slider | No Comments

UCI MIND Director, Dr. Joshua Grill, recently discussed Mild Cognitive Impairment (MCI) with Being Patient, a news site building single-subject platforms around complex health topics.

Click here to read the article and learn:

  • Is MCI reversible?
  • Is MCI a precursor to Alzheimer’s?
  • How soon will MCI progress to Alzheimer’s?
  • What are the warning signs of MCI?
  • Will I recognize my own MCI?
  • What can I do to delay MCI?

UCI MIND has a number of research studies currently enrolling people with MCI or memory concerns.  To learn about studies for which you may be eligible, enroll in the UCI C2C Registry (c2c.uci.edu), a confidential online tool to help match local volunteers with research studies at UCI.

Dr. Joshua Grill on Mild Cognitive Impairment

By | In the News | No Comments

UCI MIND Director, Dr. Joshua Grill, recently discussed Mild Cognitive Impairment (MCI) with Being Patient, a news site building single-subject platforms around complex health topics.

Click here to read the article and learn:

  • Is MCI reversible?
  • Is MCI a precursor to Alzheimer’s?
  • How soon will MCI progress to Alzheimer’s?
  • What are the warning signs of MCI?
  • Will I recognize my own MCI?
  • What can I do to delay MCI?

UCI MIND has a number of research studies currently enrolling people with MCI or memory concerns.  To learn about studies for which you may be eligible, enroll in the UCI C2C Registry (c2c.uci.edu), a confidential online tool to help match local volunteers with research studies at UCI.

Remembering the contributions of Nobel laureate Dr. Arvid Carlsson in the field of Parkinson’s disease

By | In the News | No Comments

Dr. Arvid Carlsson passed away this past Friday at the age of 95. His research into dopamine led to the development of treatments for Parkinson’s disease, a neurodegenerative disease that involves tremors and rigidity.

Dr. Carlsson showed that dopamine was a neurotransmitter and that it is critical to movement. Dopamine is depleted in Parkinson’s disease and the drug L-dopa can be used to treat patients with this neurological disease.

Dr. Carlsson’s findings earned him the 2000 Nobel Prize in Physiology or Medicine, along with noted American researchers Dr. Eric Kandel and Paul Greengard.

UCI MIND is grateful for the work of pioneering dementia researchers, like Dr. Arvid Carlsson, as we build upon their knowledge and research ways to make memories last a lifetime.

Possible link between human herpes viruses and Alzheimer’s disease

By | Commentary, In the News | No Comments

Recent scientific reports, one in the journal Neuron and another coming out in the journal Cell, present some intriguing new data indicating a link between human herpes viruses and Alzheimer’s disease (AD). Because the majority of AD cases cannot be attributed to genetics alone, there has been keen interest in finding other factors that affect the risk of developing AD. Head trauma and infections are two such factors that have received attention by researchers. With regard to infectious agents, speculation has often centered on the herpes viruses, especially herpes simplex virus 1 (HSV1). Human herpes viruses are neurotropic, which means they have an affinity for nerve cells. In fact, UCI MIND Faculty members Drs. David Cribbs, Carl Cotman and Frank LaFerla published a paper in 2000 in the journal Biochemistry where they showed HSV1, which is extremely common and causes cold sores, includes a small region that is very similar to amyloid peptide that accumulates in neuritic plaques in AD brains. Surprisingly, when they tested the virus in laboratory studies, it had many of the properties of amyloid, including killing nerve cells growing in a dish. In the more recent study, increased levels of two human herpes viruses (HHV-6A & HHV-7) were found in AD brain tissue when compared to brains from controls. The authors of those study also found that AD progression correlates with increased virus levels across multiple brain regions.

In the forthcoming Cell publication, investigators have extended the UCI report and shown that herpes virus induces Aβ peptide aggregation into plaque-like structures. Moreover, herpes virus infection rapidly seeds amyloid plaque deposition in a transgenic mouse model of AD and in 3-dimensional human neural cell cultures.

Collectively, these research reports provide support for the hypothesis that herpes viruses may be a risk factor for AD, though many in the field are recommending caution when interpreting these results. In particular, the recent studies in human tissue speak only to an association, not a causal relationship. Understanding who with herpes virus, which many of us do, develops AD and who does not may be a critical question for the field to address.

Light and electron micrographs of the assemblies formed by the Aβ and gB peptides. Aβ and gB peptides are shown on the left and right side, respectively: (a and b) light microscopy-phase contrast view, (c and d) thioflavin S staining of the peptides, and (e and f) electron micrographs of negatively stained peptide assemblies.

References:

Cribbs DH, Azizeh BY, Cotman CW, LaFerla FM. Fibril formation and neurotoxicity by a herpes simplex virus glycoprotein B fragment with homology to the Alzheimer's A beta peptide. Biochemistry. 2000 May 23;39(20):5988-94.

Readhead B, Haure-Mirande JV, Funk CC, Richards MA, Shannon P, Haroutunian V, Sano M, Liang WS, Beckmann ND, Price ND, Reiman EM, Schadt EE, Ehrlich ME, Gandy S, Dudley JT. Multiscale Analysis of Independent Alzheimer’s Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus. Neuron 99, 1–19 July 11, 2018

Eimer, William A. and Vijaya Kumar, Deepak Kumar and Shanmugam, Nanda Kumar N. and Washicosky, Kevin J. and Rodriguez, Alex S. and György, Bence and Breakefield, Xandra O. and Tanzi, Rudolph E. and Moir, Robert D., Alzheimer’s Disease-Associated β-amyloid Is Rapidly Seeded by herpesviridae to Protect Against Brain Infection (2018). Available at SSRN: https://ssrn.com/abstract=3155923 or http://dx.doi.org/10.2139/ssrn.3155923