Genetically modified virus saves teen's life, offers hope in fight against antibiotic resistance

A treatment using a genetically modified virus is offering hope in one teen's battle against cystic fibrosis and antibiotic-resistant bacteria. CNN's Phil Black reports.

Posted: May 11, 2019 3:00 AM
Updated: May 11, 2019 3:00 AM

Isabelle Carnell-Holdaway, 17, has faced not one but two unrelenting threats to her life. Diagnosed at 11 months of age with cystic fibrosis, the progressive genetic disease that causes lung infections and breathing impairment, Isabelle has also combated an on-again, off-again infection caused by antibiotic-resistant bacteria since age 8.

"Children with cystic fibrosis are very prone to picking up all sorts of nasty infections," said her mother, Jo Carnell-Holdaway.

By the time she was 14, Isabelle's lung function was about 25% or 30%, according to her mother. In September 2017, at 15, she underwent a double lung transplant, as recommended by her doctor Dr. Helen Spencer, a respiratory pediatrician and lead for the lung transplant service at Great Ormond Street Hospital in London.

Though the operation was "uncomplicated," luck was not on Isabelle's side in the days after the procedure, according to a case study published Wednesday in the journal Nature Medicine that describes a first-of-its-kind experimental treatment.

When her doctors discontinued the intravenous antibiotics that caused Isabelle severe side effects, the bacterial infection that had plagued her for years returned with a vengeance. Her surgical incisions turned vibrant red.

By January 2018, "her liver really started to fail," and Isabelle ended up back in the intensive care unit with acute liver failure, he mother said.

Spencer described her prognosis at this point as "very poor."

"I know that because of the experience that I've had with other patients who have had a transplant and who were infected with MB," Spencer said. "All of those patients went on and died."

MB, or Mycobacterium abscessus, the bacterium causing Isabelle's infection, is a type of antibiotic-resistant bug that, though commonly found in nature, does not usually cause sickness in healthy people.

One of the hospital consultants told Isabelle's mother that her daughter wouldn't be leaving and gave Isabelle "less than 1% chance of survival," Carnell-Holdaway said. "We were totally devastated by that."

Dire circumstances led Spencer to consider experimental treatments for the teen, which resulted in a cocktail of genetically engineered viruses that altered the course of Isabelle's recovery.

"It was actually the patient's mum, Jo, who asked me about phage therapy," she said.

Creating a one-of-a-kind treatment

Bacteriophages or "phages" are viruses that can infect and destroy bacteria. The natural enemy of bacteria, phages are ubiquitous on Earth -- found in soil and seawater -- and in our own guts.

"Cocktails of phages were used therapeutically in Europe and the United States during the pre-antibiotic era, and they are still prevalent in Russia and Central and Eastern Europe today, for wound infections, gastroenteritis, sepsis and other ailments," wrote Charles Schmidt, a science writer, in a related article published in the journal Nature Biotechnology. "In the West, phage therapy was abandoned after broad-spectrum antibiotics came on the scene."

Luckily, Spencer said, "one of our microbiologist consultants here did his thesis on phage therapy 20 years ago." Offering advice on Isabelle's case, "he, by chance, knew a phage scientist in the [United] States, Graham Hatfull."

A conference call between Spencer's and Hatfull's teams included Robert Schooley, an infectious-disease specialist who heads a phage translational research center at the University of California, San Diego, who "happened to be visiting Graham on the same day, so he came in on that same conversation."

"We sent a sample of our patient's bacteria over to that lab, and Graham and his team did an amazing job finding the phages that would kill her bacteria," Spence said.

To create a phage therapy, it is necessary to correctly characterize phage biology and the genetic interactions that will occur between the phage and the target bacterium -- no easy feat, according to Schmidt, who notes that the function of as much as 90% of the phage genome remains unknown. "Despite the fact that phage have been a subject of research for nearly a century, very little is known about them," he wrote.

Additionally, the creation of Isabelle's therapy, which combined three separate phages, required Hatfull and his team to genetically engineer one of the phages to more efficiently kill the target bacterium.

Isabelle's experience with the treatment

When Isabelle was sent home from the hospital in April 2018, she was "not eating, had severe weight loss, had abnormal liver function and skin nodules were popping up -- one or two every week," Spencer said.

Isabelle had spent months in bed and lacked strength, her mother recalled: "We were doing everything for her. She had to be carried here; she had to be carried to the toilet; she had to be carried to bed. She just could not walk."

About two months after returning home, Isabelle was given her first dose of phage treatment, both intravenously and applied directly to her wounds, while continuing on IV antibiotics and the usual course of immunosuppressive drugs that are necessary to prevent rejection of a transplanted organ.

Spencer said that "a big lesion" by Isabelle's liver "disappeared, and then we've seen the wounds on the skin just gradually -- gradually -- just slowly start to heal."

Her mother noted that "within weeks, this amazing treatment from Mother Nature was having this incredible effect on her body. Her appetite improved. She's had weight gain."

Isabelle also returned to school in September and, for the first time in her life, has been attending classes "every single day with no problems, no issues, at all," her mother added. "She's just loving her life. And she's even got herself a Saturday job, starting this weekend."

Spencer is also hopeful, if more guarded: "We are dealing with microbacterium, and in treating it, we know this is a long game; it's not a short fix. I think we're looking at several more months, if not years, of treatment for her.

"We haven't cured her," Spencer said, adding that that today, 11 months since the start of Isabelle's treatment, the bacterium is still causing skin lesions "on occasion. I hope with time, eventually, she'll clear the infection. If it will happen or not, I don't know."

The future of phages

While the therapeutic use of phages remained largely unexplored for decades, the field "sputtered back to life" in the early 2000s due, in part, to "the rise of modern sequencing technology," Schmidt wrote.

Hatfull, a professor of biotechnology at the University of Pittsburgh, believes that this accomplishment "represents a number of firsts: the first genetically engineered phage treatment ... and the first treatment of a mycobacterium," Schmidt said. The proof-of-concept treatment, he noted, also bodes well for "the future of synthetic-biology approaches to the vexing problem of antibiotic-resistant bacteria."

Schmidt notes that pharmaceutical companies, including Johnson & Johnson, have begun to invest in potential phage therapeutics, while scientists believe the field is better positioned today with faster, cheaper genetic screening and greater understanding of phage pharmacology. Still, production costs "pose a major hurdle," and much remains unknown about phage biology.

"Even as companies move toward clinical trials, they're confronting entrenched biases against phage therapy by physicians inclined to view it as an old Soviet technology that was never backed by reliable evidence," he wrote.

Terre Haute
Cloudy
53° wxIcon
Hi: 53° Lo: 48°
Feels Like: 53°
Robinson
Cloudy
52° wxIcon
Hi: 54° Lo: 47°
Feels Like: 52°
Indianapolis
Cloudy
53° wxIcon
Hi: 54° Lo: 48°
Feels Like: 53°
Rockville
Cloudy
51° wxIcon
Hi: 53° Lo: 48°
Feels Like: 51°
Casey
Cloudy
52° wxIcon
Hi: 53° Lo: 47°
Feels Like: 52°
Brazil
Cloudy
53° wxIcon
Hi: 53° Lo: 48°
Feels Like: 53°
Marshall
Cloudy
53° wxIcon
Hi: 52° Lo: 47°
Feels Like: 53°
Becoming cloudy, Thursday Showers
WTHI Planner
WTHI Temps
WTHI Radar

Latest Video

Image

Vermillion County Jail Update

Image

Thursday: Showers, cooler. High: 57

Image

All You Need to Know for Thursday

Image

Parke Heritage FB

Image

Local Restaurant Faces Shortages

Image

Local Restaurant Faces Shortages

Image

Northview football

Image

ABORTION ACT

Image

A cleanup is underway for a blighted property in West Terre Haute

Image

Kevin takes a look at your trick or treating forecast

WTHI Events

 

Illinois Coronavirus Cases

(Widget updates once daily at 7 p.m. CT)

Cases: 1690274

Reported Deaths: 28140
CountyCasesDeaths
Cook63944711255
DuPage1093201384
Will920761135
Lake807921092
Kane68965881
Winnebago41587561
Madison40362602
St. Clair36458602
McHenry35137334
Champaign27218198
Peoria27092370
Sangamon25942288
McLean23232222
Tazewell20771333
Rock Island19009365
Kankakee18051253
Kendall16376115
Macon15416253
LaSalle15144288
Vermilion14595202
Adams13266154
DeKalb12273134
Williamson12153177
Whiteside8362185
Jackson813295
Boone799983
Coles7984128
Ogle765290
Grundy745786
Knox7404170
Franklin7350115
Clinton7152102
Macoupin7058107
Marion6973144
Effingham6688100
Henry668677
Jefferson6613143
Livingston601598
Stephenson594194
Woodford582492
Randolph5580101
Christian539882
Fulton530778
Monroe5279104
Morgan5126100
Logan497776
Montgomery497183
Lee481962
Bureau446691
Saline438870
Perry436575
Fayette435464
Iroquois426277
McDonough378462
Shelby353349
Jersey338853
Lawrence337634
Crawford335630
Douglas331137
Union310248
Wayne308163
Richland281957
White281733
Hancock275335
Clark268740
Cass267331
Pike266958
Edgar262649
Clay262054
Bond258225
Ford247659
Warren246266
Moultrie239933
Carroll237838
Johnson232932
Jo Daviess219229
Massac218451
Wabash218219
Mason214953
Washington213728
De Witt208530
Mercer206637
Greene206040
Piatt204514
Cumberland191126
Menard173013
Jasper162121
Marshall142521
Hamilton134922
Schuyler110610
Brown107110
Pulaski105812
Edwards104418
Stark82428
Gallatin7969
Alexander74912
Henderson71614
Scott7146
Calhoun6982
Hardin61916
Putnam5684
Pope5626
Unassigned1132433
Out of IL150

Indiana Coronavirus Cases

(Widget updates once daily at 8 p.m. ET)

Cases: 1014652

Reported Deaths: 16632
CountyCasesDeaths
Marion1362182142
Lake668141176
Allen58487809
Hamilton46619469
St. Joseph44705621
Elkhart36154514
Vanderburgh32393483
Tippecanoe28081262
Johnson25261448
Hendricks24008364
Porter23070369
Madison18875414
Clark18786255
Vigo17578305
Monroe15361199
LaPorte15279252
Delaware15163265
Howard14904294
Kosciusko12479149
Hancock11802177
Bartholomew11730181
Warrick11323188
Floyd11199217
Wayne11057255
Grant10197221
Morgan9523179
Boone8994117
Dubois8308133
Henry8287155
Dearborn825795
Noble8106108
Marshall8026136
Cass7584123
Lawrence7502172
Shelby7239117
Jackson703990
Gibson6638115
Harrison654593
Huntington6474100
Knox6444107
DeKalb6401102
Montgomery6320113
Miami598398
Putnam585980
Clinton580472
Whitley571756
Steuben571077
Jasper539483
Wabash5388105
Jefferson515497
Ripley503988
Adams487276
Daviess4704116
Scott441876
Clay429160
Greene428996
Wells426888
White422965
Decatur4184105
Fayette407588
Jennings392563
Posey378444
LaGrange364579
Washington361651
Randolph349799
Spencer341543
Fountain337660
Sullivan331652
Starke320971
Fulton318068
Owen317671
Orange296164
Jay286946
Franklin266943
Perry266252
Rush265732
Carroll263234
Vermillion260754
Parke233029
Pike230044
Tipton229859
Blackford195443
Pulaski185357
Newton160849
Crawford160526
Benton151817
Brown148247
Martin139819
Switzerland136011
Warren121616
Union107316
Ohio85313
Unassigned0550