Advertisements
Feeds:
Posts
Comments

Posts Tagged ‘AD biomarkers’


5:00 – 5:45 PM Early Diagnosis Through Predictive Biomarkers, NonInvasive Testing

Reporter: Stephen J. Williams, Ph.D.

 

Diagnosing cancer early is often the difference between survival and death. Hear from experts regarding the new and emerging technologies that form the next generation of cancer diagnostics.

Moderator: Heather Rose, Director of Licensing, Thomas Jefferson University
Speakers:
Bonnie Anderson, Chairman and CEO, Veracyte @BonnieAndDx
Kevin Hrusovsky, Founder and Chairman, Powering Precision Health @KevinHrusovsky

Bonnie Anderson and Veracyte produces genomic tests for thyroid and other cancer diagnosis.  Kevin Hrusovksy and Precision Health uses peer reviewed evidence based medicine to affect precision medicine decision.

Bonnie: aim to get a truth of diagnosis.  Getting tumor tissue is paramount as well as properly preserved tissue.  They use deep RNA sequencing  and machine learning  in their clinically approved tests.

Kevin: Serial biospace entrepreneur.  Two diseases, cancer and neurologic, have been diseases which have been hardest to get reproducible and validated biomarkers of early disease.  He concentrates on protein biomarkers.

Heather:  FDA has recently approved drugs for early disease intervention.  However the use of biomarkers can go beyond patient stratification in clinical trials.

Kevin: 15 approved drugs for MS but the markers are scans looking for brain atrophy which is too late of an endpoint.  So we need biomarkers of early disease progression.  We can use those early biomarkers of disease progression so pharma can target those early biomarkers and or use those early biomarkers of disease progression  for endpoint

Bonnie: exciting time in the early diagnostics field. She prefers transcriptomics to DNA based methods such as WES or WGS (whole exome or whole genome sequencing).  It was critical to show data on the cost savings imparted by their transcriptomic based thryoid cancer diagnostic test for payers to consider this test eligible for reimbursement.

Kevin: There has been 20 million  CAT scans for  cancer but it is estimated 90% of these scans led to misdiagnosis. Biomarker  development  has revolutionized diagnostics in this disease area.  They have developed a breakthrough panel of ten protein biomarkers in serum which he estimates may replace 5 million mammograms.

All panelists agreed on the importance of regulatory compliance and the focus of new research should be on early detection.  In addition they believe that Dr. Gotlieb’s appointment to the FDA is a positive for the biomarker development field, as Dr. Gotlieb understands the potential and importance of early detection and prevention of disease.  Kevin also felt Dr. Gotlieb understands the importance of incorporating biomarkers as endpoints in clinical trials.  Over 750 phase 1,2, and 3 clinical trials use biomarker endpoints but the pharma companies still need to prove the biomarkers clinical relevance to the FDA.They also agreed it would be helpful to involve advocacy groups in putting more pressure on the healthcare providers and policy makers on this importance of diagnostics as a preventative measure.

In addition, the discovery and use of biomarkers as disease endpoints has led to a resurgence of Alzheimer’s disease drug development by companies which have previously given up on these type of neurodegenerative diseases.

Kevin feels proteomics offers great advantages over DNA-based diagnostics, especially in cancer such as ovarian cancer, where a high degree of specificity for a diagnostic test is required to ascertain if a woman should undergo prophylactic oophorectomy.  He suggests that a new blood-based protein biomarker panel is being developed for early detection of some forms of ovarian cancer.

Please follow on Twitter using the following #hash tags and @pharma_BI

#MCConverge

#cancertreatment

#healthIT

#innovation

#precisionmedicine

#healthcaremodels

#personalizedmedicine

#healthcaredata

And at the following handles:

@pharma_BI

@medcitynews

 

Please see related articles on Live Coverage of Previous Meetings on this Open Access Journal

LIVE – Real Time – 16th Annual Cancer Research Symposium, Koch Institute, Friday, June 16, 9AM – 5PM, Kresge Auditorium, MIT

Real Time Coverage and eProceedings of Presentations on 11/16 – 11/17, 2016, The 12th Annual Personalized Medicine Conference, HARVARD MEDICAL SCHOOL, Joseph B. Martin Conference Center, 77 Avenue Louis Pasteur, Boston

Tweets Impression Analytics, Re-Tweets, Tweets and Likes by @AVIVA1950 and @pharma_BI for 2018 BioIT, Boston, 5/15 – 5/17, 2018

BIO 2018! June 4-7, 2018 at Boston Convention & Exhibition Center

https://pharmaceuticalintelligence.com/press-coverage/

Advertisements

Read Full Post »


8:20AM 11/12/2014 – 10th Annual Personalized Medicine Conference at the Harvard Medical School, Boston

REAL TIME Coverage of the Conference by Dr. Aviva Lev-Ari, PhD, RN – Director and Founder of LEADERS in PHARMACEUTICAL BUSINESS INTELLIGENCE, Boston http://pharmaceuticalintelligence.com

 

8:20 a.m. Special Guest Keynote Speaker – The Future of Personalized Medicine

The Future of Personalized Medicine

Special Guest Speaker

Margaret Hamburg, M.D.
Commissioner of Food and Drugs Administration

[Her Father was President of IOM said at the introduction to the Keynote]

How to ask the right question is what HMS taught me best 

Increasing the knowledge of Biology, response to disease, preventive strategies.

2004 — Monumental year — One year after completion of sequencing the Genome

2008/9 – Breast Cancer – pharmacotherapy approved, a protein involved in triggering the disease.Target therapy – risk of disease identified

WHAT FDA is doing on Genetics Information as PARTNERS in Medicine

25% of drugs approved are Targeted therapies

LABELING drugs on genetic information

diagnostics test — identify good respondents

Companion Diagnostics – should be used in Targeted therapies. IGF1, HER2 expression and amplification

PM more important in ONCOLOGY , HepB, Cystic Fibrosis, differential response, CVD – expansion, more to be done

In 2002 — a Program to discuss Genetic information VSDS – New Genomics Program, National Center for Toxicology Research a participants

Translational Scientist are added.

Completion Genome sequencing — push to PM 2011 – Genomics evaluation Team for Safety.

Challenge – Drug, Biologics – interaction need coordination by Agency to discuss challenges and collaboration with out side Group.

Developers of Targeted therapies: Orphan Drugs, Biomarkers – expedited review to promote innovations, fast track breakthrough therapies. Opportunities of Scientist to engage discussion with FDA

 – ALL hands on Deck Approach at FDA – making products available, i.e. SCLC (small cell lung cancer)

Since 2005 – 25 Guidance Reports, i.e., Orphan Drugs and on Companion Diagnostics to be developed in tandem with drug development.

Companion Diagnostics – 3 month review, enforcement and direction – in the framework

FDA — needs to keep up with development in the Diagnostics and in the disease ares.

Illumina – Assays using SNIPS – FDA assesses a shared curated DB on mutation, reduce the review time significantly

FDA – NGS – reference libraries, Genomics Reference and Storage of genomics data

Tools and Capabilities  – support regulatory and science, statistical methods of analysis — implemented for Breast Cancer — signaled the way of new Partnerships and New Clinical Trials formats and methods in its development.

New diagnostics – AMP Program Alzheimer’s Disease, rheumatoid arthritis (RA), inflammatory bowel syndrome (IBS)

What Science is needed for the Regulators to effectively HELP spar innovation.

Pharmacogenomics, Pharmacogenetics — MAPPING the Human Genome and all other areas of “OMICS” – moving from Lab to bedside — requires expertise in Disease prevention, Difference in patients life, Standard medical practice

  • Biology and Pathways
  • Biomarkers
  • New diagnostics
  • Increased communication Universities, new paradigms models and continual effort of SHARING and coordination of shared resources

 

– See more at: http://personalizedmedicine.partners.org/Education/Personalized-Medicine-Conference/Program.aspx#sthash.qGbGZXXf.dpuf

 

@HarvardPMConf

#PMConf

@SachsAssociates

Read Full Post »


Author: Tilda Barliya PhD

Alzheimer disease (AD) is among the most common brain disorders affecting the elderly population the world over, and is projected to become a major health problem with grave socio-economic implications in the coming decade (1a, 1b). Alzheimer’s disease arises in large part from the body’s inability to clear these naturally occurring proteins. As amyloid beta levels increase, they tend to aggregate and contribute to the brain “plaques” found in Alzheimer’s disease. There are still no effective treatments to prevent, halt, or reverse Alzheimer’s disease, but research advances over the past three decades could change this gloomy picture. Genetic studies demonstrate that the disease has multiple causes (2). Interdisciplinary approaches have been used to reveal the molecular mechanism of the disease including; biochemistry,  molecular and cell biology and transgenic mice models.  Progress in chemistry, radiology, and systems biology is beginning to provide useful biomarkers, and the emergence of personalized medicine is poised to transform pharmaceutical development and clinical trials. However, investigative and drug development efforts should be diversified to fully address the multifactoriality of the disease (2). A nice research review shows  for example, the effects of cancer drugs on AD treatment (3).

Nanotechnology Solutions for Alzheimer

Dr. Amir Nazem and Dr. G. Ali Mansoori described in their paper “Nanotechnology Solutions for Alzheimer’s Disease: Advances in Research Tools, Diagnostic Methods and Therapeutic Agents”
that he development of nanotechnology approaches for early-stage diagnosis of AD is quite promising but acknowledge that scientists are still at the very beginning of the ambitious project of designing effective drugs and methods for the regeneration of the central nervous system (4). Figure 1- Nanotechnology solutions of AD.

Applications of nanotechnology in AD therapy including:

  • Nanodiagnostics including imaging
  • Targeted drug delivery and controlled release
  • Regenerative medicine

These inclued: neuroprotections against oxidative stress anti-amyloid therapeutics, neuroregeneration and drug delivery beyond the blood brain barrier (BBB) are discussed and analyzed.

All of these applications could improve the treatment approach of AD and other neurodegenerative diseases.

Nanotechnology and Diagnostics:

The diagnosis of AD during life remains difficult and a definite diagnosis of AD relies on histopathological confirmation at post-mortem or by cerebral biopsy.  An early clinical diagnosis can be made if patients  are tested by trained neuropsychologists. The great problem is not that mild cognitive impairment  (MCI) cannot be diagnosed, but that the patients do not see doctor until severely affected (5).

During the last decade, research efforts have focused on developing  cerebrospinal fluid (CSF) biomarkers for AD. The diagnostic performance of the CSF  biomarkers: Tau protein, the 42-amino acid form of beta amyloid (Aβ42) and Amyloid  Precursor Protein are of great importance. One possible biomarker for Alzheimer’s is  amyloid beta-derived diffusible ligands (ADDL). The correlation of CSF ADDL levels  with disease state offers promise for improved AD diagnosis and early treatment. Singh et al have developed ADDL-specific monoclonal antibodies with an ultrasensitive,  nanoparticle-based protein detection strategy termed biobarcode amplification (BCA) (5).

The BCA strategy used by Klein, Mirkin and coworkers makes clever use of nanoparticles as DNA carriers to enable millionfold improvements over ELISA sensitivity. CSF is first exposed to monoclonal anti-ADDL antibodies bound to magnetic microparticles. After ADDL binding, the microparticles are separated with a magnetic field and washed before addition of secondary antibodies bound to DNA:Au nanoparticle conjugates. These conjugates conatin covalently bound DNA as well as complementary “barcode” DNA that is attached via hybridization. Unreacted antibody:DNA:Au nanoparticle conjugates are removed during second magnetic separation, after which elevated temperature and low-salt conditions release the barcode DNA for analysis.

“Such a sensor must be able to transmit any biomarker detection event to an external device that records the transmitted signals and reports an estimated amount for the concentration of AD biomarkers in the CSF. Of course, in order to send such biosensor to a place exposing with CSF, it is necessary to design noninvasive approaches.” (4)

Nanotechnology and treatment:

Presently there exist no therapeutic methods available for curing AD [84]. The cure for AD would require therapeutics that will cease the disease progress and will reverse its resultant damages. Today, common medications for AD are symptomatic and aim at the disrupted neurotransmission between the degenerated neurons. Examples of such medications are acetylcholine esterase inhibitors, including tacrine, donepezil, rivastigmine and galantamine (4).

Design of each mechanistic therapeutic is for targeting a different stage of the AD pathogenetic process and therefore help to cease the progress of the disease. Currently there are 5 mechanistic therapeutic molecular approaches:

  • Inhibition of Aβ production;
  • Inhibition of Aβ oligomerization,
  • Anti-inflammation,
  • Cholesterol homeostasis modulating;
  • Metal chelation

The nanotechnology approaches are:

  • Drug discovery and monitoring
  • Controlled release
  • Targeted drug delivery

For example: Neuroprotection

Oxidative stress and amyloid induced toxicity are two basic toxicity processes in AD pathogenesis.

Oxidative stress protection:

Fullerene is a nanotechnology building block and can be used to design neuroprotective compounds. It’s chemical structure is known for it’s anti-oxidative and free-scavenger potentials. Applications of functionalized fullerene derivatives including carboxyfullerene and hydroxyfullerene (fullerenols), are promising in discovery of new drugs for AD; however further research on their pharmacodynamic and pharmacokinetic properties is necessary.

Anti-amyloid protections:

Nanotechnology has recently offered some antiamyloid neuroprotective approaches against the cellular and synaptic toxicity of oligomeric and fibrillar (polymeric) Aβ species. The current ongoing nanotechnology research categories on anti-amyloid neuroprotective approaches are the following three:

  1. Prevention from assembly of Aβ monomers
  2. Breaking and resolubilization of the oligomeric or fibrillar (polymeric) Aβ species
  3. Prevention from toxic effects of Aβ

Summary:

AD is a very common disease worldwide,  Solving the major problems of early diagnosis and effective cure for AD requires interdisciplinary research efforts. Research on the basic pathogenetic mechanisms of the disease has provided new insight for designing diagnostic and therapeutic methods. Nanotechnology has great potential in aiding and providing tools for diagnosing and treating AD. However, these research combining nanotechnology is still at very early stages and continuous understanding of the disease, neuronal protection and regeneration are needed in order to alleviate the symptoms of the disease.

Ref.
1a. D. G. Georganopoulou et al., “Nanoparticle-based Detection in Cerebral Spinal Fluid of a Soluble Pathogenic Biomarker for Alzheimer’s Disease”, Proc. Natl Acad Sci., 102 (2005) 2273-2276

1b D.A. Davis, W. Klein and L. Chang, “Nanotechnology-based Approaches to Alzheimer’s Clinical Diagnostics”, Nanoscape, 3 (2006) 13-17.
Read more: http://www.nanowerk.com/spotlight/spotid=23726.php#ixzz2NWlx6jYa

2. Huang Y and Mucke L. Alzheimer mechanisms and therapeutic strategies. Cell. 2012 Mar 16;148(6):1204-22.

http://www.cell.com/abstract/S0092-8674(12)00278-4

http://www.ncbi.nlm.nih.gov/pubmed/22424230

3. Cancer Drug Shows Promise in Alzheimer’s Treatment: Helps clear plaque and improve brain function in mice. Alzheimer’s Disease Research is a program of the American Health Assistance Foundation. http://www.nanowerk.com/spotlight/spotid=5262.php

4. Amir Nazem1, G. Ali Mansoori. Nanotechnology solutions for Alzheimer’s disease: advances in research tools, diagnostic methods and therapeutic agents. J Alzheimers Dis. 2008 Mar;13(2):199-223.  http://www.ncbi.nlm.nih.gov/pubmed/18376062?dopt=Abstract.

Full text: http://www.uic.edu/labs/trl/1.OnlineMaterials/08-Nanotechnology_Solutions_for_Alzheimer’s_Disease.pdf

5. Shinjini Singh, Mritunjai Singh, I. S. Gambhir*. Nanotechnology for Alzheimer’s Disease Detection. Digest Journal of Nanomaterials and Biostructures Vol. 3, No.2, June 2008, p. 75 – 79 .

http://www.chalcogen.infim.ro/Singh-Gambhir.pdf

Read Full Post »