Novartis completes certification of initial sites in Quebec for first approved Canadian CAR-T therapy, Kymriah (tisagenlecleucel)(i) – Canada NewsWire

DORVAL, QC, Oct. 9, 2019 /CNW/ - Novartis Pharmaceuticals Canada Inc. is pleased to announce that sites in Quebec have been certified in accordance with applicable requirements to treat eligible patients with Kymriah (tisagenlecleucel), the first chimeric antigen receptor T cell (CAR-T) therapy that received regulatory approval in Canada. Patients with relapsed/refractory (r/r) pediatric and young adult B-cell acute lymphoblastic leukemia (ALL) and adult r/r diffuse large B-cell lymphoma (DLBCL) may be eligible to be treated with Kymriah at one of the initially certified Canadian treatment sites. This news coincides with the Quebec government announcement that Kymriah is now reimbursed for eligible patients under the Rgie de l'assurance maladie du Qubec (RAMQ)ii.

Eligible patients in Quebec are now able to access Kymriah from the Centre hospitalier universitaire (CHU) Sainte-Justine and Maisonneuve-Rosemont Hospital (HMR) in Montreal.

"Novartis feels it is important to acknowledge the collaborative effort by all stakeholders involved to ensure Canadians have access to the first approved CAR-T therapy for patients with B-cell ALL and DLBCL who historically have poor outcomes. With treatment centers certified in Quebec, this allows patients with these two life-threatening cancers the opportunity to be treated with CAR-T therapy," said Daniel Hbert, Medical Director, Novartis Pharmaceuticals Canada Inc. "Novartis is committed to bringing additional qualified treatment centers from other parts of the country into the network to give Canadians the opportunity to be treated closer to home."

Due to the sophisticated and individualized nature of Kymriah, treatment sites that are part of the network are required to be FACT-accredited (Foundation for the Accreditation of Cellular Therapy), qualified to perform intravenous infusion of stem cells collected from the bone marrow of a donor, also referred to as allogeneic hematopoietic stem cell transplantation (alloSCT) and have experience with cell therapies, leukemia and lymphoma to facilitate safe and seamless delivery of Kymriah to eligible patients.

"We are thrilled with this news because we will now be able to treat patients at our institution with the knowledge that their therapy will be publicly funded. We see this as a significant step forward. The young patients we see who have refractory or relapsed B-cell ALL are desperately in need of a new treatment option. Kymriah brings hope to patients who are literally in a fight for their life." said Dr. Henrique Bittencourt, hematologist at the CHU Sainte-Justine in Montreal and Associate Professor, Department of Pediatrics, Universit de Montral.

"The expertise at HMR has raised the profile of our organization, which is a major Quebec, Canadian and worldwide pole for health innovation. Thanks to the dedicated work of our care, research and teaching teams, patients can now access this new treatment with demonstrated effectiveness and impact on quality of life," said Sylvain Lemieux, President and CEO, Centre intgr universitaire de sant et de services sociaux (CIUSSS) de l'Est-de-l'le-de-Montral.

About Kymriah Kymriah (tisagenlecleucel), a CD19-directed genetically modified autologous T-cell immunocellular therapy, is approved to treat two life-threatening cancers that have limited treatment options and historically poor outcomes, demonstrating the critical need for new therapies for these patients.

Kymriah is approved by Health Canada for use in pediatric and young adult patients 3 to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) who are refractory, have relapsed after allogenic stem cell transplant (SCT) or are otherwise ineligible for SCT, or have experienced second or later relapse; and for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high grade B-cell lymphoma and DLBCL arising from follicular lymphomai.

Kymriah is a one-time treatment that uses a patient's own T cells to fight and kill cancer cells. Bringing this innovative therapy to Canadian patients requires collaboration among many health system stakeholders.

Kymriah (tisagenlecleucel) Important Safety InformationThe full prescribing information for Kymriah can be found at: http://www.novartis.ca

Novartis Leadership in Cell and Gene TherapyNovartis is at the forefront of investigational immunocellular therapy and was the first pharmaceutical company to significantly invest in CAR-T research, work with pioneers in CAR-T and initiate global CAR-T trials. Kymriah, the first approved CAR-T cell therapy in Canada, is the cornerstone of this strategy. Active research programs are underway targeting other hematologic malignancies and solid tumors, and include efforts focused on next generation CAR-Ts that involve simplified manufacturing schemes and gene edited cells.

About Novartis in CanadaNovartis Pharmaceuticals Canada Inc., a leader in the healthcare field, is committed to the discovery, development and marketing of innovative products to improve the well-being of all Canadians. In 2018, the company invested $52 million in research and development in Canada. Located in Dorval, Quebec, Novartis Pharmaceuticals Canada Inc. employs approximately 1,000 people in Canada and is an affiliate of Novartis AG, which provides innovative healthcare solutions that address the evolving needs of patients and societies. For further information, please consult http://www.novartis.ca.

About NovartisNovartis is reimagining medicine to improve and extend people's lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world's top companies investing in research and development. Novartis products reach more than 750 million people globally and we are finding innovative ways to expand access to our latest treatments. About 108,000 people of more than 140 nationalities work at Novartis around the world. Find out more at http://www.novartis.com.

Kymriah is a registered trademark.

References_____________________________________________i Novartis Pharmaceuticals Canada Inc., Kymriah Product Monograph. January 7, 2019.ii Quebec Ministry of Health and Social Services press release. October 8, 2019. Available at: https://www.newswire.ca/fr/news-releases/la-therapie-car-t-cell-maintenant-disponible-au-quebec-821953237.html

SOURCE Novartis Pharmaceuticals Canada Inc.

For further information: Novartis Media Relations, Daphne Weatherby, Novartis Corporate Communications, +1 514 633 7873, E-mail: camlph.communications@novartis.com

http://www.novartis.ca

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Novartis completes certification of initial sites in Quebec for first approved Canadian CAR-T therapy, Kymriah (tisagenlecleucel)(i) - Canada NewsWire

Novo Nordisk and bluebird bio Enter 3-Year Gene Therapy Collaboration Pact – BioSpace

Cambridge, Massachusetts-based bluebird bio and Bagsvaerd, Denmark-based Novo Nordisk announced they have agreed to collaborate to develop next-generation genome editing therapies for genetic diseases, including hemophilia. The deal will last three years, with a top priority to develop a gene therapy for hemophilia A.

The partnership will leverage bluebirds mRNA-based megaTAL technology that is used to silence, editor or insert genetic components. Novo Nordisk has a hemophilia portfolio. The initial focus will be on correcting FVIII-clotting factor deficiency. No financial details were disclosed.

MegaTALs are a single-chain fusion enzyme. It combines the natural DNA cleaving processes of Homing Endonucleases (HEs) with the activity of transcription activator-like (TAL) effectors at the DNA binding region. These proteins are easily engineered to recognize specific DNA sequences.

We are pleased to announce our collaboration with bluebird whose demonstrated capabilities in gene therapy will enable the next-generation of innovative products to make a significant impact on patients lives, said Marcus Schindler, Novo Nordisks senior vice president for Global Drug Discovery.

He went on to say, This important research collaboration aimed at addressing genetic diseases at the DNA level reflects Novo Nordisks enduring commitment and dedication to inventing disease-modifying medicines that can truly change the lives of people living with hemophilia and other genetic diseases.

Novo Nordisk is better known for its strong presence in the diabetes market and for metabolic diseases. However, the company has been increasing its efforts in hemophilia, with its hemophilia A drug Esperoct receiving approval from both the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) this year.

Hemophilia A is found in about one in 5,000 people and hemophilia B in about one in 25,000 male births. It is estimated that more than 400,000 males have hemophilia A or B, which is severely underdiagnosed in developing countries. About 304,000 people are diagnosed with hemophilia A, the result of decreased or defective production of the blood clotting factor VIII. Hemophilia B is not as common, but affects about 136,000 people who have deficiencies in clotting factor IX.

Hemophilia patients often have bleeding into the joints, particularly knees and ankles, and can have uncontrolled bleeding from trauma, surgery, tooth extractions or other minor surgical treatments.

Bluebird bio is a pioneer of gene therapy. On June 3, the European Commission (EC) granted the company conditional marketing approval for its LentiGlobin gene therapy for transfusion-dependent beta-thalassemia (TDT) under the brand name Zynteglo. It was approved for patients 12 years or older with transfusion-dependent beta-thalassemia who did not have a 0/0 genotype and for patients where hematopoietic stem cell (HSC) transplantation wasnt appropriate, but a human leukocyte antigen (HLA)-matched related HSC donor isnt available.

The therapy came with a $1.8 million price tag in Europe, although it has offered a variety of pricing schemes, including a five-year payment plan with annual payments contingent on the therapys continued effectiveness, to offset criticism of the price.

Of the deal with Novo Nordisk, Philip Gregory, bluebirds chief scientific officer, stated, bluebird has made tremendous progress on enabling an in vivo gene editing platform based on our megaTAL technology, including important advances in high-quality mRNA production and purification. We believe this technology has the potential to create a highly differentiated approach to the treatment of many severe genetic diseases. Moreover, we are thrilled to be able to combine this new platform technology with Novo Nordisks deep expertise in hemophilia research and therapeutics. We believe this collaboration will move us toward our shared goal of recoding the treatment paradigm and substantially reduce the burden of disease for patients with factor VIII deficiency.

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Novo Nordisk and bluebird bio Enter 3-Year Gene Therapy Collaboration Pact - BioSpace

Preclinical Data Indicating Allocetra-OTS As Potential Therapy For Prevention Of Organ Failure And Mortality Associated with Severe Sepsis Selected…

Nes-Ziona, Israel, Oct. 10, 2019 (GLOBE NEWSWIRE) -- Enlivex Therapeutics Ltd. (Nasdaq:ENLV), a clinical-stage immunotherapy company, today announced today that the European and Int'l Shock Societies selected, for an oral presentation, Pathogen- and damage-associated molecular patterns are immune modified by apoptotic cell adjuvant therapy for acute sepsis in a cecal ligation and puncture mice model, and avoids multi-organ failure and improves survival to be presented at the XVIIIth Congress of the European Shock Society and IXth Congress of the Int'l Federation of Shock Societies, on October 11, 2019, 11:40am, held at the Avra Imperial Hotel & Conference Center, Chania, Crete, Greece.

The presentation details results of preclinical studies, which were designed to evaluate the effect of Allocetra-OTS immunotherapy on subjects with highly-severe sepsis. The data showed ten-fold (10x) increased survival for study subjects who were treated with Allocetra-OTS therapy and antibiotics and fluids, as compared to subjects treated solely with antibiotics and fluids. Specifically, the levels of cytokine storms and organ failures were dramatically lower in the Allocetra-OTS group, leading to improved survival.

Enlivex previously reported positive interim safety and tolerability of Allocetra-OTS in six patients with severe sepsis as part of an ongoing Phase Ib clinical trial. These interim safety results, taken together with the efficacy profile of improved survival and reduced cytokine storms and organ damage, present Allocetra-OTS as a potential candidate to become the first therapy ever to be approved for severe sepsis, stated Dror Mevorach, M.D., Chief Scientific and Medical Officer of Enlivex.

The XVIIIth Congress of the European Shock Society and IXth Congress of the Int'l Federation of Shock Societies is focused on hot topic key notesprovided by world-known experts. Current topics with focus on trauma/hemorrhagic shock/sepsis discussed during the conference include immune and organ responses, novel pathways, trauma modelling, comorbidities, novel therapies, long term effects, precision modeling, international shock research.

ALLOCETRATMby Enlivex was designed toprovide a novel immunotherapy mechanism of actionthat targets life-threatening clinical indications that are defined as unmet medical needs, includingprevention or treatment of complications associated with bone marrow transplantations (BMT) and/or hematopoietic stem cell transplantations (HSCT); organ dysfunction and acute multiple organ failure associated with sepsis; and enablement of an effective treatment of solid tumors via immune checkpoint rebalancing.

ABOUT ENLIVEXEnlivex is a clinical stage immunotherapy company, developing an allogeneic drug pipeline for immune system rebalancing. Immune system rebalancing is critical for the treatment of life-threatening immune and inflammatory conditions which involve an out of control immune system (e.g. Cytokine Release Syndrome) and for which there are no approved treatments (unmet medical needs), as well as solid tumors immune-checkpoint rebalancing. For more information, visit http://www.enlivex.com.

ABOUT THE EUROPEAN SHOCK SOCIETY

The primary objective of the European Shock Society is to advance understanding of the pathophysiology and to improve treatment of shock, trauma and sepsis and/or allied disciplines. For more information, visit https://www.europeanshocksociety.org/

Safe Harbor Statement: This press release contains forward-looking statements, which may be identified by words such as expects, plans, projects, will, may, anticipates, believes, should, would, intends, estimates, suggests, has the potential to and other words of similar meaning, including statements regarding expected cash balances, market opportunities for the results of current clinical studies and preclinical experiments, the effectiveness of, and market opportunities for, ALLOCETRATMprograms, which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that forward-looking statements involve risks and uncertainties that may affect Enlivexs business and prospects, including the risks that Enlivex may not succeed in generating any revenues or developing any commercial products; that the products in development may fail, may not achieve the expected results or effectiveness and/or may not generate data that would support the approval or marketing of these products for the indications being studied or for other indications; that ongoing studies may not continue to show substantial or any activity; and other risks and uncertainties that may cause results to differ materially from those set forth in the forward-looking statements. The results of clinical trials in humans may produce results that differ significantly from the results of clinical and other trials in animals. The results of early-stage trials may differ significantly from the results of more developed, later-stage trials. The development of any products using the ALLOCETRATMproduct line could also be affected by a number of other factors, including unexpected safety, efficacy or manufacturing issues, additional time requirements for data analyses and decision making, the impact of pharmaceutical industry regulation, the impact of competitive products and pricing and the impact of patents and other proprietary rights held by competitors and other third parties. In addition to the risk factors described above, investors should consider the economic, competitive, governmental, technological and other factors discussed in Enlivexs filings with the Securities and Exchange Commission, including under the heading Risk Factors contained in Enlivexs most recently filed Annual Report on Form 20-F. The forward-looking statements contained in this press release speak only as of the date the statements were made, and we do not undertake any obligation to update forward-looking statements, except as required under applicable law.

ENLIVEX CONTACT:Shachar Shlosberger, CFOEnlivex Therapeutics, Ltd.shachar@enlivex-pharm.com

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Preclinical Data Indicating Allocetra-OTS As Potential Therapy For Prevention Of Organ Failure And Mortality Associated with Severe Sepsis Selected...

Caroline Wyatt: The fight to reverse damage caused by MS – BBC News

Image caption Caroline Wyatt visited Prof Robin Franklin to find out more about a drug that might help stop the progression of MS

"I don't like to think of the future. It's such a big question mark. I just keep living in the present."

Karine Mather was diagnosed with MS when she was 27, although she noticed the first symptoms much earlier.

It started off as a mental-health issue with anxiety and depression, she remembers. Later, she noticed she was starting to limp when she walked longer distances.

Karine began using a walker to help with her balance and stamina, and then a scooter when she could no longer walk very far.

"I got to the stage where the wheelchair became quite liberating, and gave me back a sense of freedom again. Now I rely on the power-chair full-time because I can't stand by myself any more."

Now Karine and her wife, Sarah, have had to give up their full-time jobs.

Karine was forced to stop working as a customer service adviser at a bank because she could no longer fulfil the physical demands of work and Sarah gave up working as a data analyst so she could take care of Karine.

Now 34, Karine retains the use of just one hand, and suffers pain, stiffness and spasticity in her body that has got worse as the disease has progressed.

"It feels like a fist clenching all the time. And I have days when my mind is cloudy and I miss out words and sentences."

Both remain upbeat but the financial, as well as the emotional, impact of MS has been huge.

Karine's MS is the type known as "primary progressive", or PPMS, which meant that for the first years after diagnosis, no disease-modifying treatment was available.

One new drug - Ocrevus, or ocrelizumab - was recently licensed for early PPMS in the UK but came too late to help Karine.

Now the MS Society is launching an ambitious "Stop MS" appeal, aiming to raise 100m to fund research over the next decade into treatments that can stop the progression of disability in MS.

Since being diagnosed with MS in 2015, after many years of symptoms, I've been looking for anything that might help slow or even stop the progression of my MS, which affects the nerves in my brain and spinal cord.

I last wrote about my MS after travelling to Mexico for an autologous stem cell transplant (aHSCT) in 2017.

Sadly, despite initial improvements, I'm now back to where I was before: slowly but surely getting worse.

The only improvements that have endured are the lifting of some of the crushing brain fog I had before HSCT and less hesitation in my speech.

For both, I am eternally grateful, as they mean I can continue to work at the BBC, in the job I love.

However, I have no idea how long this reprieve will last.

The fatigue that had long been my worst symptom is now back with a vengeance, so that staying awake throughout a busy working day remains a challenge.

That MS fatigue did lift for a few months, and it felt miraculous. I awoke every day refreshed. But then it returned, and I awake after eight full hours fast asleep feeling as if I haven't been to bed at all.

The ageing process - including menopause - has almost certainly been a factor in the worsening of some symptoms.

Ageing cells repair less well, and with my faulty immune system apparently determined to keep stripping away the myelin sheath that should protect my nerves, I'm less able now to repair the damage than I was when the disease first began to affect me in around 1992.

Since 2016, I've had to walk using a stick to aid my balance. It is sparkly-topped; an effort to make the accoutrements of disability just a little more cheery.

Dizziness is now a constant companion. It rarely goes away, making car travel or even buses a nightmare. Just turning my head too fast can make me stagger or fall over.

And for the past year or two, my right foot has begun to drag along the ground thanks to foot drop, meaning that I trip more often because I can't fully raise it.

I am always grateful to the strangers who kindly stop to help me up from the uneven pavement when I do fall.

Perhaps most worrying for me is that my right hand no longer works as it used to, catching on the computer keyboard as my outer fingers drag lazily along the keys, sullenly refusing my brain's command to lift.

In the mornings, both my hands and my feet are numb and frozen, then painfully full of pins and needles before warming up enough to be usable a few hours later.

When I wake, I wonder how long it might be until these hands and feet barely function at all, and quickly push that unwelcome thought away.

I'm well aware how very lucky I am that the progression of my MS has been relatively slow - at least until recently. I've learned how better to conserve energy for the things that really matter, though I still chafe at how little I manage to achieve.

Having enough energy to cook a meal from scratch on a day off is a cause for rejoicing. I'm still learning how to save up enough energy for family and friends, and not use up all of my much-depleted ration for work or research.

I have had to face the fact that I have now probably gone from the relapsing-remitting phase of MS (for which a dozen or so treatments exist) into the secondary progressive phase, for which there is currently no treatment licensed in the UK to stop the relentless progression that will affect so many of the 100,000 or more of us living with MS here.

But that may be about to change.

Anna Williams, professor of regenerative neurology at the University of Edinburgh, is looking at how the brain responds to MS damage and how the fatty myelin sheath under attack in MS can be restored more efficiently.

"We have to look at ways to stop the nerves dying," she says. "We want to be able to try to limit that either by keeping the nerves alive, or keeping them working better."

Repurposing existing drugs to help with remyelination should prove the quickest route to therapies for progressive forms of MS, because creating and licensing new ones is a much lengthier and more expensive process.

Prof Williams still sees patients at the Anne Rowling Clinic of Regenerative Neurology in Edinburgh, named in memory of the Harry Potter author J K Rowling's mother, who had MS. (The author this year donated 15m for research at the unit.)

"At the moment, with PPMS or SPMS, we can always give relief for pain or stiffness but we won't change the course of the disease.

"So for those patients, to slow or stop or reverse the disease can only be done with more research, and money is critical for research."

The biggest trial yet in the UK for patients with secondary progressive MS is the MS STAT2 trial, conducted by Prof Jeremy Chataway for the UCL Queen Square Institute of Neurology in London.

The trial is still recruiting at 30 centres across the UK to look at whether simvastatin, a drug used to treat high cholesterol, can slow or stop disability progression. If so, it has the potential to become one of the first disease-modifying therapies for people with secondary progressive MS.

And perhaps most encouraging of all, Prof Robin Franklin and his team at the Wellcome-MRC Cambridge Stem Cell Institute recently published research suggesting a common diabetes drug - metformin - could hold the key to stopping disease progression in MS.

Costing just a few pence per tablet, metformin appears to have an ability to restore cells to a younger, healthier state and encourage myelin regrowth.

The next question is whether it works in people as well as it does in the lab.

Prof Franklin says: "This is a drug that's well tolerated and widely available. There is every reason to believe that the effects that we have seen - which have been so spectacular - will translate into humans.

"This is the great frontier of MS therapy. We're good at stopping the inflammation in MS. What we're not so good at doing is repairing the damage. All this work has given us some real hope that this medicine will reverse the damage done by MS."

I certainly feel rather more hopeful than I did.

I've changed as much about my lifestyle as I can - prioritising sleep, eating healthily, largely giving up alcohol, doing yoga and stretching every day, and cutting back on stress, be that reporting from war zones or attending too many BBC meetings.

But I'm all too aware that time is against me as my ageing brain and body struggle to repair the damage done in their lengthy continuing battle with my own immune system.

My hope now is that these trials will show good enough results in the next few years for at least one or two of the drugs to be rapidly approved for MS so they can help people like Karine and me before it's too late.

I ask Karine what she makes of the current research.

She is suitably succinct.

"I'm sitting here with just the one limb working and I'm thinking - quicker, please."

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Caroline Wyatt: The fight to reverse damage caused by MS - BBC News

AVROBIO Announces First Patient Dosed in Phase 1/2 Trial of Gene Therapy for Cystinosis – Business Wire

CAMBRIDGE, Mass.--(BUSINESS WIRE)--AVROBIO, Inc. (NASDAQ: AVRO) (the Company) today announced that the first patient has been dosed in the Companys AVR-RD-04 investigational gene therapy program for cystinosis, a devastating lysosomal storage disease, in an ongoing Phase 1/2 clinical trial sponsored by academic collaborators at the University of California San Diego. The gene therapy is derived from the patients own hematopoietic stem cells, which are genetically modified to produce functional cystinosin, a crucial protein that patients with cystinosis lack.

The trial will enroll up to six patients with cystinosis, a rare inherited disease caused by a defect in the gene that encodes for cystinosin. The cystinosin protein enables transport of the amino acid cystine out of lysosomes. When it is absent, cystine accumulates and crystalizes, causing progressive damage to the kidneys, liver, muscles, eyes and other organs and tissues. Cystinosis affects both children and adults; they face shortened life spans and often painful symptoms, including muscle wasting, difficulty breathing, blindness and kidney failure.

Cystinosis is a debilitating and progressive disease, and new treatment options are sorely needed. The current standard of care does not avert deterioration; at best, it can attenuate symptoms. Thats why gene therapy is particularly exciting: It has the potential to change the course of disease -- and the lives of patients -- by addressing the underlying cause of cystinosis, said Birgitte Volck, MD, PhD, President of Research and Development at AVROBIO. We believe we can engineer patients own stem cells so they sustainably produce the functional protein that is needed to prevent a toxic buildup of cystine and halt progression of the disease. We are so pleased that this investigational gene therapy is now in the clinic in collaboration with Dr. Stephanie Cherqui at UC San Diego.

The single-arm trial will enroll four adults and a potential follow-on cohort of two adults or adolescents at least 14 years of age who are currently being treated with cysteamine, the standard of care for cystinosis. If started at an early age and taken on a strict dosing schedule, cysteamine can delay kidney failure. However, the treatment regimen is highly burdensome, with side effects that can be severe and unpleasant, and many patients find it difficult to adhere to this treatment regimen. Even if compliance is high, cysteamine therapy cannot prevent kidney failure or avert other complications.

For people with cystinosis, there are no healthy days. They must take dozens of pills a day, around the clock, just to stay alive. It is a relentless disease and we urgently need new treatments, said Nancy J. Stack, President of the Cystinosis Research Foundation, which supported development of the gene therapy with more than $5.4 million in grants to Dr. Cherquis lab at UC San Diego. We believe that we are now an important step closer to the potential cure that our community has been working toward for many years.

The trials primary endpoints are safety and tolerability, assessed for up to two years after treatment, as well as efficacy, as assessed by cystine levels in white blood cells. Secondary endpoints to assess efficacy include changes in cystine levels in the blood, intestinal mucosa and skin and cystine crystal counts in the eye and skin. Efficacy will also be evaluated through clinical tests of kidney function, vision, muscle strength, pulmonary function and neurological and psychometric function, as well as through assessments of participants quality of life after treatment. The trial is funded by grants to UC San Diego from the California Institute for Regenerative Medicine (CIRM) as well as the Cystinosis Research Foundation.

This investigational gene therapy starts with the patients own stem cells, which are genetically modified so that their daughter cells can produce and deliver functional cystinosin to cells throughout the body. With this approach we aim to prevent the abnormal accumulation of cystine that causes so many devastating complications, said Stephanie Cherqui, PhD, an Associate Professor of Pediatrics at UC San Diego School of Medicine, and consultant to AVROBIO. We have been working toward this trial for years and we are grateful for all the support that brought us to this moment.

About AVR-RD-04

AVR-RD-04 is a lentiviral-based gene therapy designed to potentially halt the progression of cystinosis with a single dose of the patients own hematopoietic stem cells. The stem cells are genetically modified so they can produce functional cystinosin with the aim of substantially reducing levels of cystine in cells throughout the patients body. Before the infusion of the cells, patients undergo personalized conditioning with busulfan to enable the cells to permanently engraft. The Phase 1/2 clinical trial is being conducted under the name CTNS-RD-04 by AVROBIOs academic collaborators at the University of California, San Diego.

About Cystinosis

Cystinosis is a rare, inherited lysosomal storage disorder characterized by the accumulation of cystine in all the cells of the body, resulting in serious and potentially fatal damage to multiple organs and tissues and the shortening of patients life spans. The kidneys and eyes are especially vulnerable; more than 90% of untreated patients require a kidney transplant before age 20. An estimated 1 in 170,000 people are diagnosed with cystinosis.

About AVROBIO, Inc.

AVROBIO, Inc. is a leading, Phase 2 gene therapy company focused on the development of its investigational gene therapy, AVR-RD-01, in Fabry disease, as well as additional gene therapy programs in other lysosomal storage disorders including Gaucher disease, cystinosis and Pompe disease. The Companys plato platform includes a proprietary vector system, automated cell manufacturing solution and a personalized conditioning regimen deploying state-of-the-art precision dosing. AVROBIO is headquartered in Cambridge, MA and has offices in Toronto, ON. For additional information, visit http://www.avrobio.com.

Forward-Looking Statements

This press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as aims, anticipates, believes, could, estimates, expects, forecasts, goal, intends, may, plans, possible, potential, seeks, will and variations of these words or similar expressions that are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements regarding the therapeutic potential of our product candidates, the design, commencement, enrollment and timing of ongoing or planned clinical trials, including the ongoing Phase 1/2 trial of the Companys AVR-RD-04 investigational gene therapy, the anticipated benefits of our gene therapy platform, the expected safety profile of our product candidates, timing and likelihood of success of our current or future product candidates, and the market opportunity for our product candidates. Any such statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Results in preclinical or early stage clinical trials may not be indicative of results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements, or the scientific data presented.

Any forward-looking statements in this press release are based on AVROBIOs current expectations, estimates and projections about our industry as well as managements current beliefs and expectations of future events only as of today and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that any one or more of AVROBIOs product candidates will not be successfully developed or commercialized, the risk of cessation or delay of any ongoing or planned clinical trials of AVROBIO or our collaborators, the risk that AVROBIO may not realize the intended benefits of our gene therapy platform, including the features of our plato platform, the risk that our product candidates or procedures in connection with the administration thereof will not have the safety or efficacy profile that we anticipate, the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical or clinical trials, will not be replicated or will not continue in ongoing or future studies or trials involving AVROBIOs product candidates, the risk that we will be unable to obtain and maintain regulatory approval for our product candidates, the risk that the size and growth potential of the market for our product candidates will not materialize as expected, risks associated with our dependence on third-party suppliers and manufacturers, risks regarding the accuracy of our estimates of expenses and future revenue, risks relating to our capital requirements and needs for additional financing, and risks relating to our ability to obtain and maintain intellectual property protection for our product candidates. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause AVROBIOs actual results to differ materially and adversely from those contained in the forward-looking statements, see the section entitled Risk Factors in AVROBIOs most recent Quarterly Report on Form 10-Q, as well as discussions of potential risks, uncertainties and other important factors in AVROBIOs subsequent filings with the Securities and Exchange Commission. AVROBIO explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.

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AVROBIO Announces First Patient Dosed in Phase 1/2 Trial of Gene Therapy for Cystinosis - Business Wire

We believe we can stop MS, and this is how – Metro.co.uk

Weve reached a point where we know whats causing the disease to progress (Picture: MS Society)

Twenty-five years ago there were no treatments for multiple sclerosis (MS) a neurological condition that affects more than 100,000 people living in the UK.

Today the picture is very different. There have been major advances in treatment and, following a series of more recent discoveries, we believe we can stop MS.

Weve reached a point where we know whats causing the disease to progress.

In people with MS, a protective substance that surrounds your nerves called myelin becomes damaged, which makes it harder for messages to get received, causing problems with how a person walks, moves, eats and thinks. Without this protective coating nerve cells become vulnerable, and once a nerve cell is lost, this causes disability.

Finding treatments that can regenerate myelin has eluded scientists for decades it has been the major missing piece of the MS treatment puzzle.

The UK is a world leader in this kind of research and we now know that it is possible to repair it. We have teams of researchers focused on understanding why the repair process breaks down and finding ways to kick-start it again.

Just last week, new research in Cell Stem Cell revealed a new route through which we may be able to enhance myelin repair with a common diabetes drug. Years of hard work and research from dedicated scientists have gone in to making this possible, and this outcome shows what a significant time were living in.

Finding treatments that protect nerves is the second missing piece of our jigsaw and clinical trials of potential treatments are already underway.

Finding these new treatments to protect nerves and repair the coating that surrounds them will help us slow or stop MS progressing, and will mean people dont have to worry about one day relying on a wheelchair, or losing their independence.

Researchers are using their increasing knowledge of nerves to design new ways to keep them alive and healthy. These include clearing up debris left over from myelin attacks, energising nerves, and improving transport of important molecules in the nerves.

Although research has brought us to a critical point, and we believe we can stop MS, funding research and clinical trials is very expensive and theres lots more work to do before we get to where we need to be.

I have the privilege of leading the Scientific Steering Committee of the International Progressive MS Alliance, which brings together MS charities, scientists and people affected by MS to drive forward research like the above, and ultimately accelerate the development of new treatments in progressive MS.

Ive also been personally involved in exploring the mechanisms underpinning progression, using imaging to determine what happens to people with progressive MS.

The shape of treatment has changed dramatically over my career. However, there are still so many people with MS who dont have any treatment because those that do exist only work on damage caused by the immune system. They dont stop the slow burn of MS progression, which ultimately causes disability.

Finding these new treatments to protect nerves and repair the coating that surrounds them will help us slow or stop MS progressing, and will mean people dont have to worry about one day relying on a wheelchair, or losing their independence. I can now say confidently that the future will look very different for people living with this condition.

For the first time, the international research community is aligned on what needs to be done and, with a dramatic increase in investment, we could genuinely change peoples lives.

Thats what were working on now, and its never been a more exciting time.

The MS Societys Stop MS Appeal needs to raise 100 million to find treatments for everyone living with MS. To donate to the Stop MS Appeal or for more information visit mssociety.org.uk/stop. Or text FUTURE6 to 70800 to donate 5.

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We believe we can stop MS, and this is how - Metro.co.uk

World Cord Blood Day 2019 to Welcome Leading Transplant Doctors and Pioneering Cellular Therapy Researchers – PRNewswire

TUCSON, Ariz., Oct. 9, 2019 /PRNewswire/ -- World Cord Blood Day (November 15th, 2019) is a free event and open to the public. In addition to events worldwide, World Cord Blood Day will feature a free online conference. Renowned researchers and leading transplant doctors will give introductory presentations for the public as well as academic lectures specifically designed for healthcare professionals.

Attendees will learn about the 40,000+ cord blood transplants performed since 1988 to treat over 80 life-threatening diseases including sickle cell anemia, thalassemia, lymphoma and leukemia. In addition, attendees will learn about exciting advances in the emerging field of regenerative medicine to potentially treat autism, cerebral palsy, spinal cord injury and more.

As the host and organizer of World Cord Blood Day 2019, Save the Cord Foundation is proud to announce the following speakers for this year's program (in order of appearance): Dr. Joanne Kurtzberg (Duke Department of Pediatrics, Duke Center for Autism and Brain Development), Dr. Karen Ballen (University of Virginia), Dave Murphy and Monroe Burgess (Quick Specialized Healthcare Logistics), Dr. Wise Young (Rutgers University), Dr. Elizabeth Shpall (MD Anderson Cancer Center), Dr. Filippo Milano (Fred Hutchinson Cancer Research Center). In addition, attendees will hear from Dr. Alexes Harris who beat cancer thanks to a cord blood transplant from a donor and young Luke Fryer who was treated for cerebral palsy with his own cord blood in a clinical trial.

The morning session will focus on the success of cord blood transplants over the past 30 years and how transplant doctors use cord blood stem cells today, namely, to fight blood cancer. The afternoon session will look at new directions in cord blood research. Attendees will receive updates on several ground-breaking clinical trials using cord blood in regenerative medicine, cellular therapy and more. To view the full agenda, please visit: https://www.worldcordbloodday.org/online-medical-conference-agenda.html

Organized and hosted by Save the Cord Foundation (501c3 non-profit), this year's event is officially sponsored by Quick Specialized Healthcare Logistics. Inspiring Partners include the Cord Blood Association (CBA), Be the Match (NMDP), World Marrow Donor Association (WMDA-Netcord), AABB Center for Cellular Therapy and Foundation for the Accreditation of Cellular Therapy (FACT).

Visit http://www.WorldCordBloodDay.org to learn how you can participate and/or host an event. Join us on social media using the hashtags: #WCBD19 and #WorldCordBloodDay.

About Save the Cord Foundation

Save the Cord Foundation (a 501c3 non-profit) was established to advance cord blood education. The Foundation provides non-commercial information to parents, health professionals and the public regarding methods for saving cord blood, as well as current applications using cord blood and the latest research. Learn more at http://www.SaveTheCordFoundation.org.

About Quick Specialized Healthcare Logistics

Quick is the trusted logistics leader serving the Healthcare and Life Science community for almost 40 years. Quick safely transports human organs and tissue for transplant or research, blood, blood products, cord blood, bone marrow, medical devices and personalized medicine, 24/7/365. Quick's specially trained experts work with hospitals, laboratories, blood banks and medical processing canters, and utilize the safest routes to ensure integrity, temperature control and chain of custody throughout the transportation process. Learn more at http://www.quickhealthcare.aero.

Media contact:Charis Ober225955@email4pr.com520-419-0269

SOURCE Save the Cord Foundation - World Cord Blood Day

http://www.savethecordfoundation.org/

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World Cord Blood Day 2019 to Welcome Leading Transplant Doctors and Pioneering Cellular Therapy Researchers - PRNewswire

Eurecon Verlag GmbH: 20th Pharma Trend Image & Innovation Awards The Winners and Runner-ups – BioSpace

Oct. 10, 2019 10:03 UTC

BOCAhealth with its body fluids manager receives the Pharma Trend 2019 Most Innovative Product award in the startups category. Runner-up is Surge-on Medical with its freedimensional surgical instruments. The third places goes to AiCuris Letermovir, a drug for the prophylactic anti-cytomegalovirus therapy for those who have undergone bone marrow transplantation.

MUNICH--(BUSINESS WIRE)-- An interdisciplinary jury of ten evaluated the applications by medical startups in the categories biotechnology, medical technology and digital health. The products and projects ranked among the top 3 received the Most Innovative Product Award. The discipline-specific awards were presented during the Pharma Trend Image & Innovation Awards, which took place on September 17, 2019, at the German Museum in Munich, this year marking the 20th award ceremony.

The jury assessed the submitted product and project applications based on criteria such as the benefit for the patients, the innovative content, efficiency in application and the transition to standard care. In 2019, the following companies received the Most Innovative Product award:

Digital health: BOCAhealth, the body fluids manager of the future

Body fluids disorders (dehydration or its opposite, chronic fluid retention) are a common and risky issue in many clinical situations, especially in heart failure, chronic kidney disease and elderly patients. It is estimated that every other patient is released from hospital with a hydration problem, and their 1-year mortality is up to 30%. Inside the hospital ward, the patients hydration status is checked through the inaccurate fluid balance (inflow of infusions outflow of urine). At home the patients use weight scales that do not allow an accurate assessment of body water changes either. So far, there is no accurate, easy to use, digital and versatile solution for both hospital and home monitoring.

BOCAhealth is a portable bioimpedance device connected with a smartphone application that easily measures the patients hydration and nutrition status and estimates their cardiac output and systemic vascular resistance. The BOCAhealth software provides doctors with a real-time risk prediction score based on artificial intelligence to guide the infusion and medical therapy.

BOCAhealth is the first body fluid composition analyzer that combines portability, accuracy and a risk predictor score based on artificial intelligence. These benefits convinced the jury to grant BOCAhealth the award for the Most Innovative Product. The award was accepted by the CEO and founder Dr. Allesandro Faragli.

Medical technology: Surge-on Medical, Freedimensional surgical instruments to empower surgeons

Founded in 2015 in the Netherlands, Surge-on Medical has developed the next generation of minimally invasive surgical instruments. Through cable-free technologies, they have created freedimensional instruments that provide better access to surgical areas and replace current pre-bent instrumentation, while complying with current and future FDA and European regulation. Surge-on Medical has been granted four international patents which make minimally invasive instruments steerable, detachable and cleanable. The company is currently active in arthroscopy, laparoscopy and robotic surgery, but it is also preparing to expand to additional surgical fields to keep empowering surgeons. It aims to become the worldwide leader in the development of minimally invasive instruments.

The Most Innovative Product award for the second place was accepted by Dr. Tim Horeman, CTO of Surge-on Medical.

Biotechnology: Letermovir (Prevymis) by AiCuris

AiCuris has developed a new agent against the human cytomegalovirus (HCMV), which occurs around the world. More than half of the global population are chronically infected with the virus, but only patients with a weakened or lacking immune system are at risk of serious illness or even death. The new agent Letermovir inhibits an enzyme within the virus and thus prevents its spread without damaging the host cell. This allows very good tolerability, which for the first time enables prophylactic life-saving therapy.

Letermovir was initially developed, and has already been successfully applied, for HCMV prophylaxis in patients who have undergone stem cell and bone marrow transplantation. Following a successful phase 3, Letermovir was approved in the USA, Canada, Japan and other countries as part of a process of introducing the drug to the global market. In the future, Letermovir will also benefit organ transplant recipients, AIDS patients and new-borns. The drug has been available from German pharmacies since 2018 under the brand MSD brand name Prevymis. It was very well received by the medical community and significantly exceeds revenue expectations in the first months of sales.

AiCuris was founded in 2006 as a spin-off from what was then Bayer research division on infectious diseases. Since then, the company has been researching and developing new drugs to treat virological and bacteriological conditions. In 2012, AiCuris was able to conclude a much-noticed license agreement with MSD concerning HCMV drugs.

Dr. Holger Zimmermann, CEO of AICuris, accepted the third-place award The Most Innovative Product on behalf of his company.

A successful jubilee ceremony

The patron to the jubilee awards ceremony was the Bavarian Permanent Secretary for Health, Melanie Huml. Around 140 invited decision-makers from the pharmaceuticals industry and health care communications agencies attended the event. Keynote speakers were Dr. Peter-Andreas Lschmann, board member of Bio Deutschland (the German biotechnology industry association), and Dr. Thomas Rodenhausen, board member of Harris Interactive AG. The host for the night was Tamara Sedmak, who regularly presents on TV channels including Sat 1, n-tv and N24.

For more information on Pharma Trend, see https://pharma-trend.com/en/pharma-award/ https://youtu.be/ZTnvSoPeZfQ

View source version on businesswire.com: https://www.businesswire.com/news/home/20191010005379/en/

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Eurecon Verlag GmbH: 20th Pharma Trend Image & Innovation Awards The Winners and Runner-ups - BioSpace

Sarah Ferguson admits shes had Botox, TWO types of facelift and vitamin injections in a bid to stay youthful – The Sun

LESS than a week away from her 60th birthday, Sarah Ferguson has revealed that she has had Botox, two types of facelift and organic fillers to wind back the clock.

Many royal fans marvelled when the Duchess of York stepped out looking surprisingly youthful for her daughter Princess Eugenies high profile royal wedding last year.

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Addressing rumours of cosmetic surgery, Fergie has confessed that her looks arent entirely natural and she has had professional tweaks.

Speaking to the Mail, she said: The happiness was shining out of me because my daughter was getting married. I was so glad. I love Jack. When Im passionate about anything, my eyes shine.

Above all, it was being joyful for Eugenie that made me look good. But Id had some laser treatment on my face which helped, too.

Although she previously had Botox to tackle facial lines, Sarah admitted she now prefers having laser cosmetic procedures, which are pain-free, non-invasive and take just 90 minutes.

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Mum-of-two Sarah goes to Harley Streets Dr Gabriela Mercik, who is the creator of the worlds first 6-Dimension Ultimate Laser Treatment facelift, which Fergie has now tried.

Sarah first met Dr Gabriela in 1992 when the royal was visiting young cancer victims in Upper Silesia, Poland.

At the time, Dr Gabriela was a medical student helping to treat the patients, and she ended up staying in touch with loyal Sarah.

Fergie first became one of her customers after Gabriele opened her own aesthetic clinic in the UK, and the royal felt her fair skin was too exposed to sunshine as a child.

Sarah said: I live on jingly-jangly nerves. Im very focused, earnestly intense, but I live at high speed. I dont sit down for long. Im always saying to Dr Gabriela, Come on, come on! Hurry up! Im the worst patient.

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She opts for the rejuvenating ultimate facelift, which can be done in a lunch hour and involves boosting the skins production of collagen.

Fergie admitted she had Botox a long time ago when alternative treatments werent on the market, but she now prefers having the facelifts.

The royal said shes not a fan of the frozen look as she is so animated, and also hates needles.

Despite her fears of the surgical tool, she opted for a mesotherapy beauty treatment at the clinic in 2013, which is when vitamins, minerals and amino acids are injected under the faces mesodermal layer to plump skin.

Now she has moved on to organic fillers, which are non-invasive injectable used to tackle lines and wrinkles.

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Five years ago, Dr Gabriela suggested Sarah had a thread lift also known as a puppet lift which is when threads are inserted in to the skin to make a mesh which pulls the face upwards.

Although results last for two years, the threads dissolve over six to eight months.

Sarah said: Before I had it done I thought, Oh this is going to be painful, but it wasnt bad. My skin responded well. I think if you look at photos of me after I had it done, I look much better.

She now hopes the 3,750 6-Dimension Ultimate Laser Treatment facelift will help her look her best for her 60th birthday milestone next Tuesday.

The doctor confirmed that Sarah does pay for treatments at her discretion as the pair have become close friends.

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Sarah admitted that the drive to have facial cosmetic surgery comes from skin damage that started from a young age, when her mum incorrectly thought Nivea moisturiser could be used as sunscreen.

The royal was also motivated to take care of her skin after her dad, Major Ronald Ferguson, passed away from skin cancer in 2003, and her best friend Carolyn Cotterell also died of a malignant melanoma when she was 43.

She now admits any tan she has is from a bottle and she hopes to rebuild her collagen by her birthday.

My skin responded well. I think if you look at photos of me after I had it done, I look much better.

In March she revealed she flew to the Bahamas to have a regenerative stem cell therapy on her feet, after feeling her toes were ruined by frequent horse riding when she was young.

Doctors shaved a spot near her big toe and implanted 20 million stem cells from her midriff into the cavity to make new cartilage.

Due to the surgery not yet being proven to be safe, the UK does not widely offer the treatment.

She may be turning 60, but Fergie insisted in July this year, at the launch of a British Heart Foundation campaign, that she feels sexy, sassy and super saucy.

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The proud mum has recently shared how excited she is for her eldest daughter, Princess Beatrice, to get married next year.

Taking to Instagram last month, Fergie shared six photos of the 31-year-old princess with her millionaire husband-to-be Edoardo Mapelli Mozzi.

She later shared a tweet, writing: "I know what a mother feels so I have tears of joy. I am so proud of this sensational news.

Andrew and I are just the luckiest people ever to have two great sons in law."

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Sarah recently confirmed that the "only place" Beatrice can get married is Britain.

Meanwhile its been claimed Beatrice is ready to start a family with multi-millionaire property tycoon Edoardo.

And Fergie recently honoured the family of a teen who died from severe allergy reaction after eating Pret a Manger sandwich.

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Sarah Ferguson admits shes had Botox, TWO types of facelift and vitamin injections in a bid to stay youthful - The Sun

A Doctor Plumbs The Depths Of Ivan Doig’s Illness And Asks: ‘Did He Have An Epiphany?’ – Mountain Journal

I grew up in Ohio and met my first real Westerner at age 27. Kate was from Durango, Colorado and lived next door to me for two months during a rural primary care rotation in medical school. They rolled up the sidewalks at night in Twin Falls, Idaho and so we had plenty of time to talk. Books always figured prominently in the conversation and she recommended her favorite book about the West

Reading that first iconic chapter, Time Spent, led to a 25-year Doig odyssey that eventually landed me in a Montana State University archive reading the final draft of that same chapter, marked up with Ivans own red pen.

It begins, That start of memorys gather: June 27, 1945. I have become 6 years old, my mothers life has drained out at 31 years. And in the first grey daylight, dully heading our horses around from that cabin of the past, my father and I rein away toward all that would come next.

The Doig archive at Montana State is a treasure trove for fans. Its extensively indexed and entirely on line and filled with pictures, original manuscripts and the collection of 3 x 5 and 5 x 8 cards on which Doig kept quotes and observations from his extensive research travels in Montana.

Ivan kept box after box of these cards, many of them with only a single type written sentence, sometimes annotated in longhand. He shuffled and reshuffled these bits of memory assembling them into temporary collections as material to flesh out a particular character or story line and then returned them to their boxes only to be reshuffled and reassembled for the next novel.

In summer 2019, Carol Doig met with a group of visitors and discussed her husband's journey in his last years. Joining them was her close friend, Betty Mayfield, who helped assemble Doig's edited manuscripts, diaries, correspondence and other documents that today are part of the MSU Doig collection. Those joining Carol in her living are, left to right, Betty Mayfield, Dr. Rob Patrick, Justin Shanks a post-doctoral fellow working on the Doig material to make it digitally accessible, and writer Todd Wilkinson of Mountain Journal. Photo by Kenning Arlitsch, dean of MSU Libraries

Sometimes this shuffling was frozen into a more permanent form when he collected them into 2-to-3 page novellas with titles like Scotchisms and Curses.Most assumptions arent conscious until they are shattered. Without realizing it, I had cast my favorite writer in his own movie that ran only in my head.

He woke up in the morning, hunted big game, slept with the world's most beautiful women, cavorted at the Algonquin round table, drank his weight in scotch and then, late at night, great work flowed forth from his pen in a tortured and inspired torrent. He threw himself down exhausted, only to arise and repeat the performance with the dawn. The truth that emerged from touching the physical remnants of his process was far different.

Ivan Doig was . . . a nerd . . .just like me. I clipped articles and collected them in folders, wrote down random thoughts and observations on cards, restacked, hoarded and recombined information. My stories were just about thrombocytopenia and clonal proliferation instead of resilient ranchers scraping out an existence under the Big Sky.

The champion of the lariat proletariat was a closet geek. How disappointing.But my biggest disappointment was yet to come.The archive contained an odd and alluring folder title medical journey that was irresistible to me as a physician. I hadnt realized that Ivan suffered from multiple myeloma for the last eight years of his life and had written four books after being diagnosed with a terminal disease.

Myeloma is a strange form of cancer as cancers go, it is both painstakingly slow to progress and inexorably fatal. Patients rack up complications from the treatment, not because treatment is so toxic, but because they live long enough to suffer from the cure as well as the disease.

The core of the pathology is something called a plasma cell which under normal circumstances produces the antibodies that help fight off invading viruses and bacteria. In myeloma, a single plasma cell mutates and grows uncontrollably crowding out everything else in a patients bone marrow and gumming up their organs with immunoglobulin. The mutant cells eventually cant be contained inside the bone marrow and invade the surrounding solid bone causing painful fractures in the spine and long bones of the skeleton.

As if that was not bad enough, the core of chemotherapy is high dose steroids, usually dexamethasone or prednisone. Steroids are the poster child for double edged swords in medicine. They are simultaneously incredibly useful for suppressing the immune system in autoimmune diseases, cancer and anything that involves inflammation, while at the same time having the most broad ranging side effect profile of almost any medication.

It was a love for wildlands in the West that led Rob Patrick, at right, down the trail of Ivan Doig's books and when he had an opportunity to dive deeper into Doig's final years he jumped at the chance. Another thing that brought him to Bozeman and Greater Yellowstone is his close friendship with Kenning Arlitsch, Dean of MSU Libraries. Here they are on an autumn trip into the Yellowstone backcountry.

Probably the most serious side effects for myeloma patients are immunosuppression leading to increased risk for infection, a softening of the bones accelerating the tendency of the disease to cause fractures and emotional lability. The last of these sounds trivial, but isnt.

My first patient who suffered from this particular side effect literally started a sentence laughing and ended it crying. The cognitive effects can be especially debilitating, because at its peak, the drug lulls one into a false sense of security. It can make patients feel super human and I had one multiple sclerosis patient tell me it was the most powerful antidepressant she had ever taken and she almost looked forward to her next flare so she could get it again. However, on the way up and the way down it can cause confusion and a loss of emotional control that is profoundly disturbing, especially to someone who depends on their brain to make a living. Truly a blessing and a curse of modern medicine.

One of my biggest losses of innocence after medical school was realizing that professors had pulled the wool over my eyes concerning one of the fundamental diagnostic tools in medicinethe patient history. During the pre-clinical years you seldom get to talk to an actual patient and instead hone your skills using case presentations which I later came to understand were carefully curated stories masquerading as actual patients in which the non-salient details were conveniently expunged and the salient ones amplified for teaching purposes.

My teachers smugly told me, If you dont know whats wrong by the time you finish taking the history, take the history again." This illusion is perpetuated during third year clerkships when cases are cherry picked for medical students so as not to dispel the myth. The gloves come off during internship when it is too late to turn back and you realize that most patients have a hard time telling you how they feel no matter how many creative ways you come up with to ask the same question. Its not their fault, they usually just have never felt like this before and dont have the words to describe it.

When you add intoxication, mental illness, dementia, etc. to the mix, taking a history often becomes an exercise in communication breakdown and frustration. So imagine my joy at finding a history written by a professional communicator whose livelihood depended on his ability to observe the world and record it. It was like winning the internal medicine lottery.

Doig observed of myeloma: The waiting room of hell, furnished with side effects.

Of those side effects, he observed, The dex makes me longitudinal - - concentrated on a single line of endeavor at a time, no latitude to speak of and I would go to blow my nose and find there was not a handkerchief within 50 of me. Pill bottle caps leapt for the floor. My ordinary thought process resembles a homesteader digging out a stump, when loaded with dex I plodded right past nuances of life in temporary fixations on getting to my desk and writing things down. Which, amazingly, produced pages of a novel faster than when I wasnt taking the stuff. Dex gave me a mental pop, off-the-chart energy upstairs while it played games with the rest of me. Writing proved to be therapy for therapy.

On the topic of mortality, he explained in a written passage, I am now in remission, that terra incognita but better than being off the map(oblivion). He would add, I have not come out of this as any cheerleader for Nietzche: thera are countless preferable ways to strengthen in life without having something trying to kill you.

Facing the reality, he noted, Invariably fatal. Damn. But then, so is life. Its probably not polite to laugh out loud at the writings of a dying man, but I couldnt help myself and I also couldnt help wondering what a pleasure it would have been to take care of him. There was plenty of correspondence in the archive between Ivan and his doctors, but the most striking examples would probably have been overlooked by the uninitiated. The age of electronic medical records and e-mail allow patients unprecedented access to providers.

Like most technology, this chart messaging is both a blessing and a curse. The blessing is that it doesnt take three phone calls to catch a patient at home and tell them about their lab results.

The curse is the dozens of chart messages to return at the end of a busy day. Consequently, as Doig chronicled, brevity is the rule: Everything normal on your labs today, see you in 6 months."

Doig, when in his prime, trying to instill the lessons of history into his work. Here he absorbs the vibe in an abandoned farm house where heart-felt dreams rose, fell part like a heartache and drifted away. Photo by Carol Doig, courtesy MSU Library Doig Archives

The messages from Ivans providers went on for paragraphs, like post cards from your grandmother, and often came close to open displays of affection. All patients are equal, but some are more equal than others.

My day in the Doig archive was followed by an evening at the annual trout lecture hosted by the MSU library and I happened to find the only other Doig nerd who had spent any time with the medical journey files. Todd Wilkinson, the editor of Mountain Journal, shared my fascination with this little known part of Ivan Doigs life and suggested we pursue an event centered around his medical journey.

I couldnt imagine who else would show up to hear about such a niche topic, but didnt want to spoil the glow of our mutual fandom and encouraged him to pursue it. Three months later I found myself sitting in Carol Doigs living room in Seattle.This would be a good time to disclose that I am not a casual Doig fan. Im not a religious person, but I have made two literary pilgrimages in my life. The first was to Arches National Park to find the location of Edward Abbeys trailer from Desert Solitaire and the second was to White Sulfur Springs, Montana to see the place that had figured so prominently in Doig'sThis House of Sky.

Something still haunted me about the archives. Aside from the few pithy quotes above, there wasnt much mention of how Ivan faced his own mortality. How does an author get up every day and write four more novels when he knows hes dying? More importantly, why does he do it?

My practice over the last 20 years was working as a hospitalist. All of my patients were sick enough to be in the hospital and these days you have to be pretty sick to make it through those doors. I had seen hundreds of patients die and typically had end of life conversations with patients and families several times a week. Indeed, I had been on a personal crusade in the last few years to get doctors to talk with their terminally ill patients about their goals for the end of life and had coached other providers about how to do it.

So here was my chance to salvage something of my shattered romantic ideal about writers. Ivan must have had some big epiphany, I thought, that just wasnt there in his writing and my task was to extract it from his widow. I was as if a literary anthropologist on a mission.

It led to having a wonderful day in Seattle, sunny and warm; the Doig living room had a commanding view of Puget Sound. The house was spare and elegant and warm and inviting all at the same time and I got to see Ivans personal desk with his typewriter and his book collection.

Carol was charming and intelligent and well educated and everything you would expect from the spouse of your literary hero. Todd Wilkinson was there and Kenning Arlitsch, Dean of Libraries at MSU, too, and the person responsible for securing the Doig archive. Our conversation flowed easily.

Todd had a flurry of journalistic questions for Carol about Ivan and his writing. I was the final interviewer and my experience told me that it was almost always the wife that was the keeper of the medical history. So I started with some easy logistical questions.

Doig's desk, where he completed five books in eight years, battling through pain, the effects of medicines and a bone marrow transplant. All this and yet critics say these final works contain passages that are among the most incisive and moving of his four-decade long career. Photo by Todd Wilkinson

No, she did not go to all of his medical appointments with him and she didnt even know about the folder where he had kept all of the materials about his illness until after his death. There goes my first assumption.

We walked through the chronology of his illness, his initial diagnosis, the stem cell transplant, chemotherapy, remission, relapse, second line chemotherapy. What was daily life like? How did they deal with telling friends and family since he was not obviously ill until the end? How long was he on hospice? What was it like at the end? I probed, I rephrased, I asked the same question a different way. But there was no profound epiphany.

What she described instead was a guy who got up every day, made breakfast, went to his study and pounded out his words for the day. If he finished a novel on Friday, he started the next on Monday. A literary proletarian if there ever was one.

I have watched plenty of people die in my career, some face it with grace and dignity and resolve and some fight it and raise their fist against the sky until the last breath. What separated those who faced their end well from those who didnt?

Regret. Regret for things they hadnt done or relationships that had soured, but it boiled down to not living life the way they wanted to. My epiphany was that there was no epiphany. Epiphanies are extraneous when you are already living your best life. Ivan Doig was a wonderful writer, husband, friend, and colleague. If it isnt broken, dont fix it.

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A Doctor Plumbs The Depths Of Ivan Doig's Illness And Asks: 'Did He Have An Epiphany?' - Mountain Journal