Using Stem Cells and HCA to Discover Drugs.

San Francisco — Fairmont Hotel January 10, 2013.  While taking a break from my reportage of the JP Morgan Healthcare Conference and the Biotech Showcase 2013, it came to my attention that I should checkout the CHI meeting at the Fairmont Hotel.  Cambridge Healthtech Institute’s High-Content Analysis meeting was winding down its meeting so I was able to briefly see the exhibits and see a few minutes of a session about HCA in stem cells.

Mark Mercola , PhD. gave a talk called HCS to Discover Drugs for Heart Failure.  Dr. Mercola is Director, Muscle Development and Regeneration Program Sanford Burnham Medical Research Institute

Mercola talked was about studying cardiomyocytes with instrument based iPS disease models.  He used the KIC (kinetic imagery cytometry) instrument from VALA Sciences, Inc. to run his disease-in-a-dish screening assay that put iPS cells in dishes to then analyze and identify miRNAs that target heart failure.  His goal is to try to restore the calcium channel in heart failure.

He said that miRNA are efficient to target multiple proteins. He noted that this process to discover a drug is better than with direct targeting.  Dr. Mercola said that he developed a target sensor screen. He looked at 900 miRNA and picked the eGFP miRNA.  He picked the conserved human miRNA and used the best ten.  He checked each sample with the KIC instrument. Mercola created an anti-mir to target miRNA in cardiomyocytes. The in vitro experiments helped identify the in-vitro move to in-vivo.  He simulated heart failure by squeezing the rat aorta to create heart failure over next 3 months.  He said that the increased pressure in the heart leads to fibrosis.

After the talk. I spoke with several exhibitors including Eugene Cho from VALA Sciences, Inc.  The  CHI meeting had about 300 attendees.

Circulating Tumor Cells Emerging as a Hot Topic In Cancer Research

While visiting CHI’s Molecular Medicine Tri-Conference back on February 20th at the Moscone Convention Center, in  San Francisco, I had a chance to walk around the exhibit hall and talk with some of the people working at their trade show booths.

I spoke with Sally Hall, who was working at the Transgenomic, Inc. booth, and asked her, “What are some of the hot topics at the show?.” She said that it seems that this year, a hot topic at the CHI MMTC is about circulating tumor cells (CTCs).  Sally said that “this year there are about twenty companies working in this field.”

I mentioned that I noticed that the number of conference talks about CTCs at the CHI MMTC had grown over the last three years.  She agreed that she had seen increased research activity in the CTC field.

As I understand it, when cancer tumors reach a certain size or age, some of the cells break off and migrate through pores in the walls of  blood vessels and circulate in the blood stream as CTCs. The CTCs may remain dormant for months or years in the circulatory system before migrating through pores in the blood vessels to spread to other organs or tissues.

Scientists are using CTCs as a new type of biomarker.  Several research tools and technology companies have developed technology platforms to identify, isolate or characterize CTCs.

Some companies are working to develop a platform that utilizes CTCs as basis for a future personalized diagnostic.  Researchers might someday develop blood  tests that can accurately identify specific kinds of cancer tumors long before they spread to other organs.  Blood test based companion diagnostics might be developed using CTCs in concert with targeted medicines to kill tumor cells before a cancer tumor has a chance to spread.

On the other side of the exhibit hall, I spent a few moments to see a talk from the founder of Rarecells, Inc.who discussed their progress in developing a CTC-based diagnostic method that they called ISET.  I was impressed by their concept. The table below lists a few of the commercial companies working in CTCs.  Whereas the CTC field is an emerging niche market today, it may be too soon to tell what the size and shape that this market might take.

Selected companies working in CTCs

Application	Company	Comment
Clinical Use of CTCs	Fluxion Biosciences, Inc.	IsoFlux system for  analyzing CTCs
Clinical Use of CTCs	On-Q-ity, Inc.	Microfluidic system for selecting CTCs
Clinical Use of CTCs	BioCept, Inc.	OncoCEE™ Platform for capture and detecting CTCs for molecular analysis
Clinical Use of CTCs	Rarecells, Inc.	ISET, a diagnostic method for isolation and immuno-molecular characterization of CTCs
CTCs in Clinical Trials	Johnson and Johnson, Oncology Biomarkers	Liquid biopsy – the use of CTCs in clinical trials as prognostic and predictive markers.
Novel Technologies	ScreenCell, Inc.	A mini device to isolate rare circulating tumor cells (CTCs).
Novel Technologies	Advanced Cell Diagnostics, Inc.	The CTCscope platform for detection and character-ization of CTCs

Vitamin D Controversy Leaves Many Confused

On May 24, 2012, I watched an online presentation given by Neil Binkley, M.D.  (University of Wisconsin School of Medicine and Public Health) at the 3rd Annual Clinical Diagnostics BioConference Live virtual event sponsored by LabRoots.com.  His topic was “Vitamin D, Common Sense and the Goldilocks Principle.”  Binkley presented some very interesting statistics about vitamin D and how it may or may not effect our health.

He is not surprised that clinicians and the lay public are confused.  It is also not a surprise to anyone that people around the world are not getting enough vitamin D.  Some of the reasons for this include not enough in our diet, low sun exposure, and greater skin pigmentation.  I know that I worry about being in the sun too much because of skin cancer worries so I take calcium with vitamin D supplements.  However, the latest news about the dangers of too much calcium weigh on my mind.

Binkley talked about the one size fits all idea.  We need to recognize that we are not all the same.  I agree that you cannot give the same daily recommendations for everyone.  Expert guidelines differ widely.  For example, the Ministry of Health for Australia and New Zealand recommend 200-600 IU daily.  The Endocrine Society recommends 1500-2000 IU daily.  This is a very broad gap.  “We need to recognize that public health guidelines differ from patient care,” said Binkley.

He also said that despite issues and uncertainties, 25(OH)D measurement is currently accepted as the best measure of an individual’s Vitamin D status and he agrees with Mark Bolland and others that we don’t need to meta-analyses inadequate data.  He urges the Vitamin D field to stop the “boxing matches” over this issue.  He believes clinicians should take a common sense approach with their patients.  According to the American Association of Clinical Endocrinologists, 1000-2000 IU of Vitamin D daily is required to maintain a 25(OH)D level at 30 ng/ml or above.

Binkley concluded by saying that “vitamin D inadequacy is common,  but fixing this is cheap and virtually side effect free.”  There is not a downside to aiming for 25(OH)D in the 30-50 ng/ml range.  This may require around 800-1000 IU/day (or more).  He also said that vitamin D is not the “fountain of youth”, but has a number of health benefits beyond bone.  It may also reduce all-cancer risk in postmenopausal women.  It is always best to talk to your doctor and have them decide what is best for you while the controversy rages on.  Like “Goldilocks” when looking for what is just the right amount, Binkley believes that the 30-40 ng/ml range is just right.