Peru "pill mill" doctor enters into plea agreement with no prison time

50 felony charges would be dropped against Tristan Stonger

Carson Gerber
Nov 2, 2017

PERU – A Peru pain doctor who was arrested on 55 felony charges in connection to operating a “pill mill” has entered into a plea agreement in which he would serve over 10 years on probation, but no prison time.

Dr. Tristan Stonger, who lives near Bunker Hill, operated Pain Management Centers of Indiana, which had offices in Peru, Bloomington and Indianapolis. Prosecutors say his headquarters were located in Peru.

Stonger, 70, was arrested in January after a three-year investigation by agents with the U.S. Drug Enforcement Agency, who spent months surveilling Stonger’s Peru clinic located at 1 S. Broadway St.

On Thursday, he appeared before Miami County Circuit Court Judge Tim Spahr to enter into an agreement with prosecutors, in which he pleaded guilty to five of the charges in exchange for the remaining 50 charges being dropped.

The charges to which he pleaded guilty include possession of a narcotic drug, two counts of issuing an invalid prescription for legend drugs, insurance fraud and Medicaid fraud.

The agreement calls for a 10-and-a-half-year sentence to be served as supervised probation. The agreement would also prohibit Stonger from applying for any medical license in Indiana, or any license or permit from the Drug Enforcement Administration.

Judge Spahr has taken the agreement under advisement and will either accept or reject it during a hearing set for Nov. 30.

Miami County Prosecutor Bruce Embrey said he felt the plea agreement was appropriate considering Stonger’s age and the fact the courts have seized all his assets following his arrest.

“We’ve got a 70-year old doctor who was not able to do much, if any, prison time if this went to trial,” Embry said. “We’re taking his livelihood, we’re taking his property and we’re taking his license. He’ll have to find some other way to live.”

Stonger also faces charges in Indianapolis and Bloomington, where he operated branches of his clinic. Embrey said prosecutors involved in those two cases have agreed any additional convictions in their cases would not add time to the sentence set in the plea agreement in Miami County.

The court hearing Thursday comes after investigators say a former employee said Stonger had a number of “back door” patients who didn’t have to wait to see him, despite his other patients waiting sometimes three hours for their appointments, according to court documents.

At least two patients told investigators they were employed by Stronger at his farm near Bunker Hill, where they worked on his vehicles or fed animals in exchange for payment for their pills.


Agents also identified two patients who died from overdoses after Stonger refilled their prescriptions.

The son of one victim, who died in Howard County, told investigators Stonger knew he was treating drug-addicted patients and did not prescribe pills for legitimate medical issues.

The son said Stonger “knows how to get away with it” and called the Peru clinic “just a legal dopehouse,” according to the affidavit.

Carson Gerber can be reached at 765-854-6739, carson.gerber@kokomotribune.com or on Twitter @carsongerber1.

http://www.kokomotribune.com/news/peru-pill-mill-doctor-enters-into-plea-agreement-with-no/article_6fd7d7be-c000-11e7-b6db-d31e9614bc8b.html

Acyclovir and Wellcome/Glaxo

Acyclovir (Zovirax) 

Acyclovir in Brief

• Generic name: Acyclovir (acycloguanosine)
• Brand names: Zovirax®
• Therapeutic class: Antiviral
• Pharmacologic class: Acyclic purine nucleoside analogue
• FDA Approved:
  Ointment: March 29, 1982
  Injection: October 22, 1982
  Capsules: January 25, 1985
  Tablets: April 30, 1991
• Pregnancy Category: B
• Originally discovered: 1974, USA 

History

Acyclovir was the first successful antiviral agent in the world. It was originally synthesized in 1974 by Howard Schaeffer at Wellcome Research Laboratories (now GlaxoSmithKline). After Schaeffer's discovery, Gertrude B. Elion and her team went to work, studying how the drug worked, why it worked, and why it was so nontoxic. They detected that acyclovir remains inert until it meets the herpes virus.

For four years, from 1974 to 1977, more than seventy-five researchers kept acyclovir secret. The first report detailing the selective antiviral activity of acyclovir against herpes viruses was published in 1977 2.

Acyclovir got FDA approval and was released commercially in 1982. It was marked under the trade name Zovirax by the Burroughs Wellcome Company. The original formulation was a topical ointment. Acyclovir became available in oral formulation (200 mg capsules) in 1985 6.

FDA approved uses

• Oral
• Initial genital herpes
• Recurrent genital herpes
• Herpes zoster infections (shingles)
• Chickenpox (varicella)
• Topical
• Recurrent herpes labialis (cold sores)
• Parenteral
• Herpes simplex, mucosal and cutaneous
• Severe initial episodes of genital herpes
• Herpes simplex encephalitis
• Neonatal herpes simplex infection
• Varicella-zoster (shingles) infections

Off-label & Investigational uses

• Prevention of HSV-2 transmission 13
• Cytomegalovirus infection and disease after organ transplantation 9
• Herpes simplex virus infection after organ transplantation 10,11
• Ocular herpes simplex 15
• Herpes zoster ophthalmicus 17
• Varicella pneumonia16
• Infectious mononucleosis 4
• Reduces the need for cesarean delivery for recurrent herpes in women whose first clinical episode of genital herpes occurred during pregnancy 18.
• Herpetic gingivostomatitis 5

Spectrum of activity

Acyclovir exhibits activity against four of the five major herpes-group viruses:

• Herpes simplex virus type 1 (HSV-1) 7
• Herpes simplex virus type 2 (HSV-2) 7
• Varicella zoster virus (VZV) 7
• Epstein-Barr virus (EBV)5, 7
• Cytomegalovirus (CMV) (poor activity) 7, 8

Acyclovir is most active against HSV-1 followed by HSV-2 19. Its activity against VZV also is considerable but ten-fold less.

Acyclovir "pros" and "cons"

Advantages:

• High efficacy against HSV and VZV infections
• Very effective for the suppression of recurrent genital herpes, a sexually transmitted infection. Acyclovir reduces recurrence by about 90%.
• Excellent clinical safety profile 6 -- aside from drug hypersensitivity, there are no absolute contraindications to acyclovir
• Safe during pregnancy -- although there are no large, controlled studies of acyclovir safety in pregnant women, a prospective epidemiological registry of acyclovir use during pregnancy showed no increase in the incidence of birth defects.
• Continuous suppressive therapy with acyclovir has been shown to be safe for as long as 5-10 years.
• Minimal toxicity - acyclovir cannot interfere with DNA synthesis in cells that are not infected with the virus
• Well-tolerated by most patients
• Highly effective for suppression of HSV shedding 13, 14
• Minor risk of drug interactions
• Inexpensive

Disadvantages:

• The main weakness of acyclovir is its low oral bioavailability due to low water solubility -- only 15-30% of an oral dose is absorbed. Also, bioavailability decreases with increasing dose. Liquid formulation has lower oral bioavailability.
• Inconvenient frequent dosing regimen (4-5 times) because of the short half-life of less than 4 hours.
• Risk of renal failure and nephrotoxicity12 due to crystallization of acyclovir sodium following parenteral administration.
• Does not eradicate latent virus.

Mode of action

Acyclovir is a synthetic purine nucleoside analogue with inhibitory activity against herpes simplex virus types 1, 2, and varicella-zoster virus. In simple words, it is so similar to substance that the herpes virus needs for reproduction that the virus is deceived and commits suicide.

The inhibitory activity of Acyclovir is highly selective. It is converted to acyclovir monophosphate by virus-specific enzymes thymidine kinase then further converted to acyclovir triphosphate by other cellular enzymes.

Acyclovir triphosphate stops replication of herpes viral DNA. This is accomplished in 3 ways: 1) competitive inhibition of viral DNA polymerase, 2) incorporation into and termination of the growing viral DNA chain, and 3) inactivation of the viral DNA polymerase.

The greater antiviral activity of Acyclovir against HSV compared to VZV is due to its more efficient phosphorylation by the viral thymidine kinase.

Time to clear out of the system

The half-life of acyclovir is 3 to 4 hours in people with normal kidney function and up to 20 hours in those with renal impairment.

Further reading

• Acyclovir (Zovirax) versus...
• Acyclovir vs Valacyclovir

References

• 1. Physicians’ Desk Reference, 54th ed; Medical Economics, Thomson Healthcare: Montvale, NJ; 2000.
• 2. Elion, G. B., P. A. Furman, J. A. Fyfe, P. de Miranda, L. Beauchamp, and H. J. Shaeffer. 1977. Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl)guanine. Proc. Natl. Acad. Sci. USA 74:5716-5720.
• 3. Darby, G. 1995. In search of the perfect antiviral. Antiviral Chem. Chemother. 6(Suppl. 1):54-63.
• 4. Torre D, Tambini R. Acyclovir for treatment of infectious mononucleosis: a meta-analysis. Scand J Infect Dis. 1999;31(6):543-7.
• 5. Nasser M, Fedorowicz Z, Khoshnevisan MH, Shahiri Tabarestani M. Acyclovir for treating primary herpetic gingivostomatitis. Cochrane Database Syst Rev. 2008 Oct 8;(4)
• 6. Tilson HH, Engle CR, Andrews EB. Safety of acyclovir: a summary of the first 10 years experience. J Med Virol. 1993;Suppl 1:67-73. PubMed
• 7. Collins P. The spectrum of antiviral activities of acyclovir in vitro and in vivo. J Antimicrob Chemother. 1983 Sep;12 Suppl B:19-27.
• 8. Freitas VR, Smee DF, Chernow M, Boehme R, Matthews TR. Activity of 9-(1,3-dihydroxy-2-propoxymethyl)guanine compared with that of acyclovir against human, monkey, and rodent cytomegaloviruses. Antimicrob Agents Chemother.1985 Aug;28(2):240-5.
• 9. Legendre C, Ducloux D, Ferroni A, Chkoff N, Geffrier C, Rouzioux C, Kreis H. Acyclovir in preventing cytomegalovirus infection in kidney transplant recipients: a case-controlled study. J Med Virol. 1993;Suppl 1:118-22. PubMed
• 10. Lundgren G, Wilczek H, Lönnqvist B, Lindholm A, Wahren B, Ringdén O. Acyclovir prophylaxis in bone marrow transplant recipients. Scand J Infect Dis Suppl. 1985;47:137-44. PubMed
• 11. Pettersson E, Eklund B, Hockerstedt K, Salmela K, Ahonen J. Acyclovir and renal transplantation. Scand J Infect Dis Suppl. 1985;47:145-8. PubMed
• 12. Lam NN, Weir MA, Yao Z, Blake PG, Beyea MM, Gomes T, Gandhi S, Mamdani M, Wald R, Parikh CR, Hackam DG, Garg AX. Risk of acute kidney injury from oral acyclovir: a population-based study. Am J Kidney Dis. 2013 May;61(5):723-9.
• 13. Wald A, Zeh J, Barnum G, Davis LG, Corey L. Suppression of subclinical shedding of herpes simplex virus type 2 with acyclovir. Ann Intern Med. 1996 Jan 1;124(1 Pt 1):8-15. PubMed
• 14. Sheffield JS, Hollier LM, Hill JB, Stuart GS, Wendel GD. Obstet Gynecol. 2003 Dec;102(6):1396-403. PubMed
• 15. Oral acyclovir for herpes simplex virus eye disease: prevention of epithelial keratitis and stromal keratitis. Herpetic Eye Disease Study Group. Arch Ophthalmol. 2000 Aug;118(8):1030-6. PubMed
• 16. El-Daher N, Magnussen R, Betts RF. Varicella pneumonitis: clinical presentation and experience with acyclovir treatment in immunocompetent adults. Int J Infect Dis. 1998 Jan-Mar;2(3):147-51. PubMed
• 17. Hoang-Xuan T, Büchi ER, Herbort CP, Denis J, Frot P, Thénault S, Pouliquen Y. Oral acyclovir for herpes zoster ophthalmicus. Ophthalmology. 1992 Jul;99(7):1062-70 PubMed
• 18. Scott LL, Sanchez PJ, Jackson GL, Zeray F, Wendel GD Jr. Acyclovir suppression to prevent cesarean delivery after first-episode genital herpes. Obstet Gynecol. 1996 Jan;87(1):69-73.
• 19. K. D. Tripathi. Essentials of Medical Pharmacology. 7th Ed, Jaypee Brothers Medical Publishers 2013.

Published: March 31, 2008
Last reviewed: July 14, 2017

http://www.emedexpert.com/facts/acyclovir-facts.shtml

UK company wins global medicine award for its ground-breaking potential MS treatment

A leading scientist battling to halt the development of Multiple Sclerosis has revealed that clinical human trials will start by 2020, after her company was honoured with a major nano medicine award. Dr Su Metcalfe's regenerative nanomedicine company, LIFNano™, was named Most Promising Nanomedicine Project at the International Nano Medicine Awards in Berlin on Tuesday, November 7.

Founded by Dr. Metcalfe, LIFNano™ slowly releases nanoparticles which are forecast to trigger natural healing in the brain. They contain Leukaemia Inhibitory Factor (LIF), to counter the disease process as it attacks the brain and spinal cord.

Dr. Metcalfe, who earned a PhD in pathology at the University of Cambridge, launched the technology company LIFNano™in 2013 and has been recognised many times already in the last few years. She said, upon receiving this global award “It has always been about getting this to patients. We have found evidence in our animal trials showing significant healing of damaged brain tissue in addition to the potent protection of brain cells.” Dr Metcalfe, who is based in Cambridge, England went on to say, “We are honoured to have been selected for this international award, but our absolute focus is ensuring patients see the benefits through clinical trials in 2020.”

Dr. Su. Metcalfe (middle), picking up the Most Promising Nanomedicine Project at the International Nano Medicine Awards in Berlin on Tuesday, November 7.

Battling with Multiple Sclerosis

Multiple sclerosis (MS), is a neurological disease that attacks the brain and spinal cord. It affects more than 2.3 million people around the world and occurs when the immune system attacks the myelin sheath, the protective coating that encases nerve cells. This triggers symptoms such as vision problems, poor balance and muscle spasms. It could lead to total disability and dementia. The disease is forecast to cost in excess of $100 billion annually around the globe.

The issue with current treatments has been that they typically greatly diminish the activity of immune cells and they need to be used on a regular basis. Although these treatments prevent those immune cells from ravaging myelin within the brain, they also leave the body vulnerable to infection. None protects the brain. Metcalfe’s nanoparticles reset and correct the fault that causes MS as they deliver the natural stem cell growth factor LIF, directly and specifically to the sites of nerve damage, and keep the immune system from attacking myelin. They do not impair immunity and allow immune cellsto mobilize against harmful invaders when needed. What’s more, LIF can actually help repair damaged myelin within the brain.

If LIFNano™ holds up in clinical trials, “that would be a really significant addition to the treatments we have,” explained Bruce Bebo, executive vice president of research at the National Multiple Sclerosis Society, in an interview in October with OZY. Another benefit is its targeted approach which means fewer side effects expected, using the naturally occurring LIF.

For patients with MS, the potential of LIFNano™ could be profound once clinical trials have been successfully completed. Indeed, in addition to regulating immunity, a further key role of LIF is to sustain a healthy central nervous system, protecting nerves and maintaining myelin. LIFNano is therefore a powerful candidate for treatment of patients suffering from MS, providing a triple action for healing the brain and protecting nerves, repairing myelin and resettingself-tolerance. The beauty of the technology is its simplicity as it lets the body do what nature intended, slowly releasing LIF via the nanoparticles. Time really matters for MS sufferers, as early treatment is known to slow the course of the disease.

Dr Metcalfe's preclinical research has already found no toxicity of the LIF nanoparticles. Remarkably, LIF itself, the PLGA nanoparticles, as well as the anti-body fragment used to direct them have all been already used, separately, in various clinical trials. 

Quantum Leap Nanomedicine

The nanoparticle manufacture has originally been developed jointly by Dr. Metcalfe and Yale University. Ultimately, Yale granted an exclusive license to LIFNano™ to develop the platform for MS, and for other degenerative diseases such as dementia and for auto-immune conditions, for years to come. The company, which has been self-funded to date, uses safe and natural ingredients rather than synthetic drugs.

LIFNano™ has a stellar team and advisers who are now working with Dr Metcalfe, including its Chairman, Florian Kemmerich, who also heads up the Europe-based NanoMed. The company's CEO, Olivier Jarry, joined the company with executive experience at Novartis, Bayer and Bristol-Myers Squibb, in addition to having consulted for giants such as Pfizer, GSK and Sanofi. Commenting on the award Olivier said, “Our treatment has the curative potential to deal with the root cause of MS, rather than just addressing symptoms and we hope to prove this in our human trials.” He went on to say, “the delivery of LIF across the blood brain barrier could profoundly improve therapeutic outcomes, reducing costs and potentially increasing convenience and safety.”

The Chairman of the company, Florian Kemmerich, said, “We have great partners, solid patents and exclusive licenses. This platform technology could go on to have profound impacts on other diseases such as Alzheimer's. We have received a lot of support and more is coming due to the scalability of the platform. We believe that, by successfully delivering these LIF nanoparticles to the brain, we will enable cells damaged by 'rogue' white blood cells to be repaired. This should then re-balance the body, using the natural reparative immune system we all have.”

The EU's European Technology Platform Awards honour firms that have developed a nanomedicine solution “that could bring significant benefits to patients, changing the way diseases are treated or diagnosed or providing new tools for physicians.” It further supports our drive to reach people with MS quickly. The award has previously been won by the Merck group, for a project aiming to develop a nanomedicine oncology product for mucosal therapeutic vaccination.

LIFNano™ and Dr. Metcalfe can add this to several other awards they have won or have been shortlisted for, including the UK government-backed Innovate UK Smart Award, the Merck Serono GMSI award, the Rolex Award for Enterprise and Business Weekly's Woman Entrepreneur of the Year Award.

The company is currently securing investment to complete GMP manufacturing, and secure authorizations to start clinical trials, aiming at generating a ‘proof of concept’ (Phase IIa) in 2020.

To contact the company or to find out more about the technology go to www.lifnano.com or contact investor-relations@lifnano.com

https://nano-magazine.com/news/2017/11/7/uk-company-wins-global-medicine-award-for-its-ground-breaking-potential-ms-treatment/?email=donpatent@gmail.com

Targeting a single protein might treat a broad range of viruses

November 8, 2017

The measles virus is suppressed (right) when a key protein, SPCA1, is decreased in the host. Credit: Hans-Heinrich Hoffmann

Most drugs that fight viruses are designed to target individual pathogens. But scientists at The Rockefeller University have identified a protein that a broad range of viruses require to spread within a host—a discovery that could lead to fighting viruses as varied as parainfluenza, West Nile, and Zika with a single drug.

All viruses use proteins from the host's cellsin order to replicate. A team in Charles M. Rice's lab has identified a calcium-transporting protein that is needed by many viruses during the later stages of their life cycles. The researchers showed that depleting this protein in host cells significantly impairs the viruses' ability to spread, without harming the cells.

By indicating a way that a single medicine could fight many infections, these advances have the potential to multiply the return on time and effort invested in drug development. The researchers' findings were reported this month in Cell Host & Microbe.

"There's been a push to get broader antivirals, and that's difficult because viruses tend to be very different in what they do, exactly," says Hans-Heinrich Hoffmann, the lead author of the study. "The key to creating a broad antiviral medicine is to find a host protein that many viruses need but that is not essential to the cell's survival. And that's exactly what we found here."

From RSV to Zika

The researchers launched their study by trying to find a host protein required by the human respiratory syncytial virus (RSV), a major virus that is particularly dangerous to children and the elderly, causing an estimated 3.4 million hospitalizations a year. There are currently no vaccines against RSV or specific antivirals that fight it.

Even a partial loss of the protein, the calcium pump SPCA1, limited the ability of many viruses to mature and spread, the scientists found. Cells that lack the protein were also less susceptible to initial infection.

After finding that RSV requires SPCA1, the researchers determined that many other viruses, both insect-borne and respiratory, need the protein. Among those is Zika, the mosquito-borne virus linked to brain malformation in infants. As with RSV, there are no approved antivirals for Zika.

Patients lacking proteins

It is one thing to study whether individual cells can survive without a protein. But to be useful as a therapy, researchers would need to understand how a lack of SPCA1 affects an entire organism—such as an actual patient.

There are, in fact, individuals who have reduced levels of SPCA1, as a result of a rare genetic disorder known as Hailey-Hailey disease. The disease causes skin problems, such as blisters and lesions, but is not life-threatening. Furthermore, cell cultures derived from patients with Hailey-Hailey disease indicate that their cells are less susceptible to certain infections, including RSV—a result that correlates with the researchers' other findings.

"We know that these patients get by with only half the normal amount of the protein, and we have evidence that this may even offer a protective effect," says Rice, who is the Maurice R. and Corinne P. Greenberg Professor in Virology and head of the Laboratory is Virology and Infectious Disease. "It's a promising avenue for drug development."

Explore further: 'Exciting' discovery on path to develop new type of vaccine to treat global viruses

More information: H.-Heinrich Hof Diverse Viruses Require the Calcium Transporter SPCA1 for Maturation and Spread, Cell Host & Microbe (2017). DOI: 10.1016/j.chom.2017.09.002

Journal reference: Cell Host & Microbe

Provided by: Rockefeller University

Read more at: https://phys.org/news/2017-11-protein-broad-range-viruses.html#jCp