Friday, June 29, 2018

News from ADA 2018

The American Diabetes Association's Scientific Sessions for 2018 (called ADA2018 with hastag #2018ADA) just ended.  I was not there, but did monitor twitter and other social media to get a feel for what was going on.  As in previous years, it was about 90% type-2 and about 90% treatments (not cures), and of the remaining type-1/cure research, only a little was human trials of the type covered in this blog.

So anyway, here is a huge list of links (mostly links to tweets) which I found interesting for one reason or other.  I've tried to categorize them, and in a few cases, after the link, I've added a sentence or two about why I found them interesting.

Summary web sites:
https://beyondtype1.org/breaking-news-from-ada2018/
https://www.healio.com/endocrinology/meeting-news/ada-conference
https://www.diabetesdaily.com/blog/clinical-trials-in-type-1-diabetes-ada-2018-580153/
https://www.medscape.com/viewcollection/34397
http://www.mdmag.com/conference-coverage/ada-2018

Cure Related
ATG/GCSF:
    https://twitter.com/BeyondType1/status/1011252403079745536
    https://twitter.com/Judithendo/status/1011240300742893568
Meta-Dopa, which I need to blog about:
    https://twitter.com/Judithendo/status/1011291591875743744
Encapsulation for beta cells (animals, I think):
    https://twitter.com/Cristob_Morales/status/1011230794831089667

Smart Insulin:
https://twitter.com/mbotana/status/1010599897987473410
https://pubs.acs.org/doi/abs/10.1021/acsnano.7b08152

ViaCyte:
https://twitter.com/ViaCyte/status/1010508277766082560
https://twitter.com/ViaCyte/status/1010493177273442304
https://viacyte.com/archives/press-releases/two-year-data-from-viacytes-step-one-clinical-trial-presented-at-ada-2018

Artificial Pancreas:
There were lots more, but these really called out to me.
https://twitter.com/danamlewis/status/1010527143938416641
https://openaps.org/2018/06/23/detecting-insulin-sensitivity-changes-for-individuals-with-type-1-diabetes-with-autosensitivity-from-openaps-poster-presented-at-american-diabetes-association-scientific-sessions-2018ada/
https://www.healio.com/endocrinology/diabetes/news/online/%7B904dc31d-db81-47e7-9a82-c183e2aca8c4%7D/6-month-implantable-cgm-safe-accurate-in-teens-adults

General Interest:
https://twitter.com/em_saidwhat/status/1010513691056451584
Pregnancy: https://twitter.com/RenzaS/status/1010494620512473088
Average A1c by age: https://twitter.com/RenzaS/status/1010476210088886272
Vit D: https://twitter.com/cristinatejerap/status/1010589989678305280
T2D delays T1D? https://twitter.com/cristinatejerap/status/1010604154186817537
Mice vs. Humans: https://twitter.com/Cell_Onion/status/1010543301580279808
Gut not important? https://twitter.com/DrKirstieBell/status/1010618697440989184
Patch Pump: https://www.healio.com/endocrinology/diabetes/news/online/%7B8540d455-ebc8-4e78-a1dc-f4440bc9cf18%7D/investigational-patch-pump-artificial-pancreas-safe-effective-under-free-living-conditions
Half Units Matter: https://twitter.com/Diabetes_Videos/status/1011391416889696256
Adjunct Therapy: https://www.boehringer-ingelheim.com/press-release/type-1-diabetes?
Bariatric Surgery T1D: https://twitter.com/Ali_Aminian_MD/status/1011647953667272704
SGLT:
    https://twitter.com/MarkHarmel/status/1011646768776392705
    https://twitter.com/AmDiabetesAssn/status/1010860753589587968
    https://www.healio.com/news/online/%7B943b8bde-157a-4d87-ae3c-5f1f1d2fe2d5%7D/dual-sglt-inhibitor-boosts-insulin-efficacy-in-type-1-diabetes
New Patch Pump: https://twitter.com/SanofiDCV/status/1011617549174353920

Type-2:
Lots of comorbid conditions: https://twitter.com/AstraZenecaUS/status/1010526644656799744

Transplants:
https://twitter.com/drpratikc/status/1011353557013073920
An attempt at a head-to-head comparison of islet transplants vs. Artificial Pancreas results.  Interesting!

The other form of bihormonal AP:
https://twitter.com/EndocrineToday/status/1011330691009658880
Most bihormonal AP research uses insulin and glucagon, but this one uses insulin and pramlintide.

Faustman:
News: https://www.healthline.com/diabetesmine/denise-faustman-research-pushback-ada-jdrf?platform=hootsuite
Discussion: https://twitter.com/Drbeth_/status/1010431411671748608
Poster and Discussion: https://twitter.com/HangryPancreas/status/1011294476260831233
ADA and JDCA joint letter (later supported by the Berrie Center):
    https://twitter.com/keddy_moise/status/1011420460612030464
    https://twitter.com/DiabetesMine/status/1011400346441220096
    https://twitter.com/JDRF/status/1011399303665995776
    https://twitter.com/nbdiabetes/status/1011640607259930625
These two guys (and many others) report dropping A1c, but no one calls them a cure:
    https://twitter.com/snp_io/status/1010616966523088896
    https://twitter.com/Fallabel/status/1011280750967246848

Interesting to me:
Open Data Tools for Software Nerds: https://twitter.com/stales/status/1010599135576231936
I found the next tweet interesting because Cure was in title, but treatment in contents.  To me that shows a problem with "cure" research.  Much of it is not really aimed at a cure:
https://twitter.com/DanielJDrucker/status/1010870015183278080
TEDDY:
    https://twitter.com/cristinatejerap/status/1010586167102922752
    https://twitter.com/ERobertson02/status/1010614817244286976
    https://www.healio.com/endocrinology/diabetes/news/online/%7B78982aaa-a6f8-4b1f-a74b-04e3bc6e760a%7D/insights-from-teddy-study-provide-clues-to-islet-autoimmunity-in-children

Low Carb:
https://twitter.com/DikemanDave/status/1011393166849728512
https://twitter.com/JPMcCarter/status/1011328194115522560
https://www.diabetesdaily.com/blog/very-low-carbohydrate-diets-for-diabetes-ada-2018-580309/?utm_campaign=coschedule&utm_source=twitter&utm_medium=diabetesdaily&utm_content=Very%20Low%20Carbohydrate%20Diets%20for%20Diabetes%20(ADA%202018)
https://twitter.com/JPMcCarter/status/1011697843260837888
https://www.linkedin.com/feed/update/urn:li:activity:6417463469972430848/

Atkinson honored (nPOD and much more):
https://twitter.com/_HealthMyself/status/1011262077191716864
https://twitter.com/HIRN_CC/status/1011255219202633728

The "Most Obvious Research Conclusion Award"
https://twitter.com/DrKirstieBell/status/1010881942974291968

Joshua Levy 
http://cureresearch4type1diabetes.blogspot.com 
publicjoshualevy at gmail dot com 
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF, JDCA, or Bigfoot Biomedical news, views, policies or opinions. In my day job, I work in software for Bigfoot Biomedical. My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.

Sunday, June 24, 2018

Alpha Difluoromethylornithine (DFMO) Starts A Phase-II? Trial in Honeymoon Type-1 Diabetics

This trial started recruiting in April 2015, but I missed it at that time, so I'm blogging about it now.

Alpha Difluoromethylornithine (DFMO) is approved for two quite different issues.  The first is to remove/prevent facial hair in women, while the second is to treat sleeping sickness.  Neither of these are related to type-1 diabetes.   However, this drug was effective in lowering diabetes rates in NOD mice (which are predisposed to an autoimmune diabetes, similar to human type-1 diabetes), and that is what motivated this trial.

The Trial

This trial is recruiting people 12-40 years old, who have been diagnosed with type-1 diabetes in the last 2-8 months.  People will be divided up into 4 different groups, each getting a different dose.  Within each dose group, there will be 6 people who get the treatment and 3 people who get a placebo (and will be a control group).

Primary endpoints are safety related, while other endpoints (such as C-peptide) are targeted at seeing if it works.

The researchers hope to finish gathering data in Dec 2019, so publication should be some time in 2020.  (Although the primary outcome data will be collected in Dec 2018, so there is the possibility of partial results in 2019.)

This trial is being run in three locations:

Riley Hospital for Children: Indianapolis, Indiana, United States, 46202
Contact: Stephanie Woerner, FNP    317-944-2573    sestein@iu.edu 

Women and Children's Hospital of Buffalo: Buffalo, New York, United States, 14222
Contact: Michelle Ecker, RD, CDN, CDE    716-878-7609    mecker@upa.chob.edu 
       
Children's Hospital of Wisconsin: Wauwatosa, Wisconsin, United States, 53226
Contact: Joanna Kramer, CCRC    414-955-8486    jkramer@mcw.edu 


Discussion

Although listed as a Phase-I trial, in some ways it is more like a phase-II study, which is why I've listed it as a Phase-II? study.  The question mark signifies that this drug has never been tested on people with type-1 diabetes before.  I consider it Phase-II because it is the right size (42 people) and the right purpose (testing multiple different doses) to be a Phase-II study.

Clinical Trial Record: https://clinicaltrials.gov/ct2/show/NCT02384889
Results in mice: https://www.ncbi.nlm.nih.gov/pubmed/23846959

Personal Note

I am always surprised how much researching type-1 diabetes teaches me about other subjects.  One part of the story of DFMO is both fascinating and horrifying.  After being developed in the 1990s, it was used intravenously as a treatment for sleeping sickness.  However, in 1995 production was discontinued, because saving lives in Africa was not profitable. Various non-profits lobbied the producer (a big pharma firm) to restart production, but to no avail.  Meanwhile, researchers discovered that it "cured" facial hair in women.  The cream used to do this went into production in 2000, and has been on the market since then.   Under intense pressure from the World Health Organization and non profits, the big pharma company eventually agreed to provide the drug for free to non-profits for distribution to African sleeping sickness patients, starting in 2001.  My best guess is that the lack of drug between about 1995 and 2001 killed between 40,000 and 110,00 people (very roughly).

The key moment in making the drug available may well have been a "60 Minutes" episode.  This is an American weekly news show.  It showed patients dying of sleeping sickness, or enduring painful IV treatments, which was the best non-DFMO drug available, and then followed it up with DFMO's American TV add for removing facial hair.  The juxtaposition highlighted the money-at-the-cost-of-lives reality of the situation.

Joshua Levy
http://cureresearch4type1diabetes.blogspot.com
publicjoshualevy at gmail dot com
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF, JDCA, or Bigfoot Biomedical news, views, policies or opinions.  In my day job, I work in software for Bigfoot Biomedical.  My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.

Tuesday, June 12, 2018

GNbAC1 Starts A Phase-II? Trial


GNbAC1 is a monoclonal antibody which has completed phase-II testing for treating Multiple Sclerosis, which (like type-1) is an autoimmune disease.  GNbAC1 was developed by GeNeuro SA, a Swiss company, but is being tested in Australia.   They have partnered with Servier, a large French pharma company to do the phase-III trials required to bring it to the Multiple Sclerosis market.

A monoclonal antibody is an artificially created antibody which targets one very specific type of cell in the body.  Different monoclonal antibodies target different types of cells.  So if a disease is caused by a problem in one type of cell, then using a monoclonal antibody to target that type of cell is a promising treatment.  Because several monoclonal antibodies have been successful in treating other autoimmune diseases, they are an active area of research for curing type-1 diabetes.

Previously, GNbAC1 has been tested in four clinical trials as part of the Multiple Sclerosis development program, so its safety is well established (for an investigational drug).  However, since this is the first trial aimed at type-1 diabetes, I'm calling it a "Phase-II?" trial.  (The question mark meaning "no previous testing on people with type-1".)

This Study

This study has enrolled 60 people who were diagnosed with type-1 diabetes within the last 4 year.  The first part will be double blind, with 2/3s getting the treatment and 1/3 not.  After that will be a second, optional part which is not blinded (everyone will get the treatment).  Unfortunately, the primary end point for this trial is safety related.  But their press release does say that they will track various effectiveness outcomes as well (for example: C-peptide and insulin consumption).  The drug will be given as an IV drip once a month (six doses in each part of the study).  People in the study will be followed for about a year.

This study completed enrollment in January 2018, and GeNeuro plans to publish the results from the first part of the trial in September 2018, and the second part of the trial in the first half of 2019.  That is pretty quick!

Press Release: http://www.geneuro.com/data/news/GeNeuro-TD1-Study-Enrollment-Complete.pdf
Clinical Trial Registry: https://clinicaltrials.gov/ct2/show/NCT03179423
Company: http://www.geneuro.com/
General Background News Article: http://www.biotuesdays.com/features/2017/11/16/geneuro-pioneering-hervs-against-neurodegenerative-and-autoimmune-diseasess

MS research:
● http://www.msdiscovery.org/research-resources/drug-pipeline/10103-gnbac1
● https://www.ncbi.nlm.nih.gov/pubmed/25392325

Background and Rational

This clinical trial has a very different rational, as compared to previous attempts to cure type-1 with monoclonal antibodies.  In the past, these antibodies have been used to target one of the defective cell types within the immune system.  The idea is to find an immune cell which is involved in the attack on the beta cells, and kill off those immune cells.  That idea has led to some progress, some suggestive results, but nothing like a cure.

These researchers have a different idea.  They note that part of the human genome contains HERVs, which are the remains of retroviral DNA which merged into our DNA millions of years ago.  The researchers believe that while this DNA does nothing most of the time, infection can sometimes cause one of these HERVs (called "pHERV-W") to activate and generate a protein (called "pHERV-W env") used by the retrovirus the DNA came from originally.  Even after the infection, the HERV DNA stays activated.  The pHERV-W env, in turn, causes autoimmune diseases.  If true, this would explain how viral infections can "trigger" type-1 diabetes.

These researchers believe that by using a monoclonal antibody to target pHERV-W, they can stop this process.   So while previous attempts to use monoclonal antibodies targeted malfunctioning immune cells, this attempt is targeting HERV DNA which (according to this theory) is the root cause of the autoimmunity.

Background reading: https://en.wikipedia.org/wiki/Endogenous_retrovirus


Joshua Levy 
http://cureresearch4type1diabetes.blogspot.com 
publicjoshualevy at gmail dot com
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.